In the eye of the beholder: the effect of rater variability and different rating scales on QTL mapping.

PubMed

Poland, Jesse A; Nelson, Rebecca J

2011-02-01

The agronomic importance of developing durably resistant cultivars has led to substantial research in the field of quantitative disease resistance (QDR) and, in particular, mapping quantitative trait loci (QTL) for disease resistance. The assessment of QDR is typically conducted by visual estimation of disease severity, which raises concern over the accuracy and precision of visual estimates. Although previous studies have examined the factors affecting the accuracy and precision of visual disease assessment in relation to the true value of disease severity, the impact of this variability on the identification of disease resistance QTL has not been assessed. In this study, the effects of rater variability and rating scales on mapping QTL for northern leaf blight resistance in maize were evaluated in a recombinant inbred line population grown under field conditions. The population of 191 lines was evaluated by 22 different raters using a direct percentage estimate, a 0-to-9 ordinal rating scale, or both. It was found that more experienced raters had higher precision and that using a direct percentage estimation of diseased leaf area produced higher precision than using an ordinal scale. QTL mapping was then conducted using the disease estimates from each rater using stepwise general linear model selection (GLM) and inclusive composite interval mapping (ICIM). For GLM, the same QTL were largely found across raters, though some QTL were only identified by a subset of raters. The magnitudes of estimated allele effects at identified QTL varied drastically, sometimes by as much as threefold. ICIM produced highly consistent results across raters and for the different rating scales in identifying the location of QTL. We conclude that, despite variability between raters, the identification of QTL was largely consistent among raters, particularly when using ICIM. However, care should be taken in estimating QTL allele effects, because this was highly variable and rater dependent.

Identification of weather variables sensitive to dysentery in disease-affected county of China.

PubMed

Liu, Jianing; Wu, Xiaoxu; Li, Chenlu; Xu, Bing; Hu, Luojia; Chen, Jin; Dai, Shuang

2017-01-01

Climate change mainly refers to long-term change in weather variables, and it has significant impact on sustainability and spread of infectious diseases. Among three leading infectious diseases in China, dysentery is exclusively sensitive to climate change. Previous researches on weather variables and dysentery mainly focus on determining correlation between dysentery incidence and weather variables. However, the contribution of each variable to dysentery incidence has been rarely clarified. Therefore, we chose a typical county in epidemic of dysentery as the study area. Based on data of dysentery incidence, weather variables (monthly mean temperature, precipitation, wind speed, relative humidity, absolute humidity, maximum temperature, and minimum temperature) and lagged analysis, we used principal component analysis (PCA) and classification and regression trees (CART) to examine the relationships between the incidence of dysentery and weather variables. Principal component analysis showed that temperature, precipitation, and humidity played a key role in determining transmission of dysentery. We further selected weather variables including minimum temperature, precipitation, and relative humidity based on results of PCA, and used CART to clarify contributions of these three weather variables to dysentery incidence. We found when minimum temperature was at a high level, the high incidence of dysentery occurred if relative humidity or precipitation was at a high level. We compared our results with other studies on dysentery incidence and meteorological factors in areas both in China and abroad, and good agreement has been achieved. Yet, some differences remain for three reasons: not identifying all key weather variables, climate condition difference caused by local factors, and human factors that also affect dysentery incidence. This study hopes to shed light on potential early warnings for dysentery transmission as climate change occurs, and provide a theoretical basis for the control and prevention of dysentery. Copyright © 2016 Elsevier B.V. All rights reserved.

Detecting Microbial Dysbiosis Associated with Pediatric Crohn Disease Despite the High Variability of the Gut Microbiota.

PubMed

Wang, Feng; Kaplan, Jess L; Gold, Benjamin D; Bhasin, Manoj K; Ward, Naomi L; Kellermayer, Richard; Kirschner, Barbara S; Heyman, Melvin B; Dowd, Scot E; Cox, Stephen B; Dogan, Haluk; Steven, Blaire; Ferry, George D; Cohen, Stanley A; Baldassano, Robert N; Moran, Christopher J; Garnett, Elizabeth A; Drake, Lauren; Otu, Hasan H; Mirny, Leonid A; Libermann, Towia A; Winter, Harland S; Korolev, Kirill S

2016-02-02

The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacterial taxa associated with pediatric Crohn disease and can detect significant changes in microbial communities with fewer samples than previous statistical approaches required. We have also substantially improved the accuracy of the diagnosis based on the microbiota from stool samples, and we found that the ecological niche of a microbe predicts its role in Crohn disease. Bacteria typically residing in the lumen of healthy individuals decrease in disease, whereas bacteria typically residing on the mucosa of healthy individuals increase in disease. Our results also show that the associations with Crohn disease are evolutionarily conserved and provide a mutual information-based method to depict dysbiosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Climate Variability, Social and Environmental Factors, and Ross River Virus Transmission: Research Development and Future Research Needs

PubMed Central

Tong, Shilu; Dale, Pat; Nicholls, Neville; Mackenzie, John S.; Wolff, Rodney; McMichael, Anthony J.

2008-01-01

Background Arbovirus diseases have emerged as a global public health concern. However, the impact of climatic, social, and environmental variability on the transmission of arbovirus diseases remains to be determined. Objective Our goal for this study was to provide an overview of research development and future research directions about the interrelationship between climate variability, social and environmental factors, and the transmission of Ross River virus (RRV), the most common and widespread arbovirus disease in Australia. Methods We conducted a systematic literature search on climatic, social, and environmental factors and RRV disease. Potentially relevant studies were identified from a series of electronic searches. Results The body of evidence revealed that the transmission cycles of RRV disease appear to be sensitive to climate and tidal variability. Rainfall, temperature, and high tides were among major determinants of the transmission of RRV disease at the macro level. However, the nature and magnitude of the interrelationship between climate variability, mosquito density, and the transmission of RRV disease varied with geographic area and socioenvironmental condition. Projected anthropogenic global climatic change may result in an increase in RRV infections, and the key determinants of RRV transmission we have identified here may be useful in the development of an early warning system. Conclusions The analysis indicates that there is a complex relationship between climate variability, social and environmental factors, and RRV transmission. Different strategies may be needed for the control and prevention of RRV disease at different levels. These research findings could be used as an additional tool to support decision making in disease control/surveillance and risk management. PMID:19079707

High phenotypic variability in Gerstmann-Sträussler-Scheinker disease.

PubMed

Smid, Jerusa; Studart, Adalberto; Landemberger, Michele Christine; Machado, Cleiton Fagundes; Nóbrega, Paulo Ribeiro; Canedo, Nathalie Henriques Silva; Schultz, Rodrigo Rizek; Naslavsky, Michel Satya; Rosemberg, Sérgio; Kok, Fernando; Chimelli, Leila; Martins, Vilma Regina; Nitrini, Ricardo

2017-06-01

Gerstmann-Sträussler-Scheinker is a genetic prion disease and the most common mutation is p.Pro102Leu. We report clinical, molecular and neuropathological data of seven individuals, belonging to two unrelated Brazilian kindreds, carrying the p.Pro102Leu. Marked differences among patients were observed regarding age at onset, disease duration and clinical presentation. In the first kindred, two patients had rapidly progressive dementia and three exhibited predominantly ataxic phenotypes with variable ages of onset and disease duration. In this family, age at disease onset in the mother and daughter differed by 39 years. In the second kindred, different phenotypes were also reported and earlier ages of onset were associated with 129 heterozygosis. No differences were associated with apoE genotype. In these kindreds, the codon 129 polymorphism could not explain the clinical variability and 129 heterozygosis was associated with earlier disease onset. Neuropathological examination in two patients confirmed the presence of typical plaques and PrPsc immunopositivity.

The socio-economic effects of tropical diseases in Nigeria.

PubMed

Umeh, J C; Amali, O; Umeh, E U

2004-06-01

Urinary schistosomiasis is the most prevalent of the endemic tropical diseases: 48% of the population is afflicted in the study area. The socio-economic, environmental and health-seeking behavioural characteristics of the population are conducive to the spread of urinary schistosomiasis. The attitudes considered include knowledge of what causes the disease and how to control it, attitude toward the disease, care of oneself, hygiene and sanitation. The effect of such social variables as stigmatisation, and environmental variables such as water source is also considered. We find that a unit increase in the hygiene/sanitation index for adult males and adult females lead to a reduction of about 7.3 and 4.0 eggs S. haematobium in 10 ml urine sample, respectively. Thus, simple hygienic activities such as keeping the immediate environment of the household free from human wastes contribute substantially to disease control. Furthermore, prevalence of the disease is higher among males. Losses from work attributed to urinary schistosomiasis are high. Average values of key socio-economic variables-labour flow for land clearing, farm size and cash income-computed for farm families with high urinary schistosomiasis intensity in the sample are 1085 h, 1.4 ha and N 1,432 (US dollars 65) respectively. The corresponding figures for farm families free from the disease are significantly higher: 1325 h, 1.9 ha and N 3,759 (US dollars 171), respectively.

[Pulmonary involvement in connective tissue disease].

PubMed

Bartosiewicz, Małgorzata

2016-01-01

The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.

University of North Carolina Caries Risk Assessment Study: comparisons of high risk prediction, any risk prediction, and any risk etiologic models.

PubMed

Beck, J D; Weintraub, J A; Disney, J A; Graves, R C; Stamm, J W; Kaste, L M; Bohannan, H M

1992-12-01

The purpose of this analysis is to compare three different statistical models for predicting children likely to be at risk of developing dental caries over a 3-yr period. Data are based on 4117 children who participated in the University of North Carolina Caries Risk Assessment Study, a longitudinal study conducted in the Aiken, South Carolina, and Portland, Maine areas. The three models differed with respect to either the types of variables included or the definition of disease outcome. The two "Prediction" models included both risk factor variables thought to cause dental caries and indicator variables that are associated with dental caries, but are not thought to be causal for the disease. The "Etiologic" model included only etiologic factors as variables. A dichotomous outcome measure--none or any 3-yr increment, was used in the "Any Risk Etiologic model" and the "Any Risk Prediction Model". Another outcome, based on a gradient measure of disease, was used in the "High Risk Prediction Model". The variables that are significant in these models vary across grades and sites, but are more consistent among the Etiologic model than the Predictor models. However, among the three sets of models, the Any Risk Prediction Models have the highest sensitivity and positive predictive values, whereas the High Risk Prediction Models have the highest specificity and negative predictive values. Considerations in determining model preference are discussed.

A diagnostic model for chronic hypersensitivity pneumonitis

PubMed Central

Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

2017-01-01

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist’s diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. PMID:27245779

Visit-to-visit and 24-h blood pressure variability: association with endothelial and smooth muscle function in African Americans.

PubMed

Diaz, K M; Veerabhadrappa, P; Kashem, M A; Thakkar, S R; Feairheller, D L; Sturgeon, K M; Ling, C; Williamson, S T; Kretzschmar, J; Lee, H; Grimm, H; Babbitt, D M; Vin, C; Fan, X; Crabbe, D L; Brown, M D

2013-11-01

The purpose of this study was to investigate the association of visit-to-visit and 24-h blood pressure (BP) variability with markers of endothelial injury and vascular function. We recruited 72 African Americans who were non-diabetic, non-smoking and free of cardiovascular (CV) and renal disease. Office BP was measured at three visits and 24-h ambulatory BP monitoring was conducted to measure visit-to-visit and 24-h BP variability, respectively. The 5-min time-course of brachial artery flow-mediated dilation and nitroglycerin-mediated dilation were assessed as measures of endothelial and smooth muscle function. Fasted blood samples were analyzed for circulating endothelial microparticles (EMPs). Significantly lower CD31+CD42- EMPs were found in participants with high visit-to-visit systolic blood pressure (SBP) variability or high 24-h diastolic blood pressure (DBP) variability. Participants with high visit-to-visit DBP variability had significantly lower flow-mediated dilation and higher nitroglycerin-mediated dilation at multiple time-points. When analyzed as continuous variables, 24-h mean arterial pressure variability was inversely associated with CD62+ EMPs; visit-to-visit DBP variability was inversely associated with flow-mediated dilation normalized by smooth muscle function and was positively associated with nitroglycerin-mediated dilation; and 24-h DBP variability was positively associated with nitroglycerin-mediated dilation. All associations were independent of age, gender, body mass index and mean BP. In conclusion, in this cohort of African Americans visit-to-visit and 24-h BP variability were associated with measures of endothelial injury, endothelial function and smooth muscle function. These results suggest that BP variability may influence the pathogenesis of CV disease, in part, through influences on vascular health.

Dutch elm disease control: performance and costs

Treesearch

William N., Jr. Cannon; David P. Worley

1976-01-01

Municipal programs to suppress Dutch elm disease have had highly variable results. Performance as measured by tree mortality was unrelated to control strategies. Costs for control programs were 37 to 76 percent less than costs without control programs in the 15-year time-span of the study. Only those municipalities that conducted a high-performance program could be...

Dutch elm disease control: performance and costs

Treesearch

William N., Jr. Cannon; David P. Worley

1980-01-01

Municipal programs to suppress Dutch elm disease have had highly variable results. Performance as measured by tree mortality was unrelated to control strategies. Costs for control programs were 37 to 76 percent less than costs without control programs in the 15-year time-span of the study. Only those municipalities that conducted a high-performance program could be...

Variability in Cadence During Forced Cycling Predicts Motor Improvement in Individuals With Parkinson’s Disease

PubMed Central

Ridgel, Angela L.; Abdar, Hassan Mohammadi; Alberts, Jay L.; Discenzo, Fred M.; Loparo, Kenneth A.

2014-01-01

Variability in severity and progression of Parkinson’s disease symptoms makes it challenging to design therapy interventions that provide maximal benefit. Previous studies showed that forced cycling, at greater pedaling rates, results in greater improvements in motor function than voluntary cycling. The precise mechanism for differences in function following exercise is unknown. We examined the complexity of biomechanical and physiological features of forced and voluntary cycling and correlated these features to improvements in motor function as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Heart rate, cadence, and power were analyzed using entropy signal processing techniques. Pattern variability in heart rate and power were greater in the voluntary group when compared to forced group. In contrast, variability in cadence was higher during forced cycling. UPDRS Motor III scores predicted from the pattern variability data were highly correlated to measured scores in the forced group. This study shows how time series analysis methods of biomechanical and physiological parameters of exercise can be used to predict improvements in motor function. This knowledge will be important in the development of optimal exercise-based rehabilitation programs for Parkinson’s disease. PMID:23144045

Social gradients in periodontal diseases among adolescents.

PubMed

López, Rodrigo; Fernández, Olaya; Baelum, Vibeke

2006-06-01

To investigate the association between socioeconomic position and periodontal diseases among adolescents. Data were obtained from 9203 Chilean high school students. Clinical examinations included direct recordings of clinical attachment level and the necrotizing ulcerative gingival lesions. Students answered a questionnaire on various dimensions of socioeconomic position. Seven periodontal outcomes were analyzed. Logistic regression analyses were used to identify socioeconomic variables associated with the periodontal outcomes. The occurrence of all periodontal outcomes investigated followed social gradients, and paternal income and parental education were the most influential variables. The study demonstrates the existence of significant social gradients in periodontal diseases already among adolescents. This is worrying, and indicates a new potential for further insight into the mechanisms of periodontal disease causation.

Cardiac autonomic denervation in Parkinson's disease is linked to REM sleep behavior disorder.

PubMed

Postuma, Ronald B; Montplaisir, Jacques; Lanfranchi, Paola; Blais, Hélène; Rompré, Sylvie; Colombo, Roberto; Gagnon, Jean-François

2011-07-01

Recent studies have suggested a close connection between autonomic dysfunction and rapid eye movement sleep behavior disorder, which differs in nature from other early-stage markers of Parkinson's disease. In this study we examined the relationship between rapid eye movement sleep behavior disorder and autonomic dysfunction in Parkinson's disease as measured by cardiac beat-to-beat variability. In 53 patients with Parkinson's disease and 36 controls, electrocardiographic trace from a polysomnogram was assessed for measures of beat-to-beat RR variability including RR-standard deviation and frequency domains (low- and high-frequency components). Results were compared between patients with Parkinson's disease and controls, and between patients with Parkinson's disease with and without rapid eye movement sleep behavior disorder. On numerous cardiac autonomic measures, patients with Parkinson's disease showed clear abnormalities compared with controls. However, these abnormalities were confined only to those patients with associated rapid eye movement sleep behavior; those without were not different than controls. As with other clinical autonomic variables, cardiac autonomic denervation is predominantly associated not with Parkinson's disease itself, but with the presence of rapid eye movement sleep behavior disorder. Copyright © 2011 Movement Disorder Society.

Does health status influence acceptance of illness in patients with chronic respiratory diseases?

PubMed

Kurpas, D; Mroczek, B; Brodowski, J; Urban, M; Nitsch-Osuch, A

2015-01-01

The level of illness acceptance correlates positively with compliance to the doctor's recommendations, and negatively with the frequency and intensity of complications of chronic diseases. The purpose of this study was to determine the influence of the clinical condition on the level of illness acceptance, and to find variables which would have the most profound effect on the level of illness acceptance in patients with chronic respiratory diseases. The study group consisted of 594 adult patients (mean age: 60 ± 15 years) with mixed chronic respiratory diseases, recruited from patients of 136 general practitioners. The average score in the Acceptance of Illness Scale was 26.2 ± 7.6. The low level of illness acceptance was noted in 174 (62.6 %) and high in 46 (16.6 %) patients. Analysis of multiple regressions was used to examine the influence of explanatory variables on the level of illness acceptance. The variables which shaped the level of illness acceptance in our patients included: improvement of health, intensity of symptoms, age, marital status, education level, place of residence, BMI, and the number of chronic diseases. All above mentioned variables should be considered during a design of prevention programs for patients with mixed chronic respiratory diseases.

Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-1-0452 TITLE: Predicting Disease Progression in Scleroderma with Skin and Blood Biomarkers PRINCIPAL INVESTIGATOR: Dr...Predicting Disease Progression in Scleroderma with Skin and Blood 5a. CONTRACT NUMBER Biomarkers 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR...autoimmune disease associated with high morbidity and mortality primarily due to lung disease . There is a large variability in individual patients’ courses

Density-dependent resistance of the gypsy moth, Lymantria dispar, to its nucleopolyhedrovirus

Treesearch

James R. Reilly; Ann E. Hajek

2007-01-01

The processes controlling disease resistance can strongly influence the population dynamics of insect outbreaks. Evidence that disease resistance is density-dependent is accumulating, but the exact form of this relationship is highly variable from species to species.

Validation of an electrophoretic method to detect albuminuria in cats.

PubMed

Ferlizza, Enea; Dondi, Francesco; Andreani, Giulia; Bucci, Diego; Archer, Joy; Isani, Gloria

2017-08-01

Objectives The aims of this study were to validate a semi-automated high-resolution electrophoretic technique to quantify urinary albumin in healthy and diseased cats, and to evaluate its diagnostic performance in cases of proteinuria and renal diseases. Methods Urine samples were collected from 88 cats (healthy; chronic kidney disease [CKD]; lower urinary tract disease [LUTD]; non-urinary tract diseases [OTHER]). Urine samples were routinely analysed and high-resolution electrophoresis (HRE) was performed. Within-assay and between-assay variability, linearity, accuracy, recovery and the lowest detectable and quantifiable bands were calculated. Receiver operating curve (ROC) analysis was also performed. Results All coefficients of variation were <10%, percentage recovery was between 97% and 109% with a high linearity (r = 0.99). HRE allowed the visualisation of a faint band of albumin and a diffused band between alpha and beta zones in healthy cats, while profiles from diseased cats were variable. Albumin (mg/dl) and urine albumin:creatinine ratio (UAC) were significantly ( P <0.05) different between healthy and diseased cats. After ROC analysis, UAC values of 0.035 and 0.074 had a high sensitivity and high specificity, respectively, to classify proteinuria and identify borderline proteinuric cats. Moreover, a UAC of 0.017 had a high sensitivity in distinguishing between healthy and diseased cats. However, UAC was not able to distinguish between renal (CKD) and non-renal diseases (LUTD/OTHER), probably owing to the pathophysiology of CKD in cats, which is characterised by low-grade proteinuria and less glomerular involvement than in dogs. Conclusions and relevance HRE is an accurate and precise method that could be used to measure albuminuria in cats. UAC was useful to correctly classify proteinuria and to discriminate between healthy and diseased cats. HRE might also provide additional information on urine proteins with a profile of all proteins (albumin and globulins) to aid clinicians in the diagnosis of diseases characterised by proteinuria.

Advances in satellite remote sensing of environmental variables for epidemiological applications.

PubMed

Goetz, S J; Prince, S D; Small, J

2000-01-01

Earth-observing satellites have provided an unprecedented view of the land surface but have been exploited relatively little for the measurement of environmental variables of particular relevance to epidemiology. Recent advances in techniques to recover continuous fields of air temperature, humidity, and vapour pressure deficit from remotely sensed observations have significant potential for disease vector monitoring and related epidemiological applications. We report on the development of techniques to map environmental variables with relevance to the prediction of the relative abundance of disease vectors and intermediate hosts. Improvements to current methods of obtaining information on vegetation properties, canopy and surface temperature and soil moisture over large areas are also discussed. Algorithms used to measure these variables incorporate visible, near-infrared and thermal infrared radiation observations derived from time series of satellite-based sensors, focused here primarily but not exclusively on the Advanced Very High Resolution Radiometer (AVHRR) instruments. The variables compare favourably with surface measurements over a broad array of conditions at several study sites, and maps of retrieved variables captured patterns of spatial variability comparable to, and locally more accurate than, spatially interpolated meteorological observations. Application of multi-temporal maps of these variables are discussed in relation to current epidemiological research on the distribution and abundance of some common disease vectors.

Association of monthly frequencies of diverse diseases in the calls to the public emergency service of the city of Buenos Aires during 1999-2004 with meteorological variables and seasons.

PubMed

Alexander, P

2013-01-01

This work aims to study associations between monthly averages of meteorological variables and monthly frequencies of diverse diseases in the calls to the public ambulance emergency service of the city of Buenos Aires during the years 1999-2004. Throughout this time period no changes were made in the classification codes of the illnesses. Heart disease, arrhythmia, heart failure, cardiopulmonary arrest, angina pectoris, psychiatric diseases, stroke, transient ischemic attack, syncope and the total number of calls were analyzed against 11 weather variables and the four seasons. All illnesses exhibited some seasonal behavior, except cardiorespiratory arrest and angina pectoris. The largest frequencies of illnesses that exhibited some association with the meteorological variables used to occur in winter, except the psychiatric cases. Heart failure, stroke, psychiatric diseases and the total number of calls showed significant correlations with the 11 meteorological variables considered, and the largest indices (absolute values above 0.6) were found for the former two pathologies. On the other side, cardiorespiratory arrest and angina pectoris revealed no significant correlations and nearly null indices. Variables associated with temperature were the meteorological proxies with the largest correlations against diseases. Pressure and humidity mostly exhibited positive correlations, which is the opposite of variables related to temperature. Contrary to all other diseases, psychiatric pathologies showed a clear predominance of positive correlations. Finally, the association degree of the medical dataset with recurrent patterns was further evaluated through Fourier analysis, to assess the presence of statistically significant behavior. In the Northern Hemisphere high morbidity and mortality rates in December are usually assigned to diverse factors in relation to the holidays, but such an effect is not observed in the present analysis. There seems to be no clearly preferred meteorological proxy among the different types of temperatures used. It is shown that the amount of occurrences depends mainly on season rather on its strength quantified by temperature.

Association of monthly frequencies of diverse diseases in the calls to the public emergency service of the city of Buenos Aires during 1999-2004 with meteorological variables and seasons

NASA Astrophysics Data System (ADS)

Alexander, P.

2013-01-01

This work aims to study associations between monthly averages of meteorological variables and monthly frequencies of diverse diseases in the calls to the public ambulance emergency service of the city of Buenos Aires during the years 1999-2004. Throughout this time period no changes were made in the classification codes of the illnesses. Heart disease, arrhythmia, heart failure, cardiopulmonary arrest, angina pectoris, psychiatric diseases, stroke, transient ischemic attack, syncope and the total number of calls were analyzed against 11 weather variables and the four seasons. All illnesses exhibited some seasonal behavior, except cardiorespiratory arrest and angina pectoris. The largest frequencies of illnesses that exhibited some association with the meteorological variables used to occur in winter, except the psychiatric cases. Heart failure, stroke, psychiatric diseases and the total number of calls showed significant correlations with the 11 meteorological variables considered, and the largest indices (absolute values above 0.6) were found for the former two pathologies. On the other side, cardiorespiratory arrest and angina pectoris revealed no significant correlations and nearly null indices. Variables associated with temperature were the meteorological proxies with the largest correlations against diseases. Pressure and humidity mostly exhibited positive correlations, which is the opposite of variables related to temperature. Contrary to all other diseases, psychiatric pathologies showed a clear predominance of positive correlations. Finally, the association degree of the medical dataset with recurrent patterns was further evaluated through Fourier analysis, to assess the presence of statistically significant behavior. In the Northern Hemisphere high morbidity and mortality rates in December are usually assigned to diverse factors in relation to the holidays, but such an effect is not observed in the present analysis. There seems to be no clearly preferred meteorological proxy among the different types of temperatures used. It is shown that the amount of occurrences depends mainly on season rather on its strength quantified by temperature.

Alcohol Consumption and Factors Associated with Depressive Symptoms among Older Adults in Mainland China

ERIC Educational Resources Information Center

Liu, Yujun; Xie, Yimeng; Brossoie, Nancy; Roberto, Karen A.; Redican, Kerry J.

2017-01-01

Background: High levels of alcohol consumption have been shown to be related to cardiovascular disease, cancer, diabetes, and other chronic disease and is an important variable in the global burden of disease. Purpose: This study explored the relationship between alcohol consumption and depressive symptoms among older Chinese adults in mainland…

Comparative assessment of lowland and highland Smallholder farmers' vulnerability to climate variability in Ethiopia

NASA Astrophysics Data System (ADS)

Ayal, D. Y., Sr.; Abshare, M. W. M.; Desta, S. D.; Filho, W. L.

2015-12-01

Desalegn Yayeh Ayal P.O.BOX 150129 Addis Ababa University Ethiopia Mobil +251910824784 Abstract Smallholder farmers' near term scenario (2010-2039) vulnerability nature and magnitude was examined using twenty-two exposure, sensitivity and adaptive capacity vulnerability indicators. Assessment of smallholder farmers' vulnerability to climate variability revealed the importance of comprehending exposure, sensitivity and adaptive capacity induces. Due to differences in level of change in rainfall, temperature, drought frequency, their environmental interaction and variations on adaptive capacity the nature and magnitude of smallholder farmers vulnerability to physical, biological and epidemiological challenges of crop and livestock production varied within and across agro-ecologies. Highlanders' sensitive relates with high population density, erosion and crop disease and pest damage occurrence. Whereas lowlanders will be more sensitive to high crop disease and pest damage, provenance of livestock disease, absence of alternative water sources, less diversified agricultural practices. However, with little variations in the magnitude and nature of vulnerability, both highlanders and lowlanders are victims of climate variability and change. Given the ever increasing population, temperature and unpredictable nature of rainfall variability, the study concluded that future adaptation strategies should capitalize on preparing smallholder farmers for both extremes- excess rainfall and flooding on the one hand and severe drought on the other.

Modeling Effects of Temperature, Soil, Moisture, Nutrition and Variety As Determinants of Severity of Pythium Damping-Off and Root Disease in Subterranean Clover

PubMed Central

You, Ming P.; Rensing, Kelly; Renton, Michael; Barbetti, Martin J.

2017-01-01

Subterranean clover (Trifolium subterraneum) is a critical pasture legume in Mediterranean regions of southern Australia and elsewhere, including Mediterranean-type climatic regions in Africa, Asia, Australia, Europe, North America, and South America. Pythium damping-off and root disease caused by Pythium irregulare is a significant threat to subterranean clover in Australia and a study was conducted to define how environmental factors (viz. temperature, soil type, moisture and nutrition) as well as variety, influence the extent of damping-off and root disease as well as subterranean clover productivity under challenge by this pathogen. Relationships were statistically modeled using linear and generalized linear models and boosted regression trees. Modeling found complex relationships between explanatory variables and the extent of Pythium damping-off and root rot. Linear modeling identified high-level (4 or 5-way) significant interactions for each dependent variable (dry shoot and root weight, emergence, tap and lateral root disease index). Furthermore, all explanatory variables (temperature, soil, moisture, nutrition, variety) were found significant as part of some interaction within these models. A significant five-way interaction between all explanatory variables was found for both dry shoot and root dry weights, and a four way interaction between temperature, soil, moisture, and nutrition was found for both tap and lateral root disease index. A second approach to modeling using boosted regression trees provided support for and helped clarify the complex nature of the relationships found in linear models. All explanatory variables showed at least 5% relative influence on each of the five dependent variables. All models indicated differences due to soil type, with the sand-based soil having either higher weights, greater emergence, or lower disease indices; while lowest weights and less emergence, as well as higher disease indices, were found for loam soil and low temperature. There was more severe tap and lateral root rot disease in higher moisture situations. PMID:29184544

Forecasting high-priority infectious disease surveillance regions: a socioeconomic model.

PubMed

Chan, Emily H; Scales, David A; Brewer, Timothy F; Madoff, Lawrence C; Pollack, Marjorie P; Hoen, Anne G; Choden, Tenzin; Brownstein, John S

2013-02-01

Few researchers have assessed the relationships between socioeconomic inequality and infectious disease outbreaks at the population level globally. We use a socioeconomic model to forecast national annual rates of infectious disease outbreaks. We constructed a multivariate mixed-effects Poisson model of the number of times a given country was the origin of an outbreak in a given year. The dataset included 389 outbreaks of international concern reported in the World Health Organization's Disease Outbreak News from 1996 to 2008. The initial full model included 9 socioeconomic variables related to education, poverty, population health, urbanization, health infrastructure, gender equality, communication, transportation, and democracy, and 1 composite index. Population, latitude, and elevation were included as potential confounders. The initial model was pared down to a final model by a backwards elimination procedure. The dependent and independent variables were lagged by 2 years to allow for forecasting future rates. Among the socioeconomic variables tested, the final model included child measles immunization rate and telephone line density. The Democratic Republic of Congo, China, and Brazil were predicted to be at the highest risk for outbreaks in 2010, and Colombia and Indonesia were predicted to have the highest percentage of increase in their risk compared to their average over 1996-2008. Understanding socioeconomic factors could help improve the understanding of outbreak risk. The inclusion of the measles immunization variable suggests that there is a fundamental basis in ensuring adequate public health capacity. Increased vigilance and expanding public health capacity should be prioritized in the projected high-risk regions.

Morbidity among nursing personnel and its association with working conditions and work organization.

PubMed

Vasconcelos, S; Marqueze, E; Gonçalves, L; Lemos, L; Araújo, L; Fischer, F M; Moreno, C R C

2012-01-01

Work organization patterns and working conditions experienced by nursing personnel in the hospital settings may be associated to increased morbidity among these health workers. To estimate the prevalence and factors associated with self-reported diseases among nursing personnel at the emergency hospital in Rio Branco/State of Acre, Brazil. A cross-sectional study was conducted involving 272 participants who answered a questionnaire including sociodemographic characteristics, working conditions, lifestyles, work ability, and a fatigue perception scale. The self-reported diseases in the 12 months prior to data collection were considered the dependent variable. A total of 85.7% of the participants reported one or more diseases in the past 12 months. Most prevalent diseases were: musculoskeletal diseases (37.1%), digestive diseases (28.7%), mental disorders (28.3%), work injuries (27.9%), and respiratory diseases (26.8%). The following significant variables remained in the final model: high work demands (OR 2.69), reported fatigue (OR 3.59), night work (OR 6.55) and being a technician or nursing assistant (OR 4.23). Variables related to working conditions and work organization were associated with the occurrence of reported diseases among nursing professionals. Health promotion measures at work require a comprehensive approach including the working conditions and the work organization.

Genetic basis of inter-individual variability in the effects of exercise on the alleviation of lifestyle-related diseases

PubMed Central

Mori, Masayuki; Higuchi, Keiichi; Sakurai, Akihiro; Tabara, Yasuharu; Miki, Tetsuro; Nose, Hiroshi

2009-01-01

Habitual exercise training, including a high-intensity interval walking programme, improves cardiorespiratory fitness and alleviates lifestyle-related diseases, such as obesity, hypertension and dyslipidaemia. However, the extent of improvement has been shown to differ substantially among individuals for various exercise regimens. A body of literature has demonstrated that gene polymorphisms could account for the inter-individual variability in the improvement of risk factors for lifestyle-related diseases following exercise training. However, the fractions of the variability explained by the polymorphisms are small (∼5%). Also, it is likely that the effects of gene polymorphisms differ with exercise regimens and subject characteristics. These observations suggest the necessity for further studies to exhaustively identify such gene polymorphisms. More importantly, the physiological and molecular genetic mechanisms by which gene polymorphisms interact with exercise to influence the improvements of risk factors for lifestyle-related diseases differentially remain to be clarified. A better understanding of these issues should lead to more effective integration of exercise to optimize the treatment and management of individuals with lifestyle-related diseases. PMID:19736300

Anemia in Patients with Type 2 Diabetes Mellitus

PubMed Central

Barbieri, Jéssica; Fontela, Paula Caitano; Winkelmann, Eliane Roseli; Zimmermann, Carine Eloise Prestes; Sandri, Yana Picinin; Mallet, Emanelle Kerber Viera; Frizzo, Matias Nunes

2015-01-01

The objective of this study was to evaluate the prevalence of anemia in DM2 patients and its correlation with demographic and lifestyle and laboratory variables. This is a descriptive and analytical study of the type of case studies in the urban area of the Ijuí city, registered in programs of the Family Health Strategy, with a total sample of 146 patients with DM2. A semistructured questionnaire with sociodemographic and clinical variables and performed biochemical test was applied. Of the DM2 patients studied, 50 patients had anemia, and it was found that the body mass items and hypertension and hematological variables are significantly associated with anemia of chronic disease. So, the prevalence of anemia is high in patients with DM2. The set of observed changes characterizes the anemia of chronic disease, which affects quality of life of diabetic patients and is associated with disease progression, development, and comorbidities that contribute significantly to increasing the risk of cardiovascular diseases. PMID:26640706

The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program.

PubMed

Grøn, Kathrine Lederballe; Ornbjerg, Lykke Midtbøll; Hetland, Merete Lund; Aslam, Fawad; Khan, Nasim A; Jacobs, Johannes W G; Henrohn, Dan; Rasker, J J; Kauppi, Markku J; Lang, Hui-Chu; Mota, Licia M H; Aggarwal, Amita; Yamanaka, Hisahi; Badsha, Humeira; Gossec, Laure; Cutolo, Maurizio; Ferraccioli, Gianfranco; Gremese, Elisa; Bong Lee, Eun; Inanc, Nevsun; Direskeneli, Haner; Taylor, Peter; Huisman, Margriet; Alten, Rieke; Pohl, Christoph; Oyoo, Omondi; Stropuviene, Sigita; Drosos, Alexandrosos A; Kerzberg, Eduardo; Ancuta, Codorina; Mofti, Ayman; Bergman, Martin; Detert, Jaqueline; Selim, Zaraa I; Abda, Essam A; Rexhepi, Blerta; Sokka, Tuulikki

2014-01-01

The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). Nine thousands eight hundred seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (<24.000 USD) participated in the Quantitative Standard monitoring of Patients with RA (QUEST-RA) study. The prevalence of 31 comorbid conditions, fatigue (0-10 cm visual analogue scale [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability and GDP. Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score was 4.4 (4.8 in low-GDP countries and 3.8 in high-GDP countries, p<0.001). In low-GDP countries 25.4% of the patients had a high level of fatigue (>6.6) compared with 23.0% in high-GDP countries (p<0.001). In univariate analysis, fatigue increased with increasing number of comorbidities, disease activity and disability in both high- and low-GDP countries. In multivariate analysis of all countries, these 3 variables explained 29.4% of the variability, whereas GDP was not significant. Fatigue is a widespread problem associated with high comorbidity burden, disease activity and disability regardless of GDP.

National variability in provision of health services for major long-term conditions in New Zealand (a report from the ABCC NZ study).

PubMed

Connolly, Martin J; Kenealy, Timothy; Barber, P Alan; Carswell, Peter; Clinton, Janet; Dyall, Lorna; Devlin, Gerard; Doughty, Robert N; Kerse, Ngaire; Kolbe, John; Lawrenson, Ross; Moffitt, Allan; Sheridan, Nicolette

2011-10-14

Chronic illness is the leading cause of morbidity, mortality, and inequitable health outcomes in New Zealand. The ABCCNZ Stocktake aimed to identify extent of long-term conditions management evidence-based practices in stroke, cardiovascular disease, chronic obstructive pulmonary disease and congestive heart failure in New Zealand's District Health Boards (DHBs). Eleven 'dimensions' of care for long-term conditions, identified by literature review and confirmed at workshops with long-term conditions professionals, formed the basis of the Stocktake of all 21 DHBs. It comprised two questionnaires: a generic component capturing perceptions of practice; and a disease-specific component assessing service provision. Fifteen DHBs completed all or parts of the questionnaires. Data accrual was completed in July 2008. Although most DHBs had developed long-term conditions management strategies to a moderate degree, there was considerable variability of practice between DHBs. DHBs thought their PHOs had developed strategies in some areas to a low to moderate level, though cardiovascular disease provision rated more highly. Regarding disease-specific services, larger DHBs had greater long-term conditions management provision not only of tertiary services, but of standard care, leadership, self-management, case-management, and audit. There is considerable variability in perceptions of long-term conditions management service provision across DHBs. In many instances variability in actual disease-specific service provision appears to relate to DHB size.

Influence of Education on Disease Activity and Damage in Systemic Lupus Erythematosus: Data From the 1000 Canadian Faces of Lupus.

PubMed

George, Angela; Wong-Pak, Andrew; Peschken, Christine A; Silverman, Earl; Pineau, Christian; Smith, C Douglas; Arbillaga, Hector; Zummer, Michel; Bernatsky, Sasha; Hudson, Marie; Hitchon, Carol; Fortin, Paul R; Nevskaya, Tatiana; Pope, Janet E

2017-01-01

To determine whether socioeconomic status assessed by education is associated with disease activity and the risk of organ damage in systemic lupus erythematosus (SLE). Data from the 1000 Canadian Faces of Lupus, a multicenter database of adult SLE patients, was used to compare education as either low (did not complete high school) or high (completed high school or further) for disease activity and damage. Education was also studied as a continuous variable. The relationships between education and SLE outcomes (any organ damage defined as a Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI] score ≥1, serious organ damage [SDI score ≥3], and end-stage renal disease) were evaluated using logistic regression analyses adjusted for age, sex, race/ethnicity, and disease duration. A total of 562 SLE patients met inclusion criteria (mean age 47 years, 91% female, and mean disease duration of 10 years); 81% had high education. The low education group was twice as likely to be work disabled (30%; P < 0.0001); they had higher disease activity and reduced renal function. Linear regression analysis revealed that low education was significantly associated with higher disease activity at enrollment into the 1000 Canadian Faces of Lupus database, after adjustment for age (at entry and at diagnosis), race/ethnicity, and sex (B 1.255 + 0.507 [SE], β = 0.115, P = 0.014). In our adjusted logistic regression models we were unable to demonstrate significant associations between education and SLE damage. Results did not change when varying the education variable. In this cohort, low education was associated cross-sectionally with higher disease activity and work disability, but not damage. © 2016, American College of Rheumatology.

Intra- and inter-observer agreement on diagnosis of Dupuytren disease, measurements of severity of contracture, and disease extent.

PubMed

Broekstra, Dieuwke C; Lanting, Rosanne; Werker, Paul M N; van den Heuvel, Edwin R

2015-08-01

Dupuytren disease (DD) is a fibrosing disease affecting the palmar aponeurosis, and is mostly treated by surgery based on measurement of severity of flexion contracture of the fingers. Literature concerning the measurement reliability is scarce. This study aimed to determine the intra- and inter-observer agreement of four variables for diagnosing DD, determining severity of contracture, and disease extent. One of them is a new measurement on the area of nodules and cords for measuring the disease extent in early disease stages. An agreement study (n = 54) was performed by two trained investigators. Agreement was calculated per finger, based on an intraclass correlation coefficient (ICC) using a latent variable model on subjects for diagnosis and Tubiana stage. For total passive extension deficit (TPED) and the area of nodules and cords, agreement was calculated with an ICC using a one-way random effects model with subject as random effect. Inter-observer agreement was very good for diagnosing DD (ICC: 95.5%-99.9%) and good to very good for classifying Tubiana stage (ICC: 73.5%-94.9%). Agreements for area and TPED were moderate (middle finger) to very good (ICC: 48.4%-98.6% and 45.0%-99.5%, respectively). Intra-observer agreement was slightly higher on average than inter-observer agreement. Overall, the intra- and inter-observer agreement in diagnosing DD, and determining the severity of flexion contracture is high. Also, the newly introduced variable area of nodules and cords has high intra- and inter-observer agreement, indicating that it is suitable to measure disease extent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cytokines Synergize to Combat Metastatic Neuroblastoma | Center for Cancer Research

Cancer.gov

Neuroblastoma is the most common extracranial solid tumor in children, and clinical outcomes of patients with this disease are quite variable. Prognosis is particularly poor for patients with high-risk tumors (classification based on patients’ age, extent of disease spread, and other biological features).

Voice characteristics in the progression of Parkinson's disease.

PubMed

Holmes, R J; Oates, J M; Phyland, D J; Hughes, A J

2000-01-01

This study examined the acoustic and perceptual voice characteristics of patients with Parkinson's disease according to disease severity. The perceptual and acoustic voice characteristics of 30 patients with early stage PD and 30 patients with later stage PD were compared with data from 30 normal control subjects. Voice recordings consisted of prolongation of the vowel /a/, scale singing, and a 1-min monologue. In comparison with controls and previously published normative data, both early and later stage PD patients' voices were characterized perceptually by limited pitch and loudness variability, breathiness, harshness and reduced loudness. High modal pitch levels also characterized the voices of males in both early and later stages of PD. Acoustically, the voices of both groups of PD patients demonstrated lower mean intensity levels and reduced maximum phonational frequency ranges in comparison with normative data. Although less clear, the present data also suggested that the PD patients' voices were characterized by excess jitter, a high-speaking fundamental frequency for males and a reduced fundamental frequency variability for females. While several of these voice features did not appear to deteriorate with disease progression (i.e. harshness, high modal pitch and speaking fundamental frequency in males, fundamental frequency variability in females, low intensity and jitter), breathiness, monopitch and monoloudness, low loudness and reduced maximum phonational frequency range were all worse in the later stages of PD. Tremor was the sole voice feature which was associated only with later stage PD.

Graph-based impact analysis as a framework for incorporating practitioner knowledge in dairy herd health management.

PubMed

Krieger, M; Schwabenbauer, E-M; Hoischen-Taubner, S; Emanuelson, U; Sundrum, A

2018-03-01

Production diseases in dairy cows are multifactorial, which means they emerge from complex interactions between many different farm variables. Variables with a large impact on production diseases can be identified for groups of farms using statistical models, but these methods cannot be used to identify highly influential variables in individual farms. This, however, is necessary for herd health planning, because farm conditions and associated health problems vary largely between farms. The aim of this study was to rank variables according to their anticipated effect on production diseases on the farm level by applying a graph-based impact analysis on 192 European organic dairy farms. Direct impacts between 13 pre-defined variables were estimated for each farm during a round-table discussion attended by practitioners, that is farmer, veterinarian and herd advisor. Indirect impacts were elaborated through graph analysis taking into account impact strengths. Across farms, factors supposedly exerting the most influence on production diseases were 'feeding', 'hygiene' and 'treatment' (direct impacts), as well as 'knowledge and skills' and 'herd health monitoring' (indirect impacts). Factors strongly influenced by production diseases were 'milk performance', 'financial resources' and 'labour capacity' (directly and indirectly). Ranking of variables on the farm level revealed considerable differences between farms in terms of their most influential and most influenced farm factors. Consequently, very different strategies may be required to reduce production diseases in these farms. The method is based on perceptions and estimations and thus prone to errors. From our point of view, however, this weakness is clearly outweighed by the ability to assess and to analyse farm-specific relationships and thus to complement general knowledge with contextual knowledge. Therefore, we conclude that graph-based impact analysis represents a promising decision support tool for herd health planning. The next steps include testing the method using more specific and problem-oriented variables as well as evaluating its effectiveness.

Exome sequence analysis suggests genetic burden contributes to phenotypic variability and complex neuropathy

PubMed Central

Gonzaga-Jauregui, Claudia; Harel, Tamar; Gambin, Tomasz; Kousi, Maria; Griffin, Laurie B.; Francescatto, Ludmila; Ozes, Burcak; Karaca, Ender; Jhangiani, Shalini; Bainbridge, Matthew N.; Lawson, Kim S.; Pehlivan, Davut; Okamoto, Yuji; Withers, Marjorie; Mancias, Pedro; Slavotinek, Anne; Reitnauer, Pamela J; Goksungur, Meryem T.; Shy, Michael; Crawford, Thomas O.; Koenig, Michel; Willer, Jason; Flores, Brittany N.; Pediaditrakis, Igor; Us, Onder; Wiszniewski, Wojciech; Parman, Yesim; Antonellis, Anthony; Muzny, Donna M.; Katsanis, Nicholas; Battaloglu, Esra; Boerwinkle, Eric; Gibbs, Richard A.; Lupski, James R.

2015-01-01

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ~45% (17/37) of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy associated genes in subjects versus controls; confirmed in a second ethnically discrete neuropathy cohort, suggesting mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HMPVs) and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity. PMID:26257172

Why did bluetongue spread the way it did? Environmental factors influencing the velocity of bluetongue virus serotype 8 epizootic wave in France.

PubMed

Pioz, Maryline; Guis, Hélène; Crespin, Laurent; Gay, Emilie; Calavas, Didier; Durand, Benoît; Abrial, David; Ducrot, Christian

2012-01-01

Understanding where and how fast an infectious disease will spread during an epidemic is critical for its control. However, the task is a challenging one as numerous factors may interact and drive the spread of a disease, specifically when vector-borne diseases are involved. We advocate the use of simultaneous autoregressive models to identify environmental features that significantly impact the velocity of disease spread. We illustrate this approach by exploring several environmental factors influencing the velocity of bluetongue (BT) spread in France during the 2007-2008 epizootic wave to determine which ones were the most important drivers. We used velocities of BT spread estimated in 4,495 municipalities and tested sixteen covariates defining five thematic groups of related variables: elevation, meteorological-related variables, landscape-related variables, host availability, and vaccination. We found that ecological factors associated with vector abundance and activity (elevation and meteorological-related variables), as well as with host availability, were important drivers of the spread of the disease. Specifically, the disease spread more slowly in areas with high elevation and when heavy rainfall associated with extreme temperature events occurred one or two months prior to the first clinical case. Moreover, the density of dairy cattle was correlated negatively with the velocity of BT spread. These findings add substantially to our understanding of BT spread in a temperate climate. Finally, the approach presented in this paper can be used with other infectious diseases, and provides a powerful tool to identify environmental features driving the velocity of disease spread.

Why Did Bluetongue Spread the Way It Did? Environmental Factors Influencing the Velocity of Bluetongue Virus Serotype 8 Epizootic Wave in France

PubMed Central

Pioz, Maryline; Guis, Hélène; Crespin, Laurent; Gay, Emilie; Calavas, Didier; Durand, Benoît; Abrial, David; Ducrot, Christian

2012-01-01

Understanding where and how fast an infectious disease will spread during an epidemic is critical for its control. However, the task is a challenging one as numerous factors may interact and drive the spread of a disease, specifically when vector-borne diseases are involved. We advocate the use of simultaneous autoregressive models to identify environmental features that significantly impact the velocity of disease spread. We illustrate this approach by exploring several environmental factors influencing the velocity of bluetongue (BT) spread in France during the 2007–2008 epizootic wave to determine which ones were the most important drivers. We used velocities of BT spread estimated in 4,495 municipalities and tested sixteen covariates defining five thematic groups of related variables: elevation, meteorological-related variables, landscape-related variables, host availability, and vaccination. We found that ecological factors associated with vector abundance and activity (elevation and meteorological-related variables), as well as with host availability, were important drivers of the spread of the disease. Specifically, the disease spread more slowly in areas with high elevation and when heavy rainfall associated with extreme temperature events occurred one or two months prior to the first clinical case. Moreover, the density of dairy cattle was correlated negatively with the velocity of BT spread. These findings add substantially to our understanding of BT spread in a temperate climate. Finally, the approach presented in this paper can be used with other infectious diseases, and provides a powerful tool to identify environmental features driving the velocity of disease spread. PMID:22916249

Efficacious insect and disease control with laser-guided air-assisted sprayer

USDA-ARS?s Scientific Manuscript database

Efficacy of a newly developed air-assisted variable-rate sprayer was investigated for the control of arthropod pests and plant diseases in six commercial fields. The sprayer was integrated with a high-speed laser scanning sensor, a custom-designed signal processing program, an automatic flow control...

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

PubMed

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

2017-05-26

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

Tumor aggressiveness and patient outcome in cancer of the pancreas assessed by dynamic 18F-FDG PET/CT.

PubMed

Epelbaum, Ron; Frenkel, Alex; Haddad, Riad; Sikorski, Natalia; Strauss, Ludwig G; Israel, Ora; Dimitrakopoulou-Strauss, Antonia

2013-01-01

This study aimed to assess the role of a quantitative dynamic PET model in pancreatic cancer as a potential index of tumor aggressiveness and predictor of survival. Seventy-one patients with (18)F-FDG-avid adenocarcinoma of the pancreas before treatment were recruited, including 27 with localized tumors (11 underwent pancreatectomy, and 16 had localized nonresectable tumors) and 44 with metastatic disease. Dynamic (18)F-FDG PET images were acquired over a 60-min period, followed by a whole-body PET/CT study. Quantitative data measurements were based on a 2-compartment model, and the following variables were calculated: VB (fractional blood volume in target area), K(1) and k(2) (kinetic membrane transport parameters), k(3) and k(4) (intracellular (18)F-FDG phosphorylation and dephosphorylation parameters, respectively), and (18)F-FDG INF (global (18)F-FDG influx). The single significant variable for overall survival (OS) in patients with localized disease was (18)F-FDG INF. Patients with a high (18)F-FDG INF (>0.033 min(-1)) had a median OS of 6 and 5 mo for nonresectable and resected tumors, respectively, versus 15 and 19 mo for a low (18)F-FDG INF in nonresectable and resected tumors, respectively (P < 0.04). In metastatic disease, multivariate analysis found VB, K(1), and k(3) to be significant variables for OS (P < 0.043, <0.031, and <0.009, respectively). Prognostic factors for OS in the entire group of patients that were significant at multivariate analysis were stage of disease, VB, K(1), and (18)F-FDG INF (P < 0.00035, <0.03, <0.024, and <0.008, respectively). Median OS for all patients with a high (18)F-FDG INF, low VB, and high K(1) was 3 mo, as opposed to 14 mo in patients with a low (18)F-FDG INF, high VB, and low K(1) (P < 0.021), irrespective of stage and resectability. Quantitative (18)F-FDG kinetic parameters measured by dynamic PET in newly diagnosed pancreatic cancer correlated with the aggressiveness of disease. The (18)F-FDG INF was the single most significant variable for OS in patients with localized disease, whether resectable or not.

Attention Measures of Accuracy, Variability, and Fatigue Detect Early Response to Donepezil in Alzheimer's Disease: A Randomized, Double-blind, Placebo-Controlled Pilot Trial.

PubMed

Vila-Castelar, Clara; Ly, Jenny J; Kaplan, Lillian; Van Dyk, Kathleen; Berger, Jeffrey T; Macina, Lucy O; Stewart, Jennifer L; Foldi, Nancy S

2018-04-09

Donepezil is widely used to treat Alzheimer's disease (AD), but detecting early response remains challenging for clinicians. Acetylcholine is known to directly modulate attention, particularly under high cognitive conditions, but no studies to date test whether measures of attention under high load can detect early effects of donepezil. We hypothesized that load-dependent attention tasks are sensitive to short-term treatment effects of donepezil, while global and other domain-specific cognitive measures are not. This longitudinal, randomized, double-blind, placebo-controlled pilot trial (ClinicalTrials.gov Identifier: NCT03073876) evaluated 23 participants newly diagnosed with AD initiating de novo donepezil treatment (5 mg). After baseline assessment, participants were randomized into Drug (n = 12) or Placebo (n = 11) groups, and retested after approximately 6 weeks. Cognitive assessment included: (a) attention tasks (Foreperiod Effect, Attentional Blink, and Covert Orienting tasks) measuring processing speed, top-down accuracy, orienting, intra-individual variability, and fatigue; (b) global measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, Dementia Rating Scale); and (c) domain-specific measures (memory, language, visuospatial, and executive function). The Drug but not the Placebo group showed benefits of treatment at high-load measures by preserving top-down accuracy, improving intra-individual variability, and averting fatigue. In contrast, other global or cognitive domain-specific measures could not detect treatment effects over the same treatment interval. The pilot-study suggests that attention measures targeting accuracy, variability, and fatigue under high-load conditions could be sensitive to short-term cholinergic treatment. Given the central role of acetylcholine in attentional function, load-dependent attentional measures may be valuable cognitive markers of early treatment response.

Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with progressive atherosclerosis and incident cardiovascular disease.

PubMed

Pechlaner, Raimund; Willeit, Peter; Summerer, Monika; Santer, Peter; Egger, Georg; Kronenberg, Florian; Demetz, Egon; Weiss, Günter; Tsimikas, Sotirios; Witztum, Joseph L; Willeit, Karin; Iglseder, Bernhard; Paulweber, Bernhard; Kedenko, Lyudmyla; Haun, Margot; Meisinger, Christa; Gieger, Christian; Müller-Nurasyid, Martina; Peters, Annette; Willeit, Johann; Kiechl, Stefan

2015-01-01

The enzyme heme oxygenase-1 (HO-1) exerts cytoprotective effects in response to various cellular stressors. A variable number tandem repeat polymorphism in the HO-1 gene promoter region has previously been linked to cardiovascular disease. We examined this association prospectively in the general population. Incidence of stroke, myocardial infarction, or vascular death was registered between 1995 and 2010 in 812 participants of the Bruneck Study aged 45 to 84 years (49.4% males). Carotid atherosclerosis progression was quantified by high-resolution ultrasound. HO-1 variable number tandem repeat length was determined by polymerase chain reaction. Subjects with ≥32 tandem repeats on both HO-1 alleles compared with the rest of the population (recessive trait) featured substantially increased cardiovascular disease risk (hazard ratio [95% confidence interval], 5.45 [2.39, 12.42]; P<0.0001), enhanced atherosclerosis progression (median difference in atherosclerosis score [interquartile range], 2.1 [0.8, 5.6] versus 0.0 [0.0, 2.2] mm; P=0.0012), and a trend toward higher levels of oxidized phospholipids on apolipoprotein B-100 (median oxidized phospholipids/apolipoprotein B level [interquartile range], 11364 [4160, 18330] versus 4844 [3174, 12284] relative light units; P=0.0554). Increased cardiovascular disease risk in those homozygous for ≥32 repeats was also detected in a pooled analysis of 7848 participants of the Bruneck, SAPHIR, and KORA prospective studies (hazard ratio [95% confidence interval], 3.26 [1.50, 7.33]; P=0.0043). This study found a strong association between the HO-1 variable number tandem repeat polymorphism and cardiovascular disease risk confined to subjects with a high number of repeats on both HO-1 alleles and provides evidence for accelerated atherogenesis and decreased antioxidant defense in this vascular high-risk group. © 2014 American Heart Association, Inc.

Twenty-Year Predictors of Peripheral Arterial Disease Compared With Coronary Heart Disease in the Scottish Heart Health Extended Cohort (SHHEC).

PubMed

Tunstall-Pedoe, Hugh; Peters, Sanne A E; Woodward, Mark; Struthers, Allan D; Belch, Jill J F

2017-09-18

Coronary heart disease and peripheral arterial disease (PAD) affect different vascular territories. Supplementing baseline findings with assays from stored serum, we compared their 20-year predictors. We randomly recruited 15 737 disease-free men and women aged 30 to 75 years across Scotland between 1984 and 1995 and followed them through 2009 for death and hospital diagnoses. Of these, 3098 developed coronary heart disease (19.7%), and 499 PAD (3.2%). Hazard ratios for 45 variables in the Cox model were adjusted for age and sex and for factors in the 2007 ASSIGN cardiovascular risk score. Forty-four of them were entered into parsimonious predictive models, tested by c-statistics and net reclassification improvements. Many hazard ratios diminished with adjustment and parsimonious modeling, leaving significant survivors. The hazard ratios were mostly higher in PAD. New parsimonious models increased the c-statistic and net reclassification improvements over ASSIGN variables alone but varied in their components and ranking. Coronary heart disease and PAD shared 7 of the 9 factors from ASSIGN: age, sex, family history, socioeconomic status, diabetes mellitus, tobacco smoking, and systolic blood pressure (but neither total nor high-density lipoprotein cholesterol); plus 4 new ones: NT-pro-BNP, cotinine, high-sensitivity C-reactive protein, and cystatin-C. The highest ranked hazard ratios for continuous factors in coronary heart disease were those for age, total cholesterol, high-sensitivity troponin, NT-pro-BNP, cotinine, apolipoprotein A, and waist circumference (plus 10 more); in PAD they were age, high-sensitivity C-reactive protein, systolic blood pressure, expired carbon monoxide, cotinine, socioeconomic status, and lipoprotein (a) (plus 5 more). The mixture of shared with disparate determinants for arterial disease in the heart and the legs implies nonidentical pathogenesis: cholesterol dominant in the former, and inflammation (high-sensitivity C-reactive protein, diabetes mellitus, smoking) in the latter. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Forecasting High-Priority Infectious Disease Surveillance Regions: A Socioeconomic Model

PubMed Central

Chan, Emily H.; Scales, David A.; Brewer, Timothy F.; Madoff, Lawrence C.; Pollack, Marjorie P.; Hoen, Anne G.; Choden, Tenzin; Brownstein, John S.

2013-01-01

Background. Few researchers have assessed the relationships between socioeconomic inequality and infectious disease outbreaks at the population level globally. We use a socioeconomic model to forecast national annual rates of infectious disease outbreaks. Methods. We constructed a multivariate mixed-effects Poisson model of the number of times a given country was the origin of an outbreak in a given year. The dataset included 389 outbreaks of international concern reported in the World Health Organization's Disease Outbreak News from 1996 to 2008. The initial full model included 9 socioeconomic variables related to education, poverty, population health, urbanization, health infrastructure, gender equality, communication, transportation, and democracy, and 1 composite index. Population, latitude, and elevation were included as potential confounders. The initial model was pared down to a final model by a backwards elimination procedure. The dependent and independent variables were lagged by 2 years to allow for forecasting future rates. Results. Among the socioeconomic variables tested, the final model included child measles immunization rate and telephone line density. The Democratic Republic of Congo, China, and Brazil were predicted to be at the highest risk for outbreaks in 2010, and Colombia and Indonesia were predicted to have the highest percentage of increase in their risk compared to their average over 1996–2008. Conclusions. Understanding socioeconomic factors could help improve the understanding of outbreak risk. The inclusion of the measles immunization variable suggests that there is a fundamental basis in ensuring adequate public health capacity. Increased vigilance and expanding public health capacity should be prioritized in the projected high-risk regions. PMID:23118271

A diagnostic model for chronic hypersensitivity pneumonitis.

PubMed

Johannson, Kerri A; Elicker, Brett M; Vittinghoff, Eric; Assayag, Deborah; de Boer, Kaïssa; Golden, Jeffrey A; Jones, Kirk D; King, Talmadge E; Koth, Laura L; Lee, Joyce S; Ley, Brett; Wolters, Paul J; Collard, Harold R

2016-10-01

The objective of this study was to develop a diagnostic model that allows for a highly specific diagnosis of chronic hypersensitivity pneumonitis using clinical and radiological variables alone. Chronic hypersensitivity pneumonitis and other interstitial lung disease cases were retrospectively identified from a longitudinal database. High-resolution CT scans were blindly scored for radiographic features (eg, ground-glass opacity, mosaic perfusion) as well as the radiologist's diagnostic impression. Candidate models were developed then evaluated using clinical and radiographic variables and assessed by the cross-validated C-statistic. Forty-four chronic hypersensitivity pneumonitis and eighty other interstitial lung disease cases were identified. Two models were selected based on their statistical performance, clinical applicability and face validity. Key model variables included age, down feather and/or bird exposure, radiographic presence of ground-glass opacity and mosaic perfusion and moderate or high confidence in the radiographic impression of chronic hypersensitivity pneumonitis. Models were internally validated with good performance, and cut-off values were established that resulted in high specificity for a diagnosis of chronic hypersensitivity pneumonitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Heart failure in a woman with SLE, anti-phospholipid syndrome and Fabry’s disease

PubMed Central

Nandagudi, A; Alonzi, D; Butters, TD; Hughes, S; Isenberg, DA

2013-01-01

We describe a female patient with systemic lupus erythematosus (SLE) also diagnosed with Fabry’s disease and anti-phospholipid antibody syndrome (APS). SLE and Fabry’s disease are both systemic diseases with variable clinical presentations. Recent studies have shown a relatively high incidence of late onset Fabry’s disease in female heterozygous individuals, suggesting that this condition could be under-diagnosed. We discuss a possible association between SLE and Fabry’s disease and consider the role of lipid abnormalities in the pathogenesis of SLE. PMID:23864039

Short-Term Effects of Climatic Variables on Hand, Foot, and Mouth Disease in Mainland China, 2008–2013: A Multilevel Spatial Poisson Regression Model Accounting for Overdispersion

PubMed Central

Yang, Fang; Yang, Min; Hu, Yuehua; Zhang, Juying

2016-01-01

Background Hand, Foot, and Mouth Disease (HFMD) is a worldwide infectious disease. In China, many provinces have reported HFMD cases, especially the south and southwest provinces. Many studies have found a strong association between the incidence of HFMD and climatic factors such as temperature, rainfall, and relative humidity. However, few studies have analyzed cluster effects between various geographical units. Methods The nonlinear relationships and lag effects between weekly HFMD cases and climatic variables were estimated for the period of 2008–2013 using a polynomial distributed lag model. The extra-Poisson multilevel spatial polynomial model was used to model the exact relationship between weekly HFMD incidence and climatic variables after considering cluster effects, provincial correlated structure of HFMD incidence and overdispersion. The smoothing spline methods were used to detect threshold effects between climatic factors and HFMD incidence. Results The HFMD incidence spatial heterogeneity distributed among provinces, and the scale measurement of overdispersion was 548.077. After controlling for long-term trends, spatial heterogeneity and overdispersion, temperature was highly associated with HFMD incidence. Weekly average temperature and weekly temperature difference approximate inverse “V” shape and “V” shape relationships associated with HFMD incidence. The lag effects for weekly average temperature and weekly temperature difference were 3 weeks and 2 weeks. High spatial correlated HFMD incidence were detected in northern, central and southern province. Temperature can be used to explain most of variation of HFMD incidence in southern and northeastern provinces. After adjustment for temperature, eastern and Northern provinces still had high variation HFMD incidence. Conclusion We found a relatively strong association between weekly HFMD incidence and weekly average temperature. The association between the HFMD incidence and climatic variables spatial heterogeneity distributed across provinces. Future research should explore the risk factors that cause spatial correlated structure or high variation of HFMD incidence which can be explained by temperature. When analyzing association between HFMD incidence and climatic variables, spatial heterogeneity among provinces should be evaluated. Moreover, the extra-Poisson multilevel model was capable of modeling the association between overdispersion of HFMD incidence and climatic variables. PMID:26808311

Short-Term Effects of Climatic Variables on Hand, Foot, and Mouth Disease in Mainland China, 2008-2013: A Multilevel Spatial Poisson Regression Model Accounting for Overdispersion.

PubMed

Liao, Jiaqiang; Yu, Shicheng; Yang, Fang; Yang, Min; Hu, Yuehua; Zhang, Juying

2016-01-01

Hand, Foot, and Mouth Disease (HFMD) is a worldwide infectious disease. In China, many provinces have reported HFMD cases, especially the south and southwest provinces. Many studies have found a strong association between the incidence of HFMD and climatic factors such as temperature, rainfall, and relative humidity. However, few studies have analyzed cluster effects between various geographical units. The nonlinear relationships and lag effects between weekly HFMD cases and climatic variables were estimated for the period of 2008-2013 using a polynomial distributed lag model. The extra-Poisson multilevel spatial polynomial model was used to model the exact relationship between weekly HFMD incidence and climatic variables after considering cluster effects, provincial correlated structure of HFMD incidence and overdispersion. The smoothing spline methods were used to detect threshold effects between climatic factors and HFMD incidence. The HFMD incidence spatial heterogeneity distributed among provinces, and the scale measurement of overdispersion was 548.077. After controlling for long-term trends, spatial heterogeneity and overdispersion, temperature was highly associated with HFMD incidence. Weekly average temperature and weekly temperature difference approximate inverse "V" shape and "V" shape relationships associated with HFMD incidence. The lag effects for weekly average temperature and weekly temperature difference were 3 weeks and 2 weeks. High spatial correlated HFMD incidence were detected in northern, central and southern province. Temperature can be used to explain most of variation of HFMD incidence in southern and northeastern provinces. After adjustment for temperature, eastern and Northern provinces still had high variation HFMD incidence. We found a relatively strong association between weekly HFMD incidence and weekly average temperature. The association between the HFMD incidence and climatic variables spatial heterogeneity distributed across provinces. Future research should explore the risk factors that cause spatial correlated structure or high variation of HFMD incidence which can be explained by temperature. When analyzing association between HFMD incidence and climatic variables, spatial heterogeneity among provinces should be evaluated. Moreover, the extra-Poisson multilevel model was capable of modeling the association between overdispersion of HFMD incidence and climatic variables.

[A meta-analysis of the variables related to depression in Korean patients with a stroke].

PubMed

Park, Eun Young; Shin, In Soo; Kim, Jung Hee

2012-08-01

The purpose of this study was to use meta-analysis to evaluate the variables related to depression in patients who have had a stroke. The materials of this study were based on 16 variables obtained from 26 recent studies over a span of 10 years which were selected from doctoral dissertations, master's thesis and published articles. Related variables were categorized into sixteen variables and six variable groups which included general characteristics of the patients, disease characteristics, psychological state, physical function, basic needs, and social variables. Also, the classification of six defensive and three risk variables group was based on the negative or positive effect of depression. The quality of life (ES=-.79) and acceptance of disability (ES=-.64) were highly correlated with depression in terms of defensive variables. For risk variables, anxiety (ES=.66), stress (ES=.53) showed high correlation effect size among the risk variables. These findings showed that defensive and risk variables were related to depression among stroke patients. Psychological interventions and improvement in physical functions should be effective in decreasing depression among stroke patients.

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

PubMed

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

2015-08-01

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

Cigarette Smoking Outcomes at Four Years of Follow-Up, Psychosocial Factors, and Reactions to Group Intervention.

ERIC Educational Resources Information Center

Benfari, Robert C.; Eaker, Elaine

1984-01-01

Studied male smokers (N=182) at high risk of coronary heart disease to determine variables that discriminated between successful and nonsuccessful quitters. Analysis revealed that baseline level of smoking, life events, personal security, and selected group process variables were predictive of success or failure in the intervention program.…

Variable regions in Flavobacterium psychrophilum strains identified by comparative genomics: application to selective breeding for cold water disease resistance

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease is one of the most frequent causes of elevated loss in juvenile salmonids, and the development of effective control strategies is a high priority to aquaculturists, management agencies, and conservationists. Since 2005, rainbow trout (Oncorhynchus mykiss) have been bred ...

Neglected diseases and ethnic minorities in the Western Pacific Region exploring the links.

PubMed

Schratz, Alexander; Pineda, Martha Fernanda; Reforma, Liberty G; Fox, Nicole M; Le Anh, Tuan; Tommaso Cavalli-Sforza, L; Henderson, Mackenzie K; Mendoza, Raymond; Utzinger, Jürg; Ehrenberg, John P; Tee, Ah Sian

2010-01-01

Ethnic minority groups (EMGs) are often subject to exclusion, marginalization and poverty. These characteristics render them particularly vulnerable to neglected diseases, a diverse group of diseases that comprise bacteria, ecto-parasites, fungi, helminths and viruses. Despite the health policy relevance, only little is known of the epidemiological profile of neglected diseases among EMGs. We reviewed country data from Australia, Cambodia, Lao People's Democratic Republic, Malaysia, the Philippines and Vietnam and found several overlaps between regions with high proportions of EMG population and high prevalence rates of neglected diseases (infections with soil-transmitted helminths, filarial worms, schistosomes, food-borne trematodes and cestodes). While the links are not always clearly evident and it is impossible to establish correlations among highly aggregated data without control variables-such as environmental factors-there appear indeed to be important linkages between EMGs, socio-economic status and prevalence of neglected diseases. Some determinants under consideration are lack of access to health care and general health status, poverty and social marginalization, as well as education and literacy. Further research is needed to deepen the understanding of these linkages and to determine their public health and socio-economic significance. In particular, there is a need for more data from all countries in the Western Pacific Region that is disaggregated below the provincial level. Selected case studies that incorporate other control variables-such as risk factors from the physical environment-might be useful to inform policy makers about the feasibility of prevention and control interventions that are targeted at high-risk EMGs.

Risk Factors Associated with Disease Recurrence in Patients with Stage III/IV Squamous Cell Carcinoma of the Oral Cavity Treated with Surgery and Postoperative Radiotherapy.

PubMed

Noble, Anisha R; Greskovich, John F; Han, Jaehong; Reddy, Chandana A; Nwizu, Tobenna I; Khan, Mumtaz F; Scharpf, Joseph; Adelstein, David J; Burkey, Brian B; Koyfman, Shlomo A

2016-02-01

The purpose of the present study was to identify variables associated with high risk of failure in patients with locally advanced squamous cell carcinoma of the oral cavity (SCC-OC). This retrospective study included 191 patients with stage III-IVb SCC-OC treated with post-operative radiotherapy (RT) or chemoradiotherapy (CRT) between 1995 and 2013. Disease-free (DFS) and overall survival (OS) were analyzed; variables associated with inferior DFS were identified. Seventy-five patients (39%) recurred. DFS and five-year OS were 52% and 54%, respectively. Poorly differentiated tumors (p=0.03), recurrent tumors (p=0.02) and high nodal ratio (p=0.02) were associated with an increased risk of recurrence. CRT was associated with improved DFS in patients with positive margins and/or extracapsular extension (p=0.021). Tumors that are recurrent, high grade, or have high nodal ratio are at risk of recurrence. Presence of these disease features should be taken into consideration for better risk stratification. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Influence of genetic, biological and pharmacological factors on levodopa dose in Parkinson's disease.

PubMed

Altmann, Vivian; Schumacher-Schuh, Artur F; Rieck, Mariana; Callegari-Jacques, Sidia M; Rieder, Carlos R M; Hutz, Mara H

2016-04-01

Levodopa is first-line treatment of Parkinson's disease motor symptoms but, dose response is highly variable. Therefore, the aim of this study was to determine how much levodopa dose could be explained by biological, pharmacological and genetic factors. A total of 224 Parkinson's disease patients were genotyped for SV2C and SLC6A3 polymorphisms by allelic discrimination assays. Comedication, demographic and clinical data were also assessed. All variables with p < 0.20 were included in a multiple regression analysis for dose prediction. The final model explained 23% of dose variation (F = 11.54; p < 0.000001). Although a good prediction model was obtained, it still needs to be tested in an independent sample to be validated.

Identifying the impact of social determinants of health on disease rates using correlation analysis of area-based summary information.

PubMed

Song, Ruiguang; Hall, H Irene; Harrison, Kathleen McDavid; Sharpe, Tanya Telfair; Lin, Lillian S; Dean, Hazel D

2011-01-01

We developed a statistical tool that brings together standard, accessible, and well-understood analytic approaches and uses area-based information and other publicly available data to identify social determinants of health (SDH) that significantly affect the morbidity of a specific disease. We specified AIDS as the disease of interest and used data from the American Community Survey and the National HIV Surveillance System. Morbidity and socioeconomic variables in the two data systems were linked through geographic areas that can be identified in both systems. Correlation and partial correlation coefficients were used to measure the impact of socioeconomic factors on AIDS diagnosis rates in certain geographic areas. We developed an easily explained approach that can be used by a data analyst with access to publicly available datasets and standard statistical software to identify the impact of SDH. We found that the AIDS diagnosis rate was highly correlated with the distribution of race/ethnicity, population density, and marital status in an area. The impact of poverty, education level, and unemployment depended on other SDH variables. Area-based measures of socioeconomic variables can be used to identify risk factors associated with a disease of interest. When correlation analysis is used to identify risk factors, potential confounding from other variables must be taken into account.

Biologic variability of cardiac troponin I in healthy dogs and dogs with different stages of myxomatous mitral valve disease using standard and high-sensitivity immunoassays.

PubMed

Winter, Randolph L; Saunders, Ashley B; Gordon, Sonya G; Miller, Matthew W; Fosgate, Geoffrey T; Suchodolski, Jan S; Steiner, Jörg M

2017-06-01

Biologic variability (BV) is one aspect of interpreting changes in biomarker concentrations known to be clinically important in people with cardiac disease, but it has not been adequately addressed in dogs so far. The purpose of the study was to determine BV of cardiac troponin I (cTnI) in healthy dogs and dogs with 3 stages of myxomatous mitral valve disease (MMVD). Healthy dogs and dogs with 3 stages of MMVD were prospectively assigned to groups based on comprehensive clinical evaluation using current guidelines. Concentrations of cTnI were measured hourly, daily, and weekly using standard and high-sensitivity immunoassays. Within- (CV I ) and between-subject (CV G ) coefficients of variability, percent reference change value (RCV), and index of individuality (IoI) were calculated. All 10 healthy dogs and 76/112 (68%) of samples from 28 MMVD dogs had cTnI concentrations below the limit of detection (LOD) using a standard sensitivity immunoassay. Only 49/160 (31%) of healthy dog samples and no MMVD samples had cTnI below the high-sensitivity immunoassay LOD. Data analysis for the high-sensitivity immunoassay revealed CV I of 48.1%, CV G of 60.1%, RCV of 134.0%, and IoI of 0.804 in healthy dogs. In MMVD dogs, CV I was 39.6%, CV G was 80.7%, RCV was 110%, and IoI was 0.494. Of all MMVD dogs, those with Stage B2 had the lowest RCV of 91%. Biologic variability affects cTnI concentrations in healthy dogs and dogs with MMVD. Consideration of BV may be clinically relevant when monitoring individual changes in cTnI values, using high-sensitivity immunoassays. © 2017 American Society for Veterinary Clinical Pathology.

Serological markers in inflammatory bowel disease: the pros and cons.

PubMed

Lerner, Aaron; Shoenfeld, Yehuda

2002-02-01

Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease. Among several serological markers anti-Saccharomyces cerevisiae mannan antibodies and perinuclear antineutrophil cytoplasmic autoantibodies are highly disease specific for Crohn's disease and ulcerative colitis, respectively. Combining the two improves their specificity. Sensitivity, however, is still low. Due to lack of standardization and vast interobserver variability, they cannot be used as the only diagnostic criteria but can assist clinicians in diagnosing and categorizing patients with inflammatory bowel disease as well as in helping them to take therapeutic decisions.

Individual and social determinants of multiple chronic disease behavioral risk factors among youth.

PubMed

Alamian, Arsham; Paradis, Gilles

2012-03-22

Behavioral risk factors are known to co-occur among youth, and to increase risks of chronic diseases morbidity and mortality later in life. However, little is known about determinants of multiple chronic disease behavioral risk factors, particularly among youth. Previous studies have been cross-sectional and carried out without a sound theoretical framework. Using longitudinal data (n = 1135) from Cycle 4 (2000-2001), Cycle 5 (2002-2003) and Cycle 6 (2004-2005) of the National Longitudinal Survey of Children and Youth, a nationally representative sample of Canadian children who are followed biennially, the present study examines the influence of a set of conceptually-related individual/social distal variables (variables situated at an intermediate distance from behaviors), and individual/social ultimate variables (variables situated at an utmost distance from behaviors) on the rate of occurrence of multiple behavioral risk factors (physical inactivity, sedentary behavior, tobacco smoking, alcohol drinking, and high body mass index) in a sample of children aged 10-11 years at baseline. Multiple behavioral risk factors were assessed using a multiple risk factor score. All statistical analyses were performed using SAS, version 9.1, and SUDAAN, version 9.01. Multivariate longitudinal Poisson models showed that social distal variables including parental/peer smoking and peer drinking (Log-likelihood ratio (LLR) = 187.86, degrees of freedom (DF) = 8, p < .001), as well as individual distal variables including low self-esteem (LLR = 76.94, DF = 4, p < .001) increased the rate of occurrence of multiple behavioral risk factors. Individual ultimate variables including age, sex, and anxiety (LLR = 9.34, DF = 3, p < .05), as well as social ultimate variables including family socioeconomic status, and family structure (LLR = 10.93, DF = 5, p = .05) contributed minimally to the rate of co-occurrence of behavioral risk factors. The results suggest targeting individual/social distal variables in prevention programs of multiple chronic disease behavioral risk factors among youth.

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

PubMed Central

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

2017-01-01

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

Virulence of Fusarium oxysporum and F. commune to Douglas-fir (Pseudotsuga menziesii) seedlings

Treesearch

J. E. Stewart; Z. Abdo; R. K. Dumroese; N. B. Klopfenstein; M. -S. Kim

2012-01-01

Fusarium species can cause damping-off and root rot of young conifer seedlings, resulting in severe crop and economic losses in forest nurseries. Disease control within tree nurseries is difficult because of the inability to characterize and quantify Fusarium spp. populations with regard to disease potential because of high variability in isolate virulence. Fusarium...

Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

PubMed

van Schouwenburg, Pauline A; Davenport, Emma E; Kienzler, Anne-Kathrin; Marwah, Ishita; Wright, Benjamin; Lucas, Mary; Malinauskas, Tomas; Martin, Hilary C; Lockstone, Helen E; Cazier, Jean-Baptiste; Chapel, Helen M; Knight, Julian C; Patel, Smita Y

2015-10-01

Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways. Copyright © 2015. Published by Elsevier Inc.

Some considerations concerning the challenge of incorporating social variables into epidemiological models of infectious disease transmission.

PubMed

Barnett, Tony; Fournié, Guillaume; Gupta, Sunetra; Seeley, Janet

2015-01-01

Incorporation of 'social' variables into epidemiological models remains a challenge. Too much detail and models cease to be useful; too little and the very notion of infection - a highly social process in human populations - may be considered with little reference to the social. The French sociologist Émile Durkheim proposed that the scientific study of society required identification and study of 'social currents'. Such 'currents' are what we might today describe as 'emergent properties', specifiable variables appertaining to individuals and groups, which represent the perspectives of social actors as they experience the environment in which they live their lives. Here we review the ways in which one particular emergent property, hope, relevant to a range of epidemiological situations, might be used in epidemiological modelling of infectious diseases in human populations. We also indicate how such an approach might be extended to include a range of other potential emergent properties to represent complex social and economic processes bearing on infectious disease transmission.

Potential impacts of climate variability on respiratory morbidity in children, infants, and adults.

PubMed

Souza, Amaury de; Fernandes, Widinei Alves; Pavão, Hamilton Germano; Lastoria, Giancarlo; Albrez, Edilce do Amaral

2012-01-01

To determine whether climate variability influences the number of hospitalizations for respiratory diseases in infants, children, and adults in the city of Campo Grande, Brazil. We used daily data on admissions for respiratory diseases, precipitation, air temperature, humidity, and wind speed for the 2004-2008 period. We calculated the thermal comfort index, effective temperature, and effective temperature with wind speed (wind-chill or heat index) using the meteorological data obtained. Generalized linear models, with Poisson multiple regression, were used in order to predict hospitalizations for respiratory disease. The variables studied were (collectively) found to show relatively high correlation coefficients in relation to hospital admission for pneumonia in children (R² = 68.4%), infants (R² = 71.8%), and adults (R² = 81.8%). Our results indicate a quantitative risk for an increase in the number of hospitalizations of children, infants, and adults, according to the increase or decrease in temperature, humidity, precipitation, wind speed, and thermal comfort index in the city under study.

Improving spatio-temporal model estimation of satellite-derived PM2.5 concentrations: Implications for public health

NASA Astrophysics Data System (ADS)

Barik, M. G.; Al-Hamdan, M. Z.; Crosson, W. L.; Yang, C. A.; Coffield, S. R.

2017-12-01

Satellite-derived environmental data, available in a range of spatio-temporal scales, are contributing to the growing use of health impact assessments of air pollution in the public health sector. Models developed using correlation of Moderate Resolution Imaging Spectrometer (MODIS) Aerosol Optical Depth (AOD) with ground measurements of fine particulate matter less than 2.5 microns (PM2.5) are widely applied to measure PM2.5 spatial and temporal variability. In the public health sector, associations of PM2.5 with respiratory and cardiovascular diseases are often investigated to quantify air quality impacts on these health concerns. In order to improve predictability of PM2.5 estimation using correlation models, we have included meteorological variables, higher-resolution AOD products and instantaneous PM2.5 observations into statistical estimation models. Our results showed that incorporation of high-resolution (1-km) Multi-Angle Implementation of Atmospheric Correction (MAIAC)-generated MODIS AOD, meteorological variables and instantaneous PM2.5 observations improved model performance in various parts of California (CA), USA, where single variable AOD-based models showed relatively weak performance. In this study, we further asked whether these improved models actually would be more successful for exploring associations of public health outcomes with estimated PM2.5. To answer this question, we geospatially investigated model-estimated PM2.5's relationship with respiratory and cardiovascular diseases such as asthma, high blood pressure, coronary heart disease, heart attack and stroke in CA using health data from the Centers for Disease Control and Prevention (CDC)'s Wide-ranging Online Data for Epidemiologic Research (WONDER) and the Behavioral Risk Factor Surveillance System (BRFSS). PM2.5 estimation from these improved models have the potential to improve our understanding of associations between public health concerns and air quality.

Aortic arch calcification detectable on chest X-ray films is associated with plasma diacron-reactive oxygen metabolites in patients with type 2 diabetes but without cardiovascular disease.

PubMed

Watanabe, Kentaro; Ohara, Makoto; Suzuki, Tatsuya; Ouchi, Motoshi; Suzuki, Kazunari; Hashimoto, Masao; Saigusa, Taro; Aoyama, Junya; Nakano, Hiroshi; Oba, Kenzo

2013-01-01

This study aimed to evaluate the relationship between aortic arch calcification (AAC) detectable on chest X-ray films and plasma diacron-reactive oxygen metabolites (d-ROMs) in patients with type 2 diabetes but without cardiovascular disease. Forty-nine patients with type 2 diabetes but without cardiovascular disease were evaluated with chest X-ray examinations and divided into those with AAC (n=26) and those without AAC (n=23). Biochemical variables, including plasma levels of d-ROMS, high-sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) (Lp(a)), were evaluated after an overnight fast. The relationships of AAC with both inflammation and oxidative-stress variables were evaluated. The plasma level of d-ROMs in subjects with AAC was significantly higher than that in subjects without AAC, whereas plasma levels of hsCRP, PAI-1, and Lp(a) in subjects with AAC were higher, but not significantly so, than those in subjects without AAC. Multivariate linear regression analysis with AAC grade as the dependent variable and plasma levels of d-ROMs, hsCRP, PAI-1, or Lp(a) as independent variables demonstrated a significant association of AAC grade with plasma levels of d-ROMs but not with plasma levels of hsCRP, PAI-1, or Lp(a). The plasma level of d-ROMs is associated with AAC in patients with type 2 diabetes but without cardiovascular disease. Hence, the results of the present study suggest that AAC in these patients is strongly associated with oxidative stress. Furthermore, patients with type 2 diabetes and AAC may be at high risk for the development and progression of various diabetic complications induced by oxidative stress.

Classification tree analysis to enhance targeting for follow-up exam of colorectal cancer screening

PubMed Central

2013-01-01

Background Follow-up rate after a fecal occult blood test (FOBT) is low worldwide. In order to increase the follow-up rate, segmentation of the target population has been proposed as a promising strategy, because an intervention can then be tailored toward specific subgroups of the population rather than using one type of intervention for all groups. The aim of this study is to identify subgroups that share the same patterns of characteristics related to follow-up exams after FOBT. Methods The study sample consisted of 143 patients aged 50–69 years who were requested to undergo follow-up exams after FOBT. A classification tree analysis was performed, using the follow-up rate as a dependent variable and sociodemographic variables, psychological variables, past FOBT and follow-up exam, family history of colorectal cancer (CRC), and history of bowel disease as predictive variables. Results The follow-up rate in 143 participants was 74.1% (n = 106). A classification tree analysis identified four subgroups as follows; (1) subgroup with a high degree of fear of CRC, unemployed and with a history of bowel disease (n = 24, 100.0% follow-up rate), (2) subgroup with a high degree of fear of CRC, unemployed and with no history of bowel disease (n = 17, 82.4% follow-up rate), (3) subgroup with a high degree of fear of CRC and employed (n = 24, 66.7% follow-up rate), and (4) subgroup with a low degree of fear of CRC (n = 78, 66.7% follow-up rate). Conclusion The identification of four subgroups with a diverse range of follow-up rates for CRC screening indicates the direction to take in future development of an effective tailored intervention strategy. PMID:24112563

Crystal Structure of Neurotropism-Associated Variable Surface Protein 1 (VSP1) of Borrelia Turicatae

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

Lawson,C.; Yung, B.; Barbour, A.

2006-01-01

Vsp surface lipoproteins are serotype-defining antigens of relapsing fever spirochetes that undergo multiphasic antigenic variation to allow bacterial persistence in spite of an immune response. Two isogenic serotypes of Borrelia turicatae strain Oz1 differ in their Vsp sequences and in disease manifestations in infected mice: Vsp1 is associated with the selection of a neurological niche, while Vsp2 is associated with blood and skin infection. We report here crystal structures of the Vsp1 dimer at 2.7 and 2.2 Angstroms. The structures confirm that relapsing fever Vsp proteins share a common helical fold with OspCs of Lyme disease-causing Borrelia. The fold featuresmore » an inner stem formed by highly conserved N and C termini and an outer 'dome' formed by the variable central residues. Both Vsp1 and OspC structures possess small water-filled cavities, or pockets, that are lined largely by variable residues and are thus highly variable in shape. These features appear to signify tolerance of the Vsp-OspC fold for imperfect packing of residues at its antigenic surface. Structural comparison of Vsp1 with a homology model for Vsp2 suggests that observed differences in disease manifestation may arise in part from distinct differences in electrostatic surface properties; additional predicted positively charged surface patches on Vsp2 compared to Vsp1 may be sufficient to explain the relative propensity of Vsp2 to bind to acidic glycosaminoglycans.« less

Meteorological Influences on the Seasonality of Lyme Disease in the United States

PubMed Central

Moore, Sean M.; Eisen, Rebecca J.; Monaghan, Andrew; Mead, Paul

2014-01-01

Lyme disease (Borrelia burgdorferi infection) is the most common vector-transmitted disease in the United States. The majority of human Lyme disease (LD) cases occur in the summer months, but the timing of the peak occurrence varies geographically and from year to year. We calculated the beginning, peak, end, and duration of the main LD season in 12 highly endemic states from 1992 to 2007 and then examined the association between the timing of these seasonal variables and several meteorological variables. An earlier beginning to the LD season was positively associated with higher cumulative growing degree days through Week 20, lower cumulative precipitation, a lower saturation deficit, and proximity to the Atlantic coast. The timing of the peak and duration of the LD season were also associated with cumulative growing degree days, saturation deficit, and cumulative precipitation, but no meteorological predictors adequately explained the timing of the end of the LD season. PMID:24470565

[Body composition and heart rate variability in patients with chronic obstructive pulmonary disease pulmonary rehabilitation candidates].

PubMed

Curilem Gatica, Cristian; Almagià Flores, Atilio; Yuing Farías, Tuillang; Rodríguez Rodríguez, Fernando

2014-07-01

Body composition is a non-invasive method, which gives us information about the distribution of tissues in the body structure, it is also an indicator of the risk of mortality in patients with chronic obstructive pulmonary disease. The heart rate variability is a technique that gives us information of autonomic physiological condition, being recognized as an indicator which is decreased in a number of diseases. The purpose of this study was to assess body composition and heart rate variability. The methodology used is that of Debora Kerr (1988) endorsed by the International Society for advances in Cineantropometría for body composition and heart rate variability of the guidelines described by the American Heart Association (1996). Roscraff equipment, caliper Slimguide and watch Polar RS 800CX was used. , BMI 26.7 ± 3.9 kg / m²; Muscle Mass 26.1 ± 6.3 kg ; Bone Mass 1.3 kg ± 8.1 76 ± 9.9 years Age : 14 candidates for pulmonary rehabilitation patients were evaluated , Adipose mass 16.4 ± 3.6 kg ; FEV1 54 ± 14%. Increased waist circumference and waist hip ratio was associated with a lower overall heart rate variability. The bone component was positively related to the variability of heart rate and patients with higher forced expiratory volume in one second had lower high frequency component in heart rate variability. In these patients, the heart rate variability is reduced globally and is associated with cardiovascular risk parameters. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Antibacterial Activity of Hawaiian Corals: Possible Protection from Disease?

NASA Astrophysics Data System (ADS)

Gochfeld, D. J.; Aeby, G. S.; Miller, J. D.

2006-12-01

Reports of coral diseases in the Caribbean have appeared with increasing frequency over the past two decades; however, records of coral diseases in the Pacific have lagged far behind. Recent surveys of coral disease in the Hawaiian Islands indicate relatively low, but consistent, levels of disease throughout the inhabited Main and uninhabited Northwestern Hawaiian Islands, and demonstrate variation in levels of disease among the major genera of Hawaiian corals. Although little is known about immune defense to disease in corals, one potential mechanism of defense is the production of antimicrobial compounds that protect corals from pathogens. A preliminary survey of antibacterial chemical defenses among three dominant species of Hawaiian corals was undertaken. Crude aqueous extracts of Porites lobata, Pocillopora meandrina and Montipora capitata were tested against nine strains of bacteria in a growth inhibition assay. Inhibitory extracts were further tested to determine whether their effects were cytostatic or cytotoxic. The bacteria selected included known coral pathogens, potential marine pathogens found in human waste and strains previously identified from the surfaces of Hawaiian corals. Extracts from all three species of coral exhibited a high degree of antibacterial activity, but also a high degree of selectivity against different bacterial strains. In addition, some extracts were stimulatory to some bacteria. In addition to interspecific variability, extracts also exhibited intraspecific variability, both within and between sites. Hawaiian corals have significant antibacterial activity, which may explain the relatively low prevalence of disease in these corals; however, further characterization of pathogens specifically responsible for disease in Hawaiian corals is necessary before we can conclude that antibacterial activity protects Hawaiian corals from disease.

Real-time forecasts of dengue epidemics

NASA Astrophysics Data System (ADS)

Yamana, T. K.; Shaman, J. L.

2015-12-01

Dengue is a mosquito-borne viral disease prevalent in the tropics and subtropics, with an estimated 2.5 billion people at risk of transmission. In many areas with endemic dengue, disease transmission is seasonal but prone to high inter-annual variability with occasional severe epidemics. Predicting and preparing for periods of higher than average transmission is a significant public health challenge. Here we present a model of dengue transmission and a framework for optimizing model simulations with real-time observational data of dengue cases and environmental variables in order to generate ensemble-based forecasts of the timing and severity of disease outbreaks. The model-inference system is validated using synthetic data and dengue outbreak records. Retrospective forecasts are generated for a number of locations and the accuracy of these forecasts is quantified.

Topography as a contextual variable in infectious disease transmission.

PubMed

Montoya, Isaac D

2004-01-01

This paper examines whether or not topography is a contextual variable that indirectly influences the transmission of infectious diseases. Age, gender, race/ethnicity, education level, economic status, injection drug use, and high-risk sexual behavior are known to influence infectious diseases transmission, but the effects of topography are often overlooked. A sample of 395 drug users were chosen from census tracts based upon a target profile of drug use behavior and demographics for the city of Houston. HIV was chosen as the infectious disease used to test this hypothesis. Residents of 16 census tracts in Houston, Texas participated in this study. The findings revealed that census tracts that were 'isolated' by topographic barriers, such as bayous, parks, railroad tracks, railway yards, major thoroughfares, freeways, and unique street grids had fewer cases of HIV than census tracks that were more accessible to thru-traffic. The research findings suggest that future research studies should consider topography as being contextually related to infectious disease transmission.

Recognizing the importance of chronic disease in driving healthcare expenditure in Tanzania: analysis of panel data from 1991 to 2010.

PubMed

Counts, Christopher J; Skordis-Worrall, Jolene

2016-05-01

 Despite the growing chronic disease burden in low- and middle-income countries, there are significant gaps in our understanding of the financial impact of these illnesses on households. As countries make progress towards universal health coverage, specific information is needed about how chronic disease care drives health expenditure over time, and how this spending differs from spending on acute disease care.  A 19-year panel dataset was constructed using data from the Kagera Health and Development Surveys. Health expenditure was modelled using multilevel regression for three different sub-populations of households: (1) all households that spent on healthcare, (2) households affected by chronic disease and (3) households affected by acute disease. Explanatory variables were identified from a review of the health expenditure literature, and all variables were analysed descriptively.  Households affected by chronic disease spent 22% more on healthcare than unaffected households. Catastrophic expenditure and zero expenditure are both common in chronic disease-affected households. Expenditure predictors were different between households affected by chronic disease and those unaffected. Expenditure over time is highly heterogeneous and household-dependent.  The financial burden of healthcare is greater for households affected by chronic disease than those unaffected. Households appear unable to sustain high levels of expenditure over time, likely resulting in both irregular chronic disease treatment and impoverishment. The Tanzanian government's current efforts to develop a National Health Financing Strategy present an important opportunity to prioritize policies that promote the long-term financial protection of households by preventing the catastrophic consequences of chronic disease care payments. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Predictors of outcome and methodological issues in children with acute lymphoblastic leukaemia in El Salvador.

PubMed

Bonilla, Miguel; Gupta, Sumit; Vasquez, Roberto; Fuentes, Soad L; deReyes, Gladis; Ribeiro, Raul; Sung, Lillian

2010-12-01

Most children with cancer live in low-income countries (LICs) where risk factors in paediatric acute lymphoblastic leukaemia (ALL) developed in high-income countries may not apply. We describe predictors of survival for children in El Salvador with ALL. We included patients <16 years diagnosed with ALL between January 2001 and July 2007 treated with the El Salvador-Guatemala-Honduras II protocol. Demographic, disease-related, socioeconomic and nutritional variables were examined as potential predictors of event-free survival (EFS) and overall survival (OS). 260/443 patients (58.7%) were classified as standard risk. Standard- and high-risk 5-year EFS were 56.3 ± 4.5% and 48.6 ± 5.5%; 5-year OS were 77.7 ± 3.8% and 61.9 ± 5.8%, respectively. Among standard-risk children, socioeconomic variables such as higher monthly income (hazard ratio [HR] per $100 = 0.84 [95% confidence interval (CI) 0.70-0.99; P=0.04]) and parental secondary education (HR = 0.49, 95% CI 0.29-0.84; P = 0.01) were associated with better EFS. Among high-risk children, higher initial white blood cell (HR per 10×10(9)/L = 1.03, 95% CI 1.02-1.05; P<0.001) predicted worse EFS; socioeconomic variables were not predictive. The difference in EFS and OS appeared related to overestimating OS secondary to poor follow-up after abandonment/relapse. Socioeconomic variables predicted worse EFS in standard-risk children while disease-related variables were predictive in high-risk patients. Further studies should delineate pathways through which socioeconomic status affects EFS in order to design effective interventions. EFS should be the primary outcome in LIC studies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Characterization of class II β chain major histocompatibility complex genes in a family of Hawaiian honeycreepers: 'amakihi (Hemignathus virens).

PubMed

Jarvi, Susan I; Bianchi, Kiara R; Farias, Margaret Em; Txakeeyang, Ann; McFarland, Thomas; Belcaid, Mahdi; Asano, Ashley

2016-07-01

Hawaiian honeycreepers (Drepanidinae) have evolved in the absence of mosquitoes for over five million years. Through human activity, mosquitoes were introduced to the Hawaiian archipelago less than 200 years ago. Mosquito-vectored diseases such as avian malaria caused by Plasmodium relictum and Avipoxviruses have greatly impacted these vulnerable species. Susceptibility to these diseases is variable among and within species. Due to their function in adaptive immunity, the role of major histocompatibility complex genes (Mhc) in disease susceptibility is under investigation. In this study, we evaluate gene organization and levels of diversity of Mhc class II β chain genes (exon 2) in a captive-reared family of Hawaii 'amakihi (Hemignathus virens). A total of 233 sequences (173 bp) were obtained by PCR+1 amplification and cloning, and 5720 sequences were generated by Roche 454 pyrosequencing. We report a total of 17 alleles originating from a minimum of 14 distinct loci. We detected three linkage groups that appear to represent three distinct haplotypes. Phylogenetic analysis revealed one variable cluster resembling classical Mhc sequences (DAB) and one highly conserved, low variability cluster resembling non-classical Mhc sequences (DBB). High net evolutionary divergence values between DAB and DBB resemble that seen between chicken BLB system and YLB system genes. High amino acid identity among non-classical alleles from 12 species of passerines (DBB) and four species of Galliformes (YLB) was found, suggesting that these non-classical passerine sequences may be related to the Galliforme YLB sequences.

Cluster Analysis of Clinical Data Identifies Fibromyalgia Subgroups

PubMed Central

Docampo, Elisa; Collado, Antonio; Escaramís, Geòrgia; Carbonell, Jordi; Rivera, Javier; Vidal, Javier; Alegre, José

2013-01-01

Introduction Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. Material and Methods 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. Results Variables clustered into three independent dimensions: “symptomatology”, “comorbidities” and “clinical scales”. Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. Conclusions We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment. PMID:24098674

Variable high pressure processing sensitivities for GII human noroviruses

USDA-ARS?s Scientific Manuscript database

Human norovirus (HuNoV) is the leading cause of foodborne diseases worldwide. High pressure processing (HPP) is one of the most promising non-thermal technologies for decontamination of viral pathogens in foods. However, the survival of HuNoVs by HPP is poorly understood because these viruses cann...

Site-specific management of cotton root rot using airborne and high resolution satellite imagery and variable rate technology

USDA-ARS?s Scientific Manuscript database

Cotton root rot is a century-old cotton disease that can now be effectively controlled with Topguard Terra Fungicide. As this disease tends to occur in the same general areas within fields in recurring years, site-specific application of the fungicide only to the infested areas can be more effective...

'Ome' on the range: update on high-altitude acclimatization/adaptation and disease.

PubMed

Luo, Yongjun; Wang, Yuxiao; Lu, Hongxiang; Gao, Yuqi

2014-11-01

The main physiological challenge in high-altitude plateau environments is hypoxia. When people living in a plain environment migrate to the plateau, they face the threat of hypoxia. Most people can acclimatize to high altitudes; the acclimatization process mainly consists of short-term hyperventilation and long-term compensation by increased oxygen uptake, transport, and use due to increased red blood cell mass, myoglobin, and mitochondria. If individuals cannot acclimatize to high altitude, they may suffer from a high-altitude disease, such as acute mountain disease (AMS), high-altitude pulmonary edema (HAPE), high-altitude cerebral edema (HACE) or chronic mountain sickness (CMS). Because some individuals are more susceptible to high altitude diseases than others, the incidence of these high-altitude diseases is variable and cannot be predicted. Studying "omes" using genomics, proteomics, metabolomics, transcriptomics, lipidomics, immunomics, glycomics and RNomics can help us understand the factors that mediate susceptibility to high altitude illnesses. Moreover, analysis of the "omes" using a systems biology approach may provide a greater understanding of high-altitude illness pathogenesis and improve the efficiency of the diagnosis and treatment of high-altitude illnesses in the future. Below, we summarize the current literature regarding the role of "omes" in high-altitude acclimatization/adaptation and disease and discuss key research gaps to better understand the contribution of "omes" to high-altitude illness susceptibility.

Mapping of Variable DNA Methylation Across Multiple Cell Types Defines a Dynamic Regulatory Landscape of the Human Genome.

PubMed

Gu, Junchen; Stevens, Michael; Xing, Xiaoyun; Li, Daofeng; Zhang, Bo; Payton, Jacqueline E; Oltz, Eugene M; Jarvis, James N; Jiang, Kaiyu; Cicero, Theodore; Costello, Joseph F; Wang, Ting

2016-04-07

DNA methylation is an important epigenetic modification involved in many biological processes and diseases. Many studies have mapped DNA methylation changes associated with embryogenesis, cell differentiation, and cancer at a genome-wide scale. Our understanding of genome-wide DNA methylation changes in a developmental or disease-related context has been steadily growing. However, the investigation of which CpGs are variably methylated in different normal cell or tissue types is still limited. Here, we present an in-depth analysis of 54 single-CpG-resolution DNA methylomes of normal human cell types by integrating high-throughput sequencing-based methylation data. We found that the ratio of methylated to unmethylated CpGs is relatively constant regardless of cell type. However, which CpGs made up the unmethylated complement was cell-type specific. We categorized the 26,000,000 human autosomal CpGs based on their methylation levels across multiple cell types to identify variably methylated CpGs and found that 22.6% exhibited variable DNA methylation. These variably methylated CpGs formed 660,000 variably methylated regions (VMRs), encompassing 11% of the genome. By integrating a multitude of genomic data, we found that VMRs enrich for histone modifications indicative of enhancers, suggesting their role as regulatory elements marking cell type specificity. VMRs enriched for transcription factor binding sites in a tissue-dependent manner. Importantly, they enriched for GWAS variants, suggesting that VMRs could potentially be implicated in disease and complex traits. Taken together, our results highlight the link between CpG methylation variation, genetic variation, and disease risk for many human cell types. Copyright © 2016 Gu et al.

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

PubMed

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

2009-11-01

To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries.

Independence screening for high dimensional nonlinear additive ODE models with applications to dynamic gene regulatory networks.

PubMed

Xue, Hongqi; Wu, Shuang; Wu, Yichao; Ramirez Idarraga, Juan C; Wu, Hulin

2018-05-02

Mechanism-driven low-dimensional ordinary differential equation (ODE) models are often used to model viral dynamics at cellular levels and epidemics of infectious diseases. However, low-dimensional mechanism-based ODE models are limited for modeling infectious diseases at molecular levels such as transcriptomic or proteomic levels, which is critical to understand pathogenesis of diseases. Although linear ODE models have been proposed for gene regulatory networks (GRNs), nonlinear regulations are common in GRNs. The reconstruction of large-scale nonlinear networks from time-course gene expression data remains an unresolved issue. Here, we use high-dimensional nonlinear additive ODEs to model GRNs and propose a 4-step procedure to efficiently perform variable selection for nonlinear ODEs. To tackle the challenge of high dimensionality, we couple the 2-stage smoothing-based estimation method for ODEs and a nonlinear independence screening method to perform variable selection for the nonlinear ODE models. We have shown that our method possesses the sure screening property and it can handle problems with non-polynomial dimensionality. Numerical performance of the proposed method is illustrated with simulated data and a real data example for identifying the dynamic GRN of Saccharomyces cerevisiae. Copyright © 2018 John Wiley & Sons, Ltd.

Long-term cortisol measures predict Alzheimer disease risk.

PubMed

Ennis, Gilda E; An, Yang; Resnick, Susan M; Ferrucci, Luigi; O'Brien, Richard J; Moffat, Scott D

2017-01-24

To examine whether long-term measures of cortisol predict Alzheimer disease (AD) risk. We used a prospective longitudinal design to examine whether cortisol dysregulation was related to AD risk. Participants were from the Baltimore Longitudinal Study of Aging (BLSA) and submitted multiple 24-hour urine samples over an average interval of 10.56 years. Urinary free cortisol (UFC) and creatinine (Cr) were measured, and a UFC/Cr ratio was calculated to standardize UFC. To measure cortisol regulation, we used within-person UFC/Cr level (i.e., within-person mean), change in UFC/Cr over time (i.e., within-person slope), and UFC/Cr variability (i.e., within-person coefficient of variation). Cox regression was used to assess whether UFC/Cr measures predicted AD risk. UFC/Cr level and UFC/Cr variability, but not UFC/Cr slope, were significant predictors of AD risk an average of 2.9 years before AD onset. Elevated UFC/Cr level and elevated UFC/Cr variability were related to a 1.31- and 1.38-times increase in AD risk, respectively. In a sensitivity analysis, increased UFC/Cr level and increased UFC/Cr variability predicted increased AD risk an average of 6 years before AD onset. Cortisol dysregulation as manifested by high UFC/Cr level and high UFC/Cr variability may modulate the downstream clinical expression of AD pathology or be a preclinical marker of AD. © 2016 American Academy of Neurology.

Characteristics of seroconversion and implications for diagnosis of post-treatment Lyme disease syndrome: acute and convalescent serology among a prospective cohort of early Lyme disease patients.

PubMed

Rebman, Alison W; Crowder, Lauren A; Kirkpatrick, Allison; Aucott, John N

2015-03-01

Two-tier serology is often used to confirm a diagnosis of Lyme disease. One hundred and four patients with physician diagnosed erythema migrans rashes had blood samples taken before and after 3 weeks of doxycycline treatment for early Lyme disease. Acute and convalescent serologies for Borrelia burgdorferi were interpreted according to the 2-tier antibody testing criteria proposed by the Centers for Disease Control and Prevention. Serostatus was compared across several clinical and demographic variables both pre- and post-treatment. Forty-one patients (39.4%) were seronegative both before and after treatment. The majority of seropositive individuals on both acute and convalescent serology had a positive IgM western blot and a negative IgG western blot. IgG seroconversion on western blot was infrequent. Among the baseline variables included in the analysis, disseminated lesions (p < 0.0001), a longer duration of illness (p < 0.0001), and a higher number of reported symptoms (p = 0.004) were highly significantly associated with positive final serostatus, while male sex (p = 0.05) was borderline significant. This variability, and the lack of seroconversion in a subset of patients, highlights the limitations of using serology alone in identifying early Lyme disease. Furthermore, these findings underline the difficulty for rheumatologists in identifying a prior exposure to Lyme disease in caring for patients with medically unexplained symptoms or fibromyalgia-like syndromes.

High coffee intake is associated with lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity.

PubMed

Gutiérrez-Grobe, Ylse; Chávez-Tapia, Norberto; Sánchez-Valle, Vicente; Gavilanes-Espinar, Juan Gabriel; Ponciano-Rodríguez, Guadalupe; Uribe, Misael; Méndez-Sánchez, Nahum

2012-01-01

Some phytochemicals present in coffee have a potential antioxidant role which seems to protect the human body against cardiovascular diseases, liver disease and malignancies. Nonalcoholic fatty liver disease is a common disease with limited therapeutic options. This study investigated the antioxidant effect of coffee by measuring antioxidant enzymes and lipid peroxidation markers in patients with nonalcoholic fatty liver disease. We performed a case-control study at the University Hospital, Mexico City. Anthropometric, metabolic, dietary and biochemical variables of all patients were determined and compared. The presence of nonalcoholic fatty liver disease was established by ultrasonography. All patients completed a dietary questionnaire in order to determine their of coffee consumption. Catalase, superoxide dismutase and thiobarbituric acid reactive substances were measured in all of the patients. Seventy-three subjects with and 57 without nonalcoholic fatty liver disease were included. Patients with nonalcoholic fatty liver disease had significantly higher body mass index, blood glucose, homeostasis model of assessment-insulin resistance and insulin values in comparison to patients without nonalcoholic fatty liver disease. On the one hand, there was a significant difference in coffee intake between the groups (p < 0.05, for all comparisons). There was no significant difference between groups in catalase (0.39 ± 0.74 vs. 0.28 ± 0.69 nM/min/mL), superoxide dismutase (5.4 ± 3.45 vs. 4.7 ± 2.1 U/mL) or thiobarbituric acid-reactive substances (4.05 ± 1.87 vs. 3.94 ± 1.59 µM/mL). A high intake of coffee has a protective effect against nonalcoholic fatty liver disease however there was no significant difference in the antioxidant variables analyzed.

[Dyslipidaemia and atherogenic risk in patients with systemic lupus erythematosus].

PubMed

Batún Garrido, José Antonio de Jesús; Radillo Alba, Hugo Alberto; Hernández Núñez, Éufrates; Olán, Francisco

2016-07-15

Dyslipidaemia is a common comorbidity in patients with systemic lupus erythematosus. Fifty-one patients were included. Variables associated with the disease and the drugs used were recorded. Atherogenic risk was calculated. Chi square was used for categorical variables. ANOVA was performed and a logistic regression model to determine the association of the variables with the presence of dyslipidaemia. A percentage of 68.6 had dyslipidaemia. A significant difference between the presence of dyslipidaemia and activity index measured by SLEDAI was found, the presence of lupus nephritis, use of prednisone≥20mg/day, evolution of the disease<3 years. Significance between the absence of dyslipidaemia and use of hydroxychloroquine was found. SLEDAI≥4 and the use of prednisone≥20mg/day were independently associated with the presence of dyslipidaemia. The average of Castelli rate was 5.02, the Kannel index was 2.97 and triglyceride/HDL-C ratio was 5.24. Patients with systemic lupus erythematosus have a high prevalence of dyslipidaemia and a high atherogenic rate, which increases cardiovascular risk significantly. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Myxomatosis in wild rabbit: design of control programs in Mediterranean ecosystems.

PubMed

García-Bocanegra, Ignacio; Astorga, Rafael Jesús; Napp, Sebastián; Casal, Jordi; Huerta, Belén; Borge, Carmen; Arenas, Antonio

2010-01-01

A cross-sectional study was carried out in natural wild rabbit (Oryctolagus cuniculus) populations from southern Spain to identify risk factors associated to myxoma virus infection. Blood samples from 619 wild rabbits were collected, and questionnaires which included variables related to host, disease, game management and environment were completed. A logistic regression analysis was conducted to investigate the associations between myxomatosis seropositivity (dependent variable) across 7 hunting estates and an extensive set of explanatory variables obtained from the questionnaires. The prevalence of antibodies against myxomatosis virus was 56.4% (95% CI: 52.5-60.3) and ranged between 21.4% (95% CI: 9.0-33.8) and 70.2% (95% CI: 58.3-82.1) among the different sampling areas. The logistic regression analysis showed that autumn (OR 9.0), high abundance of mosquitoes (OR 8.2), reproductive activity (OR 4.1), warren's insecticide treatment (OR 3.7), rabbit haemorrhagic disease (RHD) seropositivity (OR 2.6), high hunting pressure (OR 6.3) and sheep presence (OR 6.4) were associated with seropositivity to myxomatosis. Based on the results, diverse management measures for myxomatosis control are proposed.

Health plans' disease management programs: extending across the medical and behavioral health spectrum?

PubMed

Merrick, Elizabeth Levy; Horgan, Constance M; Garnick, Deborah W; Hodgkin, Dominic; Morley, Melissa

2008-01-01

Although the disease management industry has expanded rapidly, there is little nationally representative data regarding medical and behavioral health disease management programs at the health plan level. National estimates from a survey of private health plans indicate that 90% of health plan products offered disease management for general medical conditions such as diabetes but only 37% had depression programs. The frequency of specific depression disease management activities varied widely. Program adoption was significantly related to product type and behavioral health contracting. In health plans, disease management has penetrated more slowly into behavioral health and depression program characteristics are highly variable.

Health Plans' Disease Management Programs: Extending across the Medical and Behavioral Health Spectrum?

PubMed Central

Merrick, Elizabeth Levy; Horgan, Constance M.; Garnick, Deborah W.; Hodgkin, Dominic; Morley, Melissa

2015-01-01

While the disease management industry has expanded rapidly, there is little nationally representative data regarding medical and behavioral health disease management programs at the health plan level. National estimates from a survey of private health plans indicate that 90% of health plan products offered disease management for general medical conditions such as diabetes, but only 37% had depression programs. The frequency of specific depression disease management activities varied widely. Program adoption was significantly related to product type and behavioral health contracting. In health plans, disease management has penetrated more slowly into behavioral health, and depression program characteristics are highly variable. PMID:18806594

Occupational lung diseases.

PubMed

Furlow, Bryant

2011-01-01

Chest radiography and high-resolution computed tomography are indispensable tools in the detection, classification and characterization of occupational lung diseases that are caused by inhaling mineral particles such as asbestos, silicon-containing rock dust and other tissue-damaging antigens, nanomaterials and toxins. Radiographic evidence of occupational lung disease is interpreted with a patient's clinical signs and symptoms and a detailed occupational history in mind because of high variability in radiographic findings. This Directed Reading reviews the history, epidemiology, functional anatomy, pathobiology and medical diagnostic imaging of occupational lung diseases associated with inhalation of fine particulates in the workplace. This article is a Directed Reading. Your access to Directed Reading quizzes for continuing education credit is determined by your CE preference. For access to other quizzes, go to www.asrt.org/store.

Leptospirosis in American Samoa – Estimating and Mapping Risk Using Environmental Data

PubMed Central

Lau, Colleen L.; Clements, Archie C. A.; Skelly, Chris; Dobson, Annette J.; Smythe, Lee D.; Weinstein, Philip

2012-01-01

Background The recent emergence of leptospirosis has been linked to many environmental drivers of disease transmission. Accurate epidemiological data are lacking because of under-diagnosis, poor laboratory capacity, and inadequate surveillance. Predictive risk maps have been produced for many diseases to identify high-risk areas for infection and guide allocation of public health resources, and are particularly useful where disease surveillance is poor. To date, no predictive risk maps have been produced for leptospirosis. The objectives of this study were to estimate leptospirosis seroprevalence at geographic locations based on environmental factors, produce a predictive disease risk map for American Samoa, and assess the accuracy of the maps in predicting infection risk. Methodology and Principal Findings Data on seroprevalence and risk factors were obtained from a recent study of leptospirosis in American Samoa. Data on environmental variables were obtained from local sources, and included rainfall, altitude, vegetation, soil type, and location of backyard piggeries. Multivariable logistic regression was performed to investigate associations between seropositivity and risk factors. Using the multivariable models, seroprevalence at geographic locations was predicted based on environmental variables. Goodness of fit of models was measured using area under the curve of the receiver operating characteristic, and the percentage of cases correctly classified as seropositive. Environmental predictors of seroprevalence included living below median altitude of a village, in agricultural areas, on clay soil, and higher density of piggeries above the house. Models had acceptable goodness of fit, and correctly classified ∼84% of cases. Conclusions and Significance Environmental variables could be used to identify high-risk areas for leptospirosis. Environmental monitoring could potentially be a valuable strategy for leptospirosis control, and allow us to move from disease surveillance to environmental health hazard surveillance as a more cost-effective tool for directing public health interventions. PMID:22666516

Genetic susceptibility, colony size, and water temperature drive white-pox disease on the coral Acropora palmata.

PubMed

Muller, Erinn M; van Woesik, Robert

2014-01-01

Outbreaks of coral diseases are one of the greatest threats to reef corals in the Caribbean, yet the mechanisms that lead to coral diseases are still largely unknown. Here we examined the spatial-temporal dynamics of white-pox disease on Acropora palmata coral colonies of known genotypes. We took a Bayesian approach, using Integrated Nested Laplace Approximation algorithms, to examine which covariates influenced the presence of white-pox disease over seven years. We showed that colony size, genetic susceptibility of the coral host, and high-water temperatures were the primary tested variables that were positively associated with the presence of white-pox disease on A. palmata colonies. Our study also showed that neither distance from previously diseased individuals, nor colony location, influenced the dynamics of white-pox disease. These results suggest that white-pox disease was most likely a consequence of anomalously high water temperatures that selectively compromised the oldest colonies and the most susceptible coral genotypes.

Genetic Susceptibility, Colony Size, and Water Temperature Drive White-Pox Disease on the Coral Acropora palmata

PubMed Central

Muller, Erinn M.; van Woesik, Robert

2014-01-01

Outbreaks of coral diseases are one of the greatest threats to reef corals in the Caribbean, yet the mechanisms that lead to coral diseases are still largely unknown. Here we examined the spatial-temporal dynamics of white-pox disease on Acropora palmata coral colonies of known genotypes. We took a Bayesian approach, using Integrated Nested Laplace Approximation algorithms, to examine which covariates influenced the presence of white-pox disease over seven years. We showed that colony size, genetic susceptibility of the coral host, and high-water temperatures were the primary tested variables that were positively associated with the presence of white-pox disease on A. palmata colonies. Our study also showed that neither distance from previously diseased individuals, nor colony location, influenced the dynamics of white-pox disease. These results suggest that white-pox disease was most likely a consequence of anomalously high water temperatures that selectively compromised the oldest colonies and the most susceptible coral genotypes. PMID:25372835

The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

PubMed

Buchhorn, Reiner; Meint, Sebastian; Willaschek, Christian

2016-01-01

Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children-allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)-have the highest risk for 'stress diseases' such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children.

Context-specific parasitism in Tubifex tubifex in geothermally influenced stream reaches in Yellowstone National Park

USGS Publications Warehouse

Alexander, Julie D.; Kerans, Billie L.; Koel, Todd M.; Rasmussen, Charlotte

2011-01-01

Parasites can regulate host abundance and influence the composition and structure of communities. However, host-parasite interactions might be context-specific if environmental conditions can alter the outcome of parasitism and disease. An understanding of how host-parasite interactions might change in different contexts will be useful for predicting and managing disease against a background of anthropogenic environmental change. We examined the ecology of Myxobolus cerebralis, the parasite that causes whirling disease in salmonids, and its obligate host, Tubifex tubifex, in geothermally variable stream reaches in Yellowstone National Park. We identified reaches in 4 categories of geothermal influence, which were characterized by variable substrates, temperatures, specific conductivities, and pH. In each reach, we measured aspects of host ecology (abundance, relative abundance, size, and genotype of T. tubifex), parasite ecology (infection prevalence in T. tubifex and abundance of M. cerebralis-infected T. tubifex), and risk to fish of contracting whirling disease. Tubifex tubifex abundance was high all in reaches characterized by geothermal influence, whereas abundance of M. cerebralis-infected T. tubifex was high only in reaches characterized by intermediate geothermal influence. We suggest that habitat had a contextual effect on parasitism in the oligochaete host. Abundance of infected hosts appeared to depend on host abundance in all reach types except those with high geothermal influence, where abundance of infected hosts depended on environmental factors.

Intra-Individual Variability of Physical Activity in Older Adults With and Without Mild Alzheimer's Disease.

PubMed

Watts, Amber; Walters, Ryan W; Hoffman, Lesa; Templin, Jonathan

2016-01-01

Physical activity shows promise for protection against cognitive decline in older adults with and without Alzheimer's disease (AD). To better understand barriers to adoption of physical activity in this population, a clear understanding of daily and weekly activity patterns is needed. Most accelerometry studies report average physical activity over an entire wear period without considering the potential importance of the variability of physical activity. This study evaluated individual differences in the amount and intra-individual variability of physical activity and determined whether these differences could be predicted by AD status, day of wear, age, gender, education, and cardiorespiratory capacity. Physical activity was measured via accelerometry (Actigraph GT3X+) over one week in 86 older adults with and without AD (n = 33 and n = 53, respectively). Mixed-effects location-scale models were estimated to evaluate and predict individual differences in the amount and intra-individual variability of physical activity. Results indicated that compared to controls, participants with AD averaged 21% less activity, but averaged non-significantly greater intra-individual variability. Women and men averaged similar amounts of physical activity, but women were significantly less variable. The amount of physical activity differed significantly across days of wear. Increased cardiorespiratory capacity was associated with greater average amounts of physical activity. Investigation of individual differences in the amount and intra-individual variability of physical activity provided insight into differences by AD status, days of monitor wear, gender, and cardiovascular capacity. All individuals regardless of AD status were equally consistent in their physical activity, which may have been due to a highly sedentary sample and/or the early disease stage of those participants with AD. These results highlight the value of considering individual differences in both the amount and intra-individual variability of physical activity.

Factors Associated With Poor Glycemic Control or Wide Glycemic Variability Among Diabetes Patients in Hawaii, 2006–2009

PubMed Central

Sentell, Tetine; Tokumaru, Sheri; Goo, Roy; Davis, James W.; Mau, Marjorie M.

2012-01-01

Introduction Although glycemic control is known to reduce complications associated with diabetes, it is an elusive goal for many patients with diabetes. The objective of this study was to identify factors associated with sustained poor glycemic control, some glycemic variability, and wide glycemic variability among diabetes patients over 3 years. Methods This retrospective study was conducted among 2,970 diabetes patients with poor glycemic control (hemoglobin A1c [HbA1c] >9%) who were enrolled in a health plan in Hawaii in 2006. We conducted multivariable logistic regressions to examine factors related to sustained poor control, some glycemic variability, and wide glycemic variability during the next 3 years. Independent variables evaluated as possible predictors were age, sex, type of insurance coverage, morbidity, diabetes duration, history of cardiovascular disease, and number of medications. Results Longer duration of diabetes, being under age 35, and taking 15 or more medications were significantly associated with sustained poor glycemic control. Preferred provider organization and Medicare (vs health maintenance organization) enrollees and patients with high morbidity were less likely to have sustained poor glycemic control. Wide glycemic variability was significantly related to being younger than age 50, longer duration of diabetes, having coronary artery disease, and taking 5 to 9 medications per year. Conclusion Results indicate that duration of diabetes, age, number of medications, morbidity, and type of insurance coverage are risk factors for sustained poor glycemic control. Patients with these characteristics may need additional therapies and targeted interventions to improve glycemic control. Patients younger than age 50 and those with a history of coronary heart disease should be warned of the health risks of wide glycemic variability. PMID:23017247

Subjective Social Status and Cardiovascular Reactivity: An Experimental Examination

PubMed Central

Pieritz, Karoline; Süssenbach, Philipp; Rief, Winfried; Euteneuer, Frank

2016-01-01

The present experiment examined the causal influence of subjective social status (SSS) on variables related to cardiovascular health [i.e., blood pressure, heart rate variability (HRV)]. Participants were randomly assigned to one of two conditions involving a social comparison that either induced a temporary shift toward high SSS or toward low SSS. Cardiovascular variables were measured before (baseline), throughout, and after the manipulation (recovery). Participants in the low SSS condition had a significantly lower HRV during experimental manipulation than at baseline (p = 0.001). They also showed a significantly stronger HRV reactivity compared to participants in the high SSS condition (p = 0.027). Our results suggest that already temporary shifts of one's SSS have measureable effects on cardiovascular variables. They support the notion that social status plays a causal role in the development of cardiovascular disease. PMID:27486426

Partial central diabetes insipidus in patient with common variable immunodeficiency.

PubMed

Megías, Marta Cano; Matei, Ana Maria; Gonzalez Albarran, Olga; Perez Lopez, Gilberto

2012-07-03

Approximately 20% of patients with common variable immunodeficiency (CVID) have any autoimmune disease, as concurrent as prior to diagnosis, even during follow-up. In recent years, cases of CVID associated to endocrine autoimmune diseases have been reported. To our knowledge, no cases of CVID with diabetes insipidus has been reported previously. The authors present the case of a 37-year-old male, diagnosed of CVID, who had thirst, polyuria and nocturia for several years. After a water deprivation test and a complete resolution of patient's symptoms with vasopressin (DDAVP) treatment, diagnosis of partial central diabetes insipidus was finally made. Patients diagnosed of CVID could develop water misbalance due to posterior hypophysis autoimmune disorder. A high index of clinical suspicion, an early diagnosis and treatment of these disease could avoid future complications and improve the quality of life of these patients.

[The impact of psychological variables on the presentation and progress of asthma and patient's cognitive functions].

PubMed

Talarowska, Monika; Florkowski, Antoni; Gałecki, Piotr; Szemraj, Janusz; Zboralski, Krzysztof; Pietras, Tadeusz; Górski, Paweł

2009-01-01

Chronic respiratory system diseases become serious public health problem all over the world. The most prevalent are obstructive diseases (asthma and COPD). The prevalence of asthma is still high and concern patients representing wide range of age and socio-economic status. Despite progress in diagnostic and therapeutic options several studies showed that asthma has an impact on health-related quality of life and patients' coping. Asthma as chronic condition results in limitations of patients activity and social relations. Thus psychosocial variables, which may have an impact on asthma symptoms presentation and disease progress, should be considered. There are only few reports concerning cognitive functions in asthma. The aim of the study was to assess the potential impact of psychosocial factors on asthma symptoms presentation, and cognitive function in asthma patients.

Object-based assessment of burn severity in diseased forests using high-spatial and high-spectral resolution MASTER airborne imagery

NASA Astrophysics Data System (ADS)

Chen, Gang; Metz, Margaret R.; Rizzo, David M.; Dillon, Whalen W.; Meentemeyer, Ross K.

2015-04-01

Forest ecosystems are subject to a variety of disturbances with increasing intensities and frequencies, which may permanently change the trajectories of forest recovery and disrupt the ecosystem services provided by trees. Fire and invasive species, especially exotic disease-causing pathogens and insects, are examples of disturbances that together could pose major threats to forest health. This study examines the impacts of fire and exotic disease (sudden oak death) on forests, with an emphasis on the assessment of post-fire burn severity in a forest where trees have experienced three stages of disease progression pre-fire: early-stage (trees retaining dried foliage and fine twigs), middle-stage (trees losing fine crown fuels), and late-stage (trees falling down). The research was conducted by applying Geographic Object-Based Image Analysis (GEOBIA) to MASTER airborne images that were acquired immediately following the fire for rapid assessment and contained both high-spatial (4 m) and high-spectral (50 bands) resolutions. Although GEOBIA has gradually become a standard tool for analyzing high-spatial resolution imagery, high-spectral resolution data (dozens to hundreds of bands) can dramatically reduce computation efficiency in the process of segmentation and object-based variable extraction, leading to complicated variable selection for succeeding modeling. Hence, we also assessed two widely used band reduction algorithms, PCA (principal component analysis) and MNF (minimum noise fraction), for the delineation of image objects and the subsequent performance of burn severity models using either PCA or MNF derived variables. To increase computation efficiency, only the top 5 PCA and MNF and top 10 PCA and MNF components were evaluated, which accounted for 10% and 20% of the total number of the original 50 spectral bands, respectively. Results show that if no band reduction was applied the models developed for the three stages of disease progression had relatively similar performance, where both spectral responses and texture contributed to burn assessments. However, the application of PCA and MNF introduced much greater variation among models across the three stages. For the early-stage disease progression, neither band reduction algorithms improved or retained the accuracy of burn severity modeling (except for the use of 10 MNF components). Compared to the no-band-reduction scenario, band reduction led to a greater level of overestimation of low-degree burns and underestimation of medium-degree burns, suggesting that the spectral variation removed by PCA and MNF was vital for distinguishing between the spectral reflectance from disease-induced dried crowns (still retaining high structural complexity) and fire ash. For the middle-stage, both algorithms improved the model R2 values by 2-37%, while the late-stage models had comparable or better performance to those using the original 50 spectral bands. This could be explained by the loss of tree crowns enabling better signal penetration, thus leading to reduced spectral variation from canopies. Hence, spectral bands containing a high degree of random noise were correctly removed by the band reduction algorithms. Compared to the middle-stage, the late-stage forest stands were covered by large piles of fallen trees and branches, resulting in higher variability of MASTER imagery. The ability of band reduction to improve the model performance for these late-stage forest stands was reduced, because the valuable spectral variation representing the actual late-stage forest status was partially removed by both algorithms as noise. Our results indicate that PCA and MNF are promising for balancing computation efficiency and the performance of burn severity models in forest stands subject to the middle and late stages of sudden oak death disease progression. Compared to PCA, MNF dramatically reduced image spectral variation, generating larger image objects with less complexity of object shapes. Whereas, PCA-based models delivered superior performance in most evaluated cases suggesting that some key spectral variability contributing to the accuracy of burn severity models in diseased forests may have been removed together with true spectral noise through MNF transformations.

Automated gait and balance parameters diagnose and correlate with severity in Parkinson disease.

PubMed

Dewey, D Campbell; Miocinovic, Svjetlana; Bernstein, Ira; Khemani, Pravin; Dewey, Richard B; Querry, Ross; Chitnis, Shilpa; Dewey, Richard B

2014-10-15

To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD. Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests. 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses. Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2014-01-01

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

High-Risk Screening for Fabry Disease: Analysis by Tandem Mass Spectrometry of Globotriaosylceramide (Gb3 ) in Urine Collected on Filter Paper.

PubMed

Auray-Blais, Christiane; Lavoie, Pamela; Boutin, Michel; Abaoui, Mona

2017-04-06

Fabry disease is a complex, panethnic lysosomal storage disorder. It is characterized by the accumulation of glycosphingolipids in tissues, organs, the vascular endothelium, and biological fluids. The reported incidence in different populations is quite variable, ranging from 1:1400 to 1:117,000. Its complexity lies in the marked genotypic and phenotypic heterogeneity. Despite the fact that it is an X-linked disease, more than 600 mutations affect both males and females. In fact, some females may be affected as severely as males. The purpose of this protocol is to focus on the high-risk screening of patients who might have Fabry disease using a simple, rapid, non-invasive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for urinary globotriaosylceramide (Gb 3 ) analysis. Urine filter paper samples are easily collected at home by patients and sent by regular mail. This method has been successfully used for high-risk screening of patients with ophthalmologic manifestations and in an on-going study for high-risk screening of Fabry disease in patients with chronic kidney diseases. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Refining diagnosis of Parkinson's disease with deep learning-based interpretation of dopamine transporter imaging.

PubMed

Choi, Hongyoon; Ha, Seunggyun; Im, Hyung Jun; Paek, Sun Ha; Lee, Dong Soo

2017-01-01

Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies.

Distribution of Helicobacter pylori virulence markers in patients with gastroduodenal diseases in a region at high risk of gastric cancer.

PubMed

Wang, Ming-yi; Chen, Cheng; Gao, Xiao-zhong; Li, Jie; Yue, Jing; Ling, Feng; Wang, Xiao-chun; Shao, Shi-he

2013-01-01

Helicobacter pylori (H. pylori) is a major human pathogen that is responsible for various gastroduodenal diseases. We investigated the prevalence of H. pylori virulence markers in a region at high risk of gastric cancer. One hundred and sixteen H. pylori strains were isolated from patients with gastroduodenal diseases. cagA, the cagA 3' variable region, cagPAI genes, vacA, and dupA genotypes were determined by PCR, and some amplicons of the cagA 3' variable region, cagPAI genes and dupA were sequenced. cagA was detected in all strains. The cagA 3' variable region of 85 strains (73.3%) was amplified, and the sequences of 24 strains were obtained including 22 strains possessing the East Asian-type. The partial cagPAI presented at a higher frequency in chronic gastritis (44.4%) than that of the severe clinical outcomes (9.7%, p < 0.001). The most prevalent vacA genotypes were s1a/m2 (48.3%) and s1c/m2 (13.8%). Thirty-six strains (31.0%) possessed dupA and sequencing of dupA revealed an ORF of 2449-bp. The prevalence of dupA was significantly higher in strains from patients with the severe clinical outcomes (40.3%) than that from chronic gastritis (20.4%, p = 0.02). The high rate of East Asian-type cagA, intact cagPAI, virulent vacA genotypes, and the intact long-type dupA may underlie the high risk of gastric cancer in the region. Copyright © 2013 Elsevier Ltd. All rights reserved.

Why significant variables aren't automatically good predictors.

PubMed

Lo, Adeline; Chernoff, Herman; Zheng, Tian; Lo, Shaw-Hwa

2015-11-10

Thus far, genome-wide association studies (GWAS) have been disappointing in the inability of investigators to use the results of identified, statistically significant variants in complex diseases to make predictions useful for personalized medicine. Why are significant variables not leading to good prediction of outcomes? We point out that this problem is prevalent in simple as well as complex data, in the sciences as well as the social sciences. We offer a brief explanation and some statistical insights on why higher significance cannot automatically imply stronger predictivity and illustrate through simulations and a real breast cancer example. We also demonstrate that highly predictive variables do not necessarily appear as highly significant, thus evading the researcher using significance-based methods. We point out that what makes variables good for prediction versus significance depends on different properties of the underlying distributions. If prediction is the goal, we must lay aside significance as the only selection standard. We suggest that progress in prediction requires efforts toward a new research agenda of searching for a novel criterion to retrieve highly predictive variables rather than highly significant variables. We offer an alternative approach that was not designed for significance, the partition retention method, which was very effective predicting on a long-studied breast cancer data set, by reducing the classification error rate from 30% to 8%.

Highly dynamic animal contact network and implications on disease transmission

PubMed Central

Chen, Shi; White, Brad J.; Sanderson, Michael W.; Amrine, David E.; Ilany, Amiyaal; Lanzas, Cristina

2014-01-01

Contact patterns among hosts are considered as one of the most critical factors contributing to unequal pathogen transmission. Consequently, networks have been widely applied in infectious disease modeling. However most studies assume static network structure due to lack of accurate observation and appropriate analytic tools. In this study we used high temporal and spatial resolution animal position data to construct a high-resolution contact network relevant to infectious disease transmission. The animal contact network aggregated at hourly level was highly variable and dynamic within and between days, for both network structure (network degree distribution) and individual rank of degree distribution in the network (degree order). We integrated network degree distribution and degree order heterogeneities with a commonly used contact-based, directly transmitted disease model to quantify the effect of these two sources of heterogeneity on the infectious disease dynamics. Four conditions were simulated based on the combination of these two heterogeneities. Simulation results indicated that disease dynamics and individual contribution to new infections varied substantially among these four conditions under both parameter settings. Changes in the contact network had a greater effect on disease dynamics for pathogens with smaller basic reproduction number (i.e. R0 < 2). PMID:24667241

Risk stratification using stress echocardiography: incremental prognostic value over historic, clinical, and stress electrocardiographic variables across a wide spectrum of bayesian pretest probabilities for coronary artery disease.

PubMed

Bangalore, Sripal; Gopinath, Devi; Yao, Siu-Sun; Chaudhry, Farooq A

2007-03-01

We sought to evaluate the risk stratification ability and incremental prognostic value of stress echocardiography over historic, clinical, and stress electrocardiographic (ECG) variables, over a wide spectrum of bayesian pretest probabilities of coronary artery disease (CAD). Stress echocardiography is an established technique for the diagnosis of CAD. However, data on incremental prognostic value of stress echocardiography over historic, clinical, and stress ECG variables in patients with known or suggested CAD is limited. We evaluated 3259 patients (60 +/- 13 years, 48% men) undergoing stress echocardiography. Patients were grouped into low (<15%), intermediate (15-85%), and high (>85%) pretest CAD likelihood subgroups using standard software. The historical, clinical, stress ECG, and stress echocardiographic variables were recorded for the entire cohort. Follow-up (2.7 +/- 1.1 years) for confirmed myocardial infarction (n = 66) and cardiac death (n = 105) was obtained. For the entire cohort, an ischemic stress echocardiography study confers a 5.0 times higher cardiac event rate than the normal stress echocardiography group (4.0% vs 0.8%/y, P < .0001). Furthermore, Cox proportional hazard regression model showed incremental prognostic value of stress echocardiography variables over historic, clinical, and stress ECG variables across all pretest probability subgroups (global chi2 increased from 5.1 to 8.5 to 20.1 in the low pretest group, P = .44 and P = .01; from 20.9 to 28.2 to 116 in the intermediate pretest group, P = .47 and P < .0001; and from 17.5 to 36.6 to 61.4 in the high pretest group, P < .0001 for both groups). A normal stress echocardiography portends a benign prognosis (<1% event rate/y) in all pretest probability subgroups and even in patients with high pretest probability and yields incremental prognostic value over historic, clinical, and stress ECG variables across all pretest probability subgroups. The best incremental value is, however, in the intermediate pretest probability subgroup.

Mind over matter: cognitive - behavioral determinants of emotional distress in multiple sclerosis patients.

PubMed

Chalk, Holly McCartney

2007-10-01

Given the high incidence and unique symptomatology of depression in multiple sclerosis (MS) patients, the current study examined the role of cognitive and behavioral variables in predicting psychosocial adjustment in this population, in order to suggest psychotherapeutic interventions tailored specifically to MS patients. Data from 329 MS patients indicated that problem solving coping, acceptance coping, and challenge appraisals were associated with positive psychological adjustment (i.e., high life satisfaction, low depression and anxiety), whereas variables measuring disease severity (i.e., illness duration, subjective health status, and self-reported disability) were not associated with adjustment. These findings suggest that MS patients' psychological outcomes are more related to controllable cognitive and behavioral factors than to the physical effects of the disease. Consequently, it is expected that interventions that target these specific coping strategies and cognitive appraisals will be effective in treating the emotional effects of MS.

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

PubMed Central

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

2015-01-01

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

Localized scleroderma: clinical spectrum and therapeutic update*

PubMed Central

Careta, Mariana Figueiroa; Romiti, Ricardo

2015-01-01

Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma. PMID:25672301

Localized scleroderma: clinical spectrum and therapeutic update.

PubMed

Careta, Mariana Figueiroa; Romiti, Ricardo

2015-01-01

Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma.

Predictive variables for the occurrence of early clinical mastitis in primiparous Holstein cows under field conditions in France.

PubMed Central

Barnouin, J; Chassagne, M

2001-01-01

Holstein heifers from 47 dairy herds in France were enrolled in a field study to determine predictors for clinical mastitis within the first month of lactation. Precalving and calving variables (biochemical, hematological, hygienic, and disease indicators) were collected. Early clinical mastitis (ECM) predictive variables were analyzed by using a multiple logistic regression model (99 cows with ECM vs. 571 without clinical mastitis throughout the first lactation). Two variables were associated with a higher risk of ECM: a) difficult calving and b) medium and high white blood cell (WBC) counts in late gestation. Two prepartum indicators were associated with a lower ECM risk: a) medium and high serum concentrations of immunoglobulin G1 (IgG1) and b) high percentage of eosinophils among white blood cells. Calving difficulty and certain biological blood parameters (IgG1, eosinophils) could represent predictors that would merit further experimental studies, with the aim of designing programs for reducing the risk of clinical mastitis in the first lactation. PMID:11195522

Landscape epidemiology and machine learning: A geospatial approach to modeling West Nile virus risk in the United States

NASA Astrophysics Data System (ADS)

Young, Sean Gregory

The complex interactions between human health and the physical landscape and environment have been recognized, if not fully understood, since the ancient Greeks. Landscape epidemiology, sometimes called spatial epidemiology, is a sub-discipline of medical geography that uses environmental conditions as explanatory variables in the study of disease or other health phenomena. This theory suggests that pathogenic organisms (whether germs or larger vector and host species) are subject to environmental conditions that can be observed on the landscape, and by identifying where such organisms are likely to exist, areas at greatest risk of the disease can be derived. Machine learning is a sub-discipline of artificial intelligence that can be used to create predictive models from large and complex datasets. West Nile virus (WNV) is a relatively new infectious disease in the United States, and has a fairly well-understood transmission cycle that is believed to be highly dependent on environmental conditions. This study takes a geospatial approach to the study of WNV risk, using both landscape epidemiology and machine learning techniques. A combination of remotely sensed and in situ variables are used to predict WNV incidence with a correlation coefficient as high as 0.86. A novel method of mitigating the small numbers problem is also tested and ultimately discarded. Finally a consistent spatial pattern of model errors is identified, indicating the chosen variables are capable of predicting WNV disease risk across most of the United States, but are inadequate in the northern Great Plains region of the US.

Relationship between cardiac autonomic function and cognitive function in Alzheimer's disease.

PubMed

Nonogaki, Zen; Umegaki, Hiroyuki; Makino, Taeko; Suzuki, Yusuke; Kuzuya, Masafumi

2017-01-01

Alzheimer's disease (AD) affects many central nervous structures and neurotransmitter systems. These changes affect not only cognitive function, but also cardiac autonomic function. However, the functional relationship between cardiac autonomic function and cognition in AD has not yet been investigated. The objective of the present study was to evaluate the association between cardiac autonomic function measured by heart rate variability and cognitive function in AD. A total of 78 AD patients were recruited for this study. Cardiac autonomic function was evaluated using heart rate variability analysis. Multiple linear regression analysis was used to model the association between heart rate variability and cognitive function (global cognitive function, memory, executive function and processing speed), after adjustment for covariates. Global cognitive function was negatively associated with sympathetic modulation (low-to-high frequency power ratio). Memory performance was positively associated with parasympathetic modulation (high frequency power) and negatively associated with sympathetic modulation (low-to-high frequency power ratio). These associations were independent of age, sex, educational years, diabetes, hypertension and cholinesterase inhibitor use. Cognitive function, especially in the areas of memory, is associated with cardiac autonomic function in AD. Specifically, lower cognitive performance was found to be associated with significantly higher cardiac sympathetic and lower parasympathetic function in AD. Geriatr Gerontol Int 2017; 17: 92-98. © 2015 Japan Geriatrics Society.

Health, lifestyle, belief and knowledge differences between two ethnic groups with specific reference to tobacco, diet and physical activity.

PubMed

Anthony, Denis; Baggott, Rob; Tanner, Judith; Jones, Kathryn; Evans, Hala; Perkins, Gill; Palmer, Hilary

2012-11-01

  To compare physical activity levels, body mass index, habitual diet, tobacco use and prevalence of non-communicable disease between the two ethnic groups and to identify predictors for differences between groups.   Tobacco use, poor diet and physical inactivity are major lifestyle risk factors for chronic cardiovascular diseases, certain cancers, diabetes and chronic lung diseases. There are higher risk and incidence of these diseases in some ethnic groups, for example Asians have higher incidence of diabetes.   Cross sectional survey.   Cross sectional survey of Asians of Indian descent and white British adults conducted between October-December 2009. Main outcome variables were lifestyle behaviours and BMI. Self-reported disease diagnosis was also collected. In a regression analysis, predictors of outcome variables were demographic variables and beliefs/attitudes/knowledge towards lifestyle behaviours.   Body mass index, tobacco use and non-communicable disease (except diabetes) were lower in Indians. Indians reported lower physical activity levels and greater salt use than Whites. Tobacco use was higher in Whites, but knowledge, attitudes and beliefs were similar between Whites and Indians.   Health risk behaviour and morbidity are different between the two ethnic groups. Gender, age, educational level, beliefs, attitudes and knowledge do not explain these differences. Health promotion that aims to improve knowledge will probably not work and innovative methods are needed to improve health in high risk groups. © 2012 Blackwell Publishing Ltd.

Baseline coral disease surveys within three marine parks in Sabah, Borneo.

PubMed

Miller, Jennifer; Sweet, Michael J; Wood, Elizabeth; Bythell, John

2015-01-01

Two of the most significant threats to coral reefs worldwide are bleaching and disease. However, there has been a scarcity of research on coral disease in South-East Asia, despite the high biodiversity and the strong dependence of local communities on the reefs in the region. This study provides baseline data on coral disease frequencies within three national parks in Sabah, Borneo, which exhibit different levels of human impacts and management histories. High mean coral cover (55%) and variable disease frequency (mean 0.25 diseased colonies m(-2)) were found across the three sites. Highest disease frequency (0.44 diseased colonies per m(2)) was seen at the site closest to coastal population centres. Bleaching and pigmentation responses were actually higher at Sipadan, the more remote, offshore site, whereas none of the other coral diseases detected in the other two parks were detected in Sipadan. Results of this study offer a baseline dataset of disease in these parks and indicate the need for continued monitoring, and suggest that coral colonies in parks under higher anthropogenic stressors and with lower coral cover may be more susceptible to contracting disease.

Development and validation of a risk calculator predicting exercise-induced ventricular arrhythmia in patients with cardiovascular disease.

PubMed

Hermes, Ilarraza-Lomelí; Marianna, García-Saldivia; Jessica, Rojano-Castillo; Carlos, Barrera-Ramírez; Rafael, Chávez-Domínguez; María Dolores, Rius-Suárez; Pedro, Iturralde

2016-10-01

Mortality due to cardiovascular disease is often associated with ventricular arrhythmias. Nowadays, patients with cardiovascular disease are more encouraged to take part in physical training programs. Nevertheless, high-intensity exercise is associated to a higher risk for sudden death, even in apparently healthy people. During an exercise testing (ET), health care professionals provide patients, in a controlled scenario, an intense physiological stimulus that could precipitate cardiac arrhythmia in high risk individuals. There is still no clinical or statistical tool to predict this incidence. The aim of this study was to develop a statistical model to predict the incidence of exercise-induced potentially life-threatening ventricular arrhythmia (PLVA) during high intensity exercise. 6415 patients underwent a symptom-limited ET with a Balke ramp protocol. A multivariate logistic regression model where the primary outcome was PLVA was performed. Incidence of PLVA was 548 cases (8.5%). After a bivariate model, thirty one clinical or ergometric variables were statistically associated with PLVA and were included in the regression model. In the multivariate model, 13 of these variables were found to be statistically significant. A regression model (G) with a X(2) of 283.987 and a p<0.001, was constructed. Significant variables included: heart failure, antiarrhythmic drugs, myocardial lower-VD, age and use of digoxin, nitrates, among others. This study allows clinicians to identify patients at risk of ventricular tachycardia or couplets during exercise, and to take preventive measures or appropriate supervision. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature.

PubMed

Dell'Isola, A; Allan, R; Smith, S L; Marreiros, S S P; Steultjens, M

2016-10-12

Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease. The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies. A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time. This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population.

[Effectiveness of virtual immersion programmes in patients with Parkinson's disease. A systematic review].

PubMed

Morales-Gomez, S; Elizagaray-Garcia, I; Yepes-Rojas, O; de la Puente-Ranea, L; Gil-Martinez, A

2018-02-01

Parkinson disease (PD) is the second most common neurodegenerative disease. Virtual reality (VR) is being used in rehabilitation of neurological patients. To analyze the VR systems' therapeutically effectiveness through PD diagnosed subjects with variables of motor, quality of life and cognition. Electronics database were used to look for articles: Medline, EMBASE, PEDro, CINAHL and Cochrane. The inclusion criteria were: randomized control trial (RCT) performed in PD with at least one VR variable included in the therapeutically treatment and diagnosed PD subjects. Four RCT were chosen showing all good methodology quality. Concordance between evaluators was moderate-high. VR was the main treatment in all of them. VR was more effective in balance improvement in PD subjects than conventional physiotherapy in two RCT. VR was not more effective in balance improvement in PD subjects than conventional physiotherapy in two RCT. Contradictory evidences where showed between the effectiveness of the VR programs versus conventional programs in the effectiveness of balance treatment with PD subjects. Non-motor variables improvement was not greater in subjects with VR treatments versus the ones with conventional physiotherapy in the four RCT. The treatments with VR cannot be assumed as more effectives than conventional physiotherapy through PD subjects in motor and psychosocial variables.

Phenotype/genotype correlations in Gaucher disease type 1: Clinical and therapeutic implications

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

Sibille, A.; Eng, C.M.; Kim, S.J.

1993-06-01

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among Ashkenazi Jews. Gaucher disease type 1 is characterized by marked variability of the phenotype and by the absence of neuronopathic involvement. To test the hypothesis that this phenotypic variability was due to genetic compounds of several different mutant alleles, 161 symptomatic patients with Gaucher disease type 1 (> 90% Ashkenazi Jewish) were analyzed for clinical involvement, and their genotypes were determined. Qualitative and quantitative measures of disease involvement included age at onset of the disease manifestations, hepatic and splenic volumes, age at splenectomy, andmore » severity of bony disease. High statistically significant differences (P < .005) were found in each clinical parameter in patients with the N370S/N370S genotype compared with those patients with the N370S/84GG, N370S/L444P, and N370/ genotypes. The symptomatic N370S homozygotes had onset of their disease two to three decades later than patients with the other genotypes. In addition, patients with the latter genotypes have much more severely involved livers, spleens, and bones and had a higher incidence of splenectomy at an earlier age. These predictive genotype analyses provide the basis for genetic care delivery and therapeutic recommendations in patients affected with Gaucher disease type 1. 38 refs., 1 fig., 4 tabs.« less

Association of hematologic variables and castration status at the time of arrival at a research facility with the risk of bovine respiratory disease in beef calves.

PubMed

Richeson, John T; Pinedo, Pablo J; Kegley, Elizabeth B; Powell, Jeremy G; Gadberry, M Shane; Beck, Paul A; Falkenberg, Shollie M

2013-10-01

To determine the association of CBC variables and castration status at the time of arrival at a research facility with the risk of development of bovine respiratory disease (BRD). Retrospective cohort study. 1,179 crossbred beef bull (n = 588) and steer (591) calves included in 4 experiments at 2 University of Arkansas research facilities. Calves underwent processing and treatments in accordance with the experiment in which they were enrolled. Castration status and values of CBC variables were determined at the time of arrival at the facilities. Calves were monitored to detect signs of BRD during a 42-day period. The areas under the receiving operator characteristic curves for CBC variables with significant contrast test results ranged from 0.51 (neutrophil count) to 0.67 (eosinophil count), indicating they were limited predictors of BRD in calves. The only CBC variables that had significant associations with BRD in calves as determined via multivariable logistic regression analysis were eosinophil and RBC counts. The odds of BRD for bulls were 3.32 times the odds of BRD for steers. Results of this study indicated that low eosinophil and high RBC counts in blood samples may be useful for identification of calves with a high risk for development of BRD. Further research may be warranted to validate these variables for prediction of BRD in calves. Calves that were bulls at the time of arrival had a higher risk of BRD, versus calves that were steers at that time.

Elevated Blood Neutrophil-to-Lymphocyte Ratio: A Readily Available Biomarker Associated with Death due to Disease in High Risk Nonmetastatic Melanoma.

PubMed

Davis, Jeremy L; Langan, Russell C; Panageas, Katherine S; Zheng, Junting; Postow, Michael A; Brady, Mary S; Ariyan, Charlotte; Coit, Daniel G

2017-07-01

Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, nonmetastatic melanoma. Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within 2 weeks before operation. Multiple primary melanomas and concurrent hematologic or other metastatic malignancies were excluded. Cumulative incidence of death due to disease was estimated, and Gray's test was used to examine the effect of NLR on melanoma disease-specific death (DOD). Multivariable competing risks regression models assessed associated factors. Data on 1431 patients with high-risk, nonmetastatic melanoma were analyzed. Median follow-up for survivors was 4 years. High NLR (≥3 or as continuous variable) was associated with older age, male sex, thicker primaries, higher mitotic index, and more advanced nodal status. On multivariate analysis, high NLR (≥3 or as a continuous variable), older age, male sex, ulcerated primary, lymphovascular invasion, and positive nodal status were all independently associated with worse DOD. NLR is a readily available blood test that was independently associated with DOD in patients with high-risk, nonmetastatic melanoma. It is unclear whether high NLR is a passive indicator of poor prognosis or a potential therapeutic target. Further studies to evaluate the prognostic role of NLR to potentially identify those more likely to benefit from adjuvant immunotherapy may prove informative.

Cost of management in epistaxis admission: Impact of patient and hospital characteristics.

PubMed

Goljo, Erden; Dang, Rajan; Iloreta, Alfred M; Govindaraj, Satish

2015-12-01

To investigate patient and hospital characteristics associated with increased cost and length of stay in the inpatient management of epistaxis. Retrospective cross-sectional study of the 2008 to 2012 National (Nationwide) Inpatient Sample. Patient and hospital characteristics of epistaxis admissions were analyzed. Multiple linear regression analysis was used to ascertain variables associated with increased cost and length of hospital stay. Variables significantly associated with high cost were further analyzed to determine the contribution of operative intervention and total procedures to cost. A total of 16,828 patients with an admitting diagnosis of epistaxis were identified. The average age was 67.5; 52.3% of the patients were male; 73.3% of the patients were Caucasian; and 70.7% of the hospital stays were government funded. The average length of stay was 3.24 days, and average hospitalization cost was $6,925. Longer length of stay was associated with black race, alcohol abuse, sinonasal disease, renal disease, Medicaid, and care at a northeastern U.S. hospital. Increased hospitalization costs of > $1,000 were associated with Asian/Pacific Islander race; sinonasal disease; renal disease; top income quartile; and care at urban teaching, northeastern, and western hospitals in the United States. High costs were predicted by procedural intervention in patients with comorbid alcohol abuse, sinonasal disease, renal disease, patients with private insurance, and patients managed at large hospitals. Although hospitalization costs are complex and multifactorial, we were able to identify patient and hospital characteristics associated with high costs in the management of epistaxis. Early identification and intervention, combined with implementation of targeted hospital management protocols, may improve outcomes and reduce financial burden. 2C. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

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

PubMed Central

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

2009-01-01

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

Evidence-based veterinary dentistry: a systematic review of homecare for prevention of periodontal disease in dogs and cats.

PubMed

Roudebush, Philip; Logan, Ellen; Hale, Fraser A

2005-03-01

Successful treatment and prevention of periodontal disease in pet animals requires a multidimensional approach to identify and eliminate exacerbating factors, provide scheduled professional examinations and care, and plan and implement a dental homecare program. Over the years, many therapeutic and preventive interventions have been developed or advocated for periodontal disease, but evidence of efficacy or effectiveness is highly variable. Accordingly, the main objective of this systematic review is to identify and critically appraise the evidence supporting various aspects of homecare for prevention of canine and feline periodontal disease.

Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10.

PubMed

Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

2014-09-01

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.

Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10

PubMed Central

Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

2014-01-01

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. PMID:24845202

Variability in Deposition Rates and Mean Days of Hospitalization for the 100 Most Common Diagnostic Codes in U.S. Army Health Services Command Facilities.

DTIC Science & Technology

1992-06-02

artificially high degree of variability across regions. Mean bed days reflect provider behavior once the patient is hospitalized. However, variation in...0.12 3 4149 CHRONIC ISCHEMIC HEARR DISEASE :3.55 4.01 7.47 1.15 ’ 5243 ANOMALIES TOOTH POSITION 1.25 0.94 11.69 0.46 9 6565 POOR FETAL GROWTH 9.26

Inferior outcomes for black children with high risk acute lymphoblastic leukemia and the impact of socioeconomic variables.

PubMed

Walsh, Alexandra; Chewning, Joseph; Li, Xuelin; Dai, Chen; Whelan, Kimberly; Madan-Swain, Avi; Waterbor, John; Baskin, Monica L; Goldman, Frederick D

2017-02-01

While significant improvements have been made for children with acute lymphoblastic leukemia (ALL) in the United States over the past 20 years, black patients continue to have inferior outcomes. The full impact of socioeconomic variables on outcomes in this minority population is not entirely understood. Disease characteristics, demographic, and socioeconomic status (SES) variables were collected on black (n = 44) and white (n = 178) patients diagnosed at the University of Alabama at Birmingham. Cox proportional hazard regression was used to evaluate the influence of SES and insurance status on survival. As a cohort, 5-year overall survival (OS) was 87% (82-91%), with a median follow-up of 99 months. In univariable analysis, black race was not significantly associated with a higher risk of death or relapse and death. White and black patients with standard-risk leukemia had excellent outcomes, with 97% (91-99%) and 96% (75-99%) 5-year OS, respectively. In contrast, for high-risk disease, white patients had a statistically significant improved 5-year OS rates compared with black patients (79% [68-87%] vs. 52% [28-72%]). Black children were more likely to have public insurance, and, in multivariable analysis, this was associated with a trend toward an improved outcome. Black patients also had poorer census tract-level SES parameters, but these variables were not associated with survival. Our study demonstrates significantly inferior outcomes for black children with high-risk leukemia. These outcome disparities were not related to SES variables, including poverty or private insurance coverage, suggesting the involvement of other factors and highlighting the need for a prospective investigative analysis. © 2016 Wiley Periodicals, Inc.

Clustering high-dimensional mixed data to uncover sub-phenotypes: joint analysis of phenotypic and genotypic data.

PubMed

McParland, D; Phillips, C M; Brennan, L; Roche, H M; Gormley, I C

2017-12-10

The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, 7 years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the 7-year follow-up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

A map of human microRNA variation uncovers unexpectedly high levels of variability

PubMed Central

2012-01-01

Background MicroRNAs (miRNAs) are key components of the gene regulatory network in many species. During the past few years, these regulatory elements have been shown to be involved in an increasing number and range of diseases. Consequently, the compilation of a comprehensive map of natural variability in a healthy population seems an obvious requirement for future research on miRNA-related pathologies. Methods Data on 14 populations from the 1000 Genomes Project were analyzed, along with new data extracted from 60 exomes of healthy individuals from a population from southern Spain, sequenced in the context of the Medical Genome Project, to derive an accurate map of miRNA variability. Results Despite the common belief that miRNAs are highly conserved elements, analysis of the sequences of the 1,152 individuals indicated that the observed level of variability is double what was expected. A total of 527 variants were found. Among these, 45 variants affected the recognition region of the corresponding miRNA and were found in 43 different miRNAs, 26 of which are known to be involved in 57 diseases. Different parts of the mature structure of the miRNA were affected to different degrees by variants, which suggests the existence of a selective pressure related to the relative functional impact of the change. Moreover, 41 variants showed a significant deviation from the Hardy-Weinberg equilibrium, which supports the existence of a selective process against some alleles. The average number of variants per individual in miRNAs was 28. Conclusions Despite an expectation that miRNAs would be highly conserved genomic elements, our study reports a level of variability comparable to that observed for coding genes. PMID:22906193

Risk Zone Modelling and Early Warning System for Visceral Leishmaniasis Kala-Azar Disease in Bihar, India Using Remote Sensing and GIS

NASA Astrophysics Data System (ADS)

Jeyaram, A.; Kesari, S.; Bajpai, A.; Bhunia, G. S.; Krishna Murthy, Y. V. N.

2012-07-01

Visceral Leishmaniasis (VL) commonly known as Kala-azar is one of the most neglected tropical disease affecting approximately 200 million poorest populations 'at risk in 109 districts of three endemic countries namely Bangladesh, India and Nepal at different levels. This tropical disease is caused by the protozoan parasite Leishmania donovani and transmitted by female Phlebotomus argentipes sand flies. The analysis of disease dynamics indicate the periodicity at seasonal and inter-annual temporal scale which forms the basis for development of advanced early warning system. Study area of highly endemic Vaishali district, Bihar, India has been taken for model development. A Systematic study of geo-environmental parameters derived from satellite data in conjunction with ground intelligence enabled modelling of infectious disease and risk villages. High resolution Indian satellites data of IRS LISS IV (multi-spectral) and Cartosat-1 (Pan) have been used for studying environmentally risk parameters viz. peri-domestic vegetation, dwelling condition, wetland ecosystem, cropping pattern, Normalised Difference Vegetation Index (NDVI), detailed land use etc towards risk assessment. Univariate analysis of the relationship between vector density and various land cover categories and climatic variables suggested that all the variables are significantly correlated. Using the significantly correlated variables with vector density, a seasonal multivariate regression model has been carried out incorporating geo-environmental parameters, climate variables and seasonal time series disease parameters. Linear and non-linear models have been applied for periodicity and interannual temporal scale to predict Man-hour-density (MHD) and 'out-of-fit' data set used for validating the model with reasonable accuracy. To improve the MHD predictive approach, fuzzy model has also been incorporated in GIS environment combining spatial geo-environmental and climatic variables using fuzzy membership logic. Based on the perceived importance of the geoenvironmental parameters assigned by epidemiology expert, combined fuzzy membership has been calculated. The combined fuzzy membership indicate the predictive measure of vector density in each village. A γ factor has been introduced to have increasing effect in the higher side and decreasing effect in the lower side which facilitated for prioritisation of the villages. This approach is not only to predict vector density but also to prioritise the villages for effective control measures. A software package for modelling the risk villages integrating multivariate regression and fuzzy membership analysis models have been developed to estimate MHD (vector density) as part of the early warning system.

The partial volume effect in the quantification of 1H magnetic resonance spectroscopy in Alzheimer's disease and aging.

PubMed

Mato Abad, Virginia; Quirós, Alicia; García-Álvarez, Roberto; Loureiro, Javier Pereira; Alvarez-Linera, Juan; Frank, Ana; Hernández-Tamames, Juan Antonio

2014-01-01

1H-MRS variability increases due to normal aging and also as a result of atrophy in grey and white matter caused by neurodegeneration. In this work, an automatic process was developed to integrate data from spectra and high-resolution anatomical images to quantify metabolites, taking into account tissue partial volumes within the voxel of interest avoiding additional spectra acquisitions required for partial volume correction. To evaluate this method, we use a cohort of 135 subjects (47 male and 88 female, aged between 57 and 99 years) classified into 4 groups: 38 healthy participants, 20 amnesic mild cognitive impairment patients, 22 multi-domain mild cognitive impairment patients, and 55 Alzheimer's disease patients. Our findings suggest that knowing the voxel composition of white and grey matter and cerebrospinal fluid is necessary to avoid partial volume variations in a single-voxel study and to decrease part of the variability found in metabolites quantification, particularly in those studies involving elder patients and neurodegenerative diseases. The proposed method facilitates the use of 1H-MRS techniques in statistical studies in Alzheimer's disease, because it provides more accurate quantitative measurements, reduces the inter-subject variability, and improves statistical results when performing group comparisons.

Efficacy of canine influenza virus (H3N8) vaccine to decrease severity of clinical disease after co-challenge with canine influenza virus and Streptococcus equi subsp. Zooepidemicus

USDA-ARS?s Scientific Manuscript database

Since first emerging into the North American canine population in 2004, canine influenza virus (CIV) subtype H3N8 has shown horizontal transmission among dogs, with a high level of adaptation to this species. Severity of disease is variable, and co-infection by other respiratory pathogens is an impo...

Chronic disease prevalence and associations in a cohort of Australian men: The Florey Adelaide Male Ageing Study (FAMAS)

PubMed Central

Martin, Sean A; Haren, Matthew T; Taylor, Anne W; Middleton, Sue M; Wittert, Gary A

2008-01-01

Background An increasing proportion of Australia's chronic disease burden is carried by the ageing male. The aim of this study was to determine the prevalence of asthma, cancer, diabetes, angina and musculoskeletal conditions and their relationship to behavioural and socio-demographic factors in a cohort of Australian men. Methods Self-reports of disease status were obtained from baseline clinic visits (August 2002 – July 2003 & July 2004 – May 2005) from 1195 randomly selected men, aged 35–80 years and living in the north-west regions of Adelaide. Initially, relative risks were assessed by regression against selected variables for each outcome. Where age-independent associations were observed with the relevant chronic disease, independent variables were fitted to customized multiadjusted models. Results The prevalence of all conditions was moderately higher in comparison to national data for age-matched men. In particular, there was an unusually high rate of men with cancer. Multiadjusted analyses revealed age as a predictor of chronic conditions (type 2 diabetes mellitus, angina, cancer & osteoarthritis). A number of socio-demographic factors, independent of age, were associated with chronic disease, including: low income status (diabetes), separation/divorce (asthma), unemployment (cancer), high waist circumference (diabetes), elevated cholesterol (angina) and a family history of obesity (angina). Conclusion Socio-demographic factors interact to determine disease status in this broadly representative group of Australian men. In addition to obesity and a positive personal and family history of disease, men who are socially disadvantaged (low income, unemployed, separated) should be specifically targeted by public health initiatives. PMID:18664294

Medication adherence among patients in a chronic disease clinic.

PubMed

Tourkmani, Ayla M; Al Khashan, Hisham I; Albabtain, Monirah A; Al Harbi, Turki J; Al Qahatani, Hala B; Bakhiet, Ahmed H

2012-12-01

To assess motivation and knowledge domains of medication adherence intention, and to determine their predictors in an ambulatory setting. We conducted a cross-sectional survey study among patients attending a chronic disease clinic at the Family and Community Medicine Department, Prince Sultan Military Medical City, Riyadh, Kingdom of Saudi Arabia between June and September 2010. Adherence intention was assessed using Modified Morisky Scale. Predictors of low motivation and/or knowledge were determined using logistic regression models. A total of 347 patients were interviewed during the study duration. Most patients (75.5%) had 2 or more chronic diseases with an average of 6.3 +/- 2.3 medications, and 6.5 +/- 2.9 pills per prescription. The frequency of adherence intention was low (4.6%), variable (37.2%), and high (58.2%). In multivariate logistic regression analysis, younger age and having asthma were significantly associated with low motivation, while male gender, single status, and not having hypertension were significantly associated with low knowledge. Single status was the only independent predictor of low adherence intention. In a population with multiple chronic diseases and high illiteracy rate, more than 40% had low/variable intention to adhere to prescribed medications. Identifying predictors of this group may help in providing group-specific interventional programs.

Association between periodontal disease and dementia: A literature review.

PubMed

Pazos, P; Leira, Y; Domínguez, C; Pías-Peleteiro, J M; Blanco, J; Aldrey, J M

2016-10-22

Periodontal disease and dementia are very prevalent, especially in elderly populations. Multiple studies have shown a link between these diseases; however, the conditions are highly heterogeneous and so is the diagnostic methodology, which may hinder interpretation and comparison of the results. The aim of this article is to provide a critical review of the literature linking these 2 processes. We retrieved 22 studies, most of which were retrospective, and analysed various methodological variables including study population, diagnosis of periodontitis, definition of dementia, adjusted variables, and results. The different aetiopathogenic mechanisms that may affect the progression and interaction of these 2 conditions were also analysed. Although available evidence indicates a positive association between periodontitis and dementia, both the strength of that association and the presence of a causal relationship have yet to be determined. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Pediatric common variable immunodeficiency: immunologic and phenotypic associations with switched memory B cells.

PubMed

Yong, Pierre L; Orange, Jordan S; Sullivan, Kathleen E

2010-08-01

Recent studies suggest that patients with common variable immunodeficiency (CVID) and low numbers of switched memory B cells have lower IgG levels and higher rates of autoimmune disease, splenomegaly, and granulomatous disease; however, no prior literature has focused exclusively on pediatric cases. We examined the relationship between switched memory B cells and clinical and immunologic manifestations of CVID in a pediatric population. Forty-five patients were evaluated. Patients were categorized as Group I (<5 switched memory B cells/ml, n = 24) or Group II (> or =5 switched memory B cells/mL, n = 21). CD3(+) T-cell counts and CD19(+) B-cell levels were lower among Group I patients. Only those in Group I had meningitis, sepsis, bronchiectasis, granulomatous lung disease, autoimmune cytopenias, or hematologic malignancies. Segregation of pediatric patients into high risk (Group I) and average risk (Group II) may assist in targeting surveillance appropriately.

Partial central diabetes insipidus in patient with common variable immunodeficiency

PubMed Central

Megías, Marta Cano; Matei, Ana Maria; Gonzalez Albarran, Olga; Perez Lopez, Gilberto

2012-01-01

Approximately 20% of patients with common variable immunodeficiency (CVID) have any autoimmune disease, as concurrent as prior to diagnosis, even during follow-up. In recent years, cases of CVID associated to endocrine autoimmune diseases have been reported. To our knowledge, no cases of CVID with diabetes insipidus has been reported previously. The authors present the case of a 37-year-old male, diagnosed of CVID, who had thirst, polyuria and nocturia for several years. After a water deprivation test and a complete resolution of patient’s symptoms with vasopressin (DDAVP) treatment, diagnosis of partial central diabetes insipidus was finally made. Patients diagnosed of CVID could develop water misbalance due to posterior hypophysis autoimmune disorder. A high index of clinical suspicion, an early diagnosis and treatment of these disease could avoid future complications and improve the quality of life of these patients. PMID:22761233

Perceived social support following percutaneous coronary intervention is a crucial factor in patients with coronary heart disease.

PubMed

Kähkönen, Outi; Kankkunen, Päivi; Miettinen, Heikki; Lamidi, Marja-Leena; Saaranen, Terhi

2017-05-01

To describe perceived social support among patients with coronary heart disease following percutaneous coronary intervention. A low level of social support is considered a risk factor for coronary heart disease in healthy individuals and reduces the likelihood that people diagnosed with coronary heart disease will have a good prognosis. A descriptive cross-sectional study. A survey of 416 patients was conducted in 2013. A self-report instrument, Social Support of People with Coronary Heart Disease, was used. The instrument comprises three dimensions of social support: informational, emotional, functional supports and 16 background variables. Data were analysed using descriptive statistics, factor analysis, mean sum variables and multivariate logistic regression. Perceived informational support was primarily high, but respondents' risk factors were not at the target level. The weakest items of informational support were advice on physical activity, continuum of care and rehabilitation. Regarding the items of emotional support, support from other cardiac patients was the weakest. The weakest item of functional support was respondents' sense of the healthcare professionals' care of patients coping with their disease. Background variables associated with perceived social support were gender, marital status, level of formal education, profession, physical activity, duration of coronary heart disease and previous myocardial infarction. Healthcare professionals should pay extra attention to women, single patients, physically inactive patients, those demonstrating a lower level of education, those with a longer duration of CHD, and respondents without previous acute myocardial infarction. Continuum of care and counselling are important to ensure especially among them. This study provides evidence that healthcare professionals should be more aware of the individual needs for social support among patients with coronary heart disease after percutaneous coronary intervention. © 2016 John Wiley & Sons Ltd.

The risk-adjusted vision beyond casemix (DRG) funding in Australia. International lessons in high complexity and capitation.

PubMed

Antioch, Kathryn M; Walsh, Michael K

2004-06-01

Hospitals throughout the world using funding based on diagnosis-related groups (DRG) have incurred substantial budgetary deficits, despite high efficiency. We identify the limitations of DRG funding that lack risk (severity) adjustment for State-wide referral services. Methods to risk adjust DRGs are instructive. The average price in casemix funding in the Australian State of Victoria is policy based, not benchmarked. Average cost weights are too low for high-complexity DRGs relating to State-wide referral services such as heart and lung transplantation and trauma. Risk-adjusted specified grants (RASG) are required for five high-complexity respiratory, cardiology and stroke DRGs incurring annual deficits of $3.6 million due to high casemix complexity and government under-funding despite high efficiency. Five stepwise linear regressions for each DRG excluded non-significant variables and assessed heteroskedasticity and multicollinearlity. Cost per patient was the dependent variable. Significant independent variables were age, length-of-stay outliers, number of disease types, diagnoses, procedures and emergency status. Diagnosis and procedure severity markers were identified. The methodology and the work of the State-wide Risk Adjustment Working Group can facilitate risk adjustment of DRGs State-wide and for Treasury negotiations for expenditure growth. The Alfred Hospital previously negotiated RASG of $14 million over 5 years for three trauma and chronic DRGs. Some chronic diseases require risk-adjusted capitation funding models for Australian Health Maintenance Organizations as an alternative to casemix funding. The use of Diagnostic Cost Groups can facilitate State and Federal government reform via new population-based risk adjusted funding models that measure health need.

Added Sugar Consumption and Chronic Oral Disease Burden among Adolescents in Brazil.

PubMed

Carmo, C D S; Ribeiro, M R C; Teixeira, J X P; Alves, C M C; Franco, M M; França, A K T C; Benatti, B B; Cunha-Cruz, J; Ribeiro, C C C

2018-05-01

Chronic oral diseases are rarely studied together, especially with an emphasis on their common risk factors. This study examined the association of added sugar consumption on "chronic oral disease burden" among adolescents, with consideration of obesity and systemic inflammation pathways through structural equation modeling. A cross-sectional study was conducted of a complex random sample of adolescent students enrolled at public schools in São Luís, Brazil ( n = 405). The outcome was chronic oral disease burden, a latent variable based on the presence of probing depth ≥4 mm, bleeding on probing, caries, and clinical consequences of untreated caries. The following hypotheses were tested: 1) caries and periodontal diseases among adolescents are correlated with each other; 2) added sugar consumption and obesity are associated with chronic oral disease burden; and 3) chronic oral disease burden is linked to systemic inflammation. Models were adjusted for socioeconomic status, added sugar consumption, oral hygiene behaviors, obesity, and serum levels of interleukin 6 (IL-6). All estimators of the latent variable chronic oral disease burden involved factor loadings ≥0.5 and P values <0.001, indicating good fit. Added sugar consumption (standardized coefficient [SC] = 0.212, P = 0.005), high IL-6 levels (SC = 0.130, P = 0.036), and low socioeconomic status (SC = -0.279, P = 0.001) were associated with increased chronic oral disease burden values. Obesity was associated with high IL-6 levels (SC = 0.232, P = 0.001). Visible plaque index was correlated with chronic oral disease burden (SC = 0.381, P < 0.001). Our finding that caries and periodontal diseases are associated with each other and with added sugar consumption, obesity, and systemic inflammation reinforces the guidance of the World Health Organization that any approach intended to prevent noncommunicable diseases should be directed toward common risk factors.

Oral candidiasis in systemic lupus erythematosus.

PubMed

Fangtham, M; Magder, L S; Petri, M A

2014-06-01

We assessed the frequency of oral candidiasis and the association between demographic variables, disease-related variables, corticosteroid treatment, other treatments and the occurrence of oral candidiasis in the Hopkins Lupus Cohort. In this large prospective cohort study of 2258 patients with systemic lupus erythematosus (SLE), demographic and clinical associates of oral candidiasis were estimated by univariate, multivariate and within-person regression models. There were 53,548 cohort visits. Oral candidiasis was diagnosed at 675 visits (1.25%) in 325 (14%) of the patients. In the multivariate analyses, oral candidiasis was associated with African-American ethnicity, SELENA-SLEDAI disease activity, high white blood cell count, a history of bacterial infection, prednisone use and immunosuppressive use. The urine protein by urine dip stick was higher in SLE patients with oral candidiasis. Considering only patients who had candidiasis at some visits in a 'within-person' analysis, candidiasis was more frequent in visits with higher SELENA-SLEDAI disease activity, high white blood cell count, proteinuria by urine dip stick, a history of bacterial infection and prednisone use. The use of hydroxychloroquine was associated with a lower risk of oral candidiasis, but was not statistically significant (p = 0.50) in the within-person analysis models. This study identified multiple risk factors for oral candidiasis in SLE. Inspection of the oral cavity for signs of oral candidiasis is recommended especially in SLE patients with active disease, proteinuria, high white blood cell count, taking prednisone, immunosuppressive drugs or antibiotics. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

One year in review 2016: systemic lupus erythematosus.

PubMed

Adinolfi, Antonella; Valentini, Eleonora; Calabresi, Emanuele; Tesei, Giulia; Signorini, Viola; Barsotti, Simone; Tani, Chiara

2016-01-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a highly variable course and prognosis. The management of the disease is still a clinical challenge for the treating physicians as many aspects regarding the disease pathogenesis, clinical picture and outcomes remain to be elucidated. New and interesting data are emerging; here the recent literature on SLE pathogenesis, clinical and laboratory aspects, as well as treatments and comorbidities, are reviewed and the main findings summarised in order to provide a bird's eye on the relevant papers on these topics.

Genome variability of foot-and-mouth disease virus during the short period of the 2010 epidemic in Japan.

PubMed

Nishi, Tatsuya; Yamada, Manabu; Fukai, Katsuhiko; Shimada, Nobuaki; Morioka, Kazuki; Yoshida, Kazuo; Sakamoto, Kenichi; Kanno, Toru; Yamakawa, Makoto

2017-02-01

Foot-and-mouth disease virus (FMDV) is highly contagious and has a high mutation rate, leading to extensive genetic variation. To investigate how FMDV genetically evolves over a short period of an epidemic after initial introduction into an FMD-free area, whole L-fragment sequences of 104 FMDVs isolated from the 2010 epidemic in Japan, which continued for less than three months were determined and phylogenetically and comparatively analyzed. Phylogenetic analysis of whole L-fragment sequences showed that these isolates were classified into a single group, indicating that FMDV was introduced into Japan in the epidemic via a single introduction. Nucleotide sequences of 104 virus isolates showed more than 99.56% pairwise identity rates without any genetic deletion or insertion, although no sequences were completely identical with each other. These results indicate that genetic substitutions of FMDV occurred gradually and constantly during the epidemic and generation of an extensive mutant virus could have been prevented by rapid eradication strategy. From comparative analysis of variability of each FMDV protein coding region, VP4 and 2C regions showed the highest average identity rates and invariant rates, and were confirmed as highly conserved. In contrast, the protein coding regions VP2 and VP1 were confirmed to be highly variable regions with the lowest average identity rates and invariant rates, respectively. Our data demonstrate the importance of rapid eradication strategy in an FMD epidemic and provide valuable information on the genome variability of FMDV during the short period of an epidemic. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene.

PubMed

Graul-Neumann, Luitgard M; Hausser, Ingrid; Essayie, Maximilian; Rauch, Anita; Kraus, Cornelia

2008-04-15

Autosomal dominant congenital cutis laxa (ADCL) is genetically heterogeneous and shows clinical variability. Only seven ADCL families with mutations in the elastin gene (ELN) have been described previously. We present morphological and molecular genetic studies in a cutis laxa kindred with a previously undescribed highly variable phenotype caused by a novel ELN mutation c.1621 C > T. The proband presented with severe cutis laxa, severe congenital lung disease previously undescribed in ADCL and pulmonary artery disease, which is often seen in ARCL but rare in ADCL. He also developed infantile spasms (OMIM 308350; West syndrome), which we consider a coincidental association although recessive cutis laxa or even digenic inheritance cannot be excluded. Electron microscopy of the proband's dermis revealed only mild rarefication of elastic fibers (in contrast to most recessive cutis laxa types). Apart from mild elastic fiber fragmentation, dermal morphology of the proband's father was within normal range. Molecular analysis of the ELN gene using genomic DNA from blood and RNA from cultured skin fibroblasts indicated a novel splice site mutation in the proband and his clinically healthy father. Analysis of ELN expression in fibroblasts provided evidence for a dominant-negative effect in the child, while due to an unknown mechanism, the father showed haploinsufficiency which might explain the significant clinical variability. Copyright 2008 Wiley-Liss, Inc.

High variability in baseline urinary free cortisol values in patients with Cushing's disease.

PubMed

Petersenn, S; Newell-Price, J; Findling, J W; Gu, F; Maldonado, M; Sen, K; Salgado, L R; Colao, A; Biller, B M K

2014-02-01

Twenty-four-hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's disease, we analysed baseline UFC in a large patient cohort with moderate-to-severe Cushing's disease and assessed whether variability correlates with hypercortisolism severity. These data will help clinicians establish the minimum number of UFC samples required to obtain reliable data. Observational study (enrolment phase of Phase III study). Patients (n = 152) with persistent/recurrent or de novo Cushing's disease and mean UFC (mUFC) ≥1·5×ULN (normal: 30-145 nmol/24 h) were included. Mean UFC level was calculated from four 24-h urine samples collected over 2 weeks. Over 600 24-h UFC samples were analysed. The mUFC levels of samples 1 and 2 and samples 3 and 4 were 1000 nmol/24 h (SD 1872) and 940 nmol/24 h (SD 2148), respectively; intrapatient coefficient of variation (CV) was 38% for mUFC. The intrapatient CV using all four samples was 52% (95% CI: 48-56). The intrapatient CV was 51% (95% CI: 44-58) for samples 1 and 2, 49% (95% CI: 43-56) for samples 3 and 4 and 54% (95% CI: 49-59) for samples 1, 2 and 3. Variability in mUFC increased as UFC levels increased. There were no correlations between UFC and clinical features of hypercortisolism. There is intrapatient variability of approximately 50% in 24-h UFC measurements, which is relevant to targets set to estimate any treatment effect. Analysing more than two 24-h collection periods in individual patients does not result in a relevant decrease in variability. Interestingly, UFC levels did not correlate with hypercortisolism severity. © 2013 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.

Resilience in women with autoimmune rheumatic diseases.

PubMed

Rojas, Manuel; Rodriguez, Yhojan; Pacheco, Yovana; Zapata, Elizabeth; Monsalve, Diana M; Mantilla, Rubén D; Rodríguez-Jimenez, Monica; Ramírez-Santana, Carolina; Molano-González, Nicolás; Anaya, Juan-Manuel

2017-12-28

To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (<48years) with systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis who had low socioeconomic status, whereas older patients (>50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Mortality determinants and prediction of outcome in high risk newborns.

PubMed

Dalvi, R; Dalvi, B V; Birewar, N; Chari, G; Fernandez, A R

1990-06-01

The aim of this study was to determine independent patient-related predictors of mortality in high risk newborns admitted at our centre. The study population comprised 100 consecutive newborns each, from the premature unit (PU) and sick baby care unit (SBCU), respectively. Thirteen high risk factors (variables) for each of the two units, were entered into a multivariate regression analysis. Variables with independent predictive value for poor outcome (i.e., death) in PU were, weight less than 1 kg, hyaline membrane disease, neurologic problems, and intravenous therapy. High risk factors in SBCU included, blood gas abnormality, bleeding phenomena, recurrent convulsions, apnea, and congenital anomalies. Identification of these factors guided us in defining priority areas for improvement in our system of neonatal care. Also, based on these variables a simple predictive score for outcome was constructed. The prediction equation and the score were cross-validated by applying them to a 'test-set' of 100 newborns each for PU and SBCU. Results showed a comparable sensitivity, specificity and error rate.

Heart rate variability in patients with systemic lupus erythematosus: a systematic review and methodological considerations.

PubMed

Matusik, P S; Matusik, P T; Stein, P K

2018-07-01

Aim The aim of this review was to summarize current knowledge about the scientific findings and potential clinical utility of heart rate variability measures in patients with systemic lupus erythematosus. Methods PubMed, Embase and Scopus databases were searched for the terms associated with systemic lupus erythematosus and heart rate variability, including controlled vocabulary, when appropriate. Articles published in English and available in full text were considered. Finally, 11 publications were selected, according to the systematic review protocol and were analyzed. Results In general, heart rate variability, measured in the time and frequency domains, was reported to be decreased in patients with systemic lupus erythematosus compared with controls. In some systemic lupus erythematosus studies, heart rate variability was found to correlate with inflammatory markers and albumin levels. A novel heart rate variability measure, heart rate turbulence onset, was shown to be increased, while heart rate turbulence slope was decreased in systemic lupus erythematosus patients. Reports of associations of changes in heart rate variability parameters with increasing systemic lupus erythematosus activity were inconsistent, showing decreasing heart rate variability or no relationship. However, the low/high frequency ratio was, in some studies, reported to increase with increasing disease activity or to be inversely correlated with albumin levels. Conclusions Patients with systemic lupus erythematosus have abnormal heart rate variability, which reflects cardiac autonomic dysfunction and may be related to inflammatory cytokines but not necessarily to disease activity. Thus measurement of heart rate variability could be a useful clinical tool for monitoring autonomic dysfunction in systemic lupus erythematosus, and may potentially provide prognostic information.

Disease Messaging in Churches: Implications for Health in African-American Communities

PubMed Central

Harmon, Brook E.; Chock, Marci; Brantley, Elizabeth; Wirth, Michael D.; Hébert, James R.

2016-01-01

Using the right messaging strategies, churches can help promote behavior change. Frequencies of disease-specific messages in 21 African-American churches were compared to overall and cancer-specific mortality and morbidity rates as well as church-level variables. Disease messages were found in 1025 of 2166 items. Frequently referenced topics included cancer (n=316), mental health conditions (n=253), heart disease (n=246), and infectious diseases (n=220). Messages for lung and colorectal cancers appeared at low frequency despite high mortality rates in African-American communities. Season, church size, and denomination showed significant associations with health messages. Next steps include testing messaging strategies aimed at improving the health of churchgoing communities. PMID:26296703

[Prostitutes of the east sector of Santiago: characteristics and pathology of sexual transmission].

PubMed

Medina, R; Mella, L; Espoz, H; Medina, E; Cumsille, F

1989-09-01

We studied the frequency of venereal disease in 329 prostitutes working at massage parlours in Santiago. The mean age was 24 years and half of them had high school or university studies. In spite of frequent sexual contacts averaging 2.8 per day, the prevalence of significant venereal disease was not high in this group. Notably, AIDS infection was not detected. Vaginitis due to Trichomonas or Candida infection was the commonest problem and this was half as frequent among gum preservative users. Marital condition, age, obstetrical history and other variables were not related to genital infection.

Added sugars and periodontal disease in young adults: an analysis of NHANES III data.

PubMed

Lula, Estevam C O; Ribeiro, Cecilia C C; Hugo, Fernando N; Alves, Cláudia M C; Silva, Antônio A M

2014-10-01

Added sugar consumption seems to trigger a hyperinflammatory state and may result in visceral adiposity, dyslipidemia, and insulin resistance. These conditions are risk factors for periodontal disease. However, the role of sugar intake in the cause of periodontal disease has not been adequately studied. We evaluated the association between the frequency of added sugar consumption and periodontal disease in young adults by using NHANES III data. Data from 2437 young adults (aged 18-25 y) who participated in NHANES III (1988-1994) were analyzed. We estimated the frequency of added sugar consumption by using food-frequency questionnaire responses. We considered periodontal disease to be present in teeth with bleeding on probing and a probing depth ≥3 mm at one or more sites. We evaluated this outcome as a discrete variable in Poisson regression models and as a categorical variable in multinomial logistic regression models adjusted for sex, age, race-ethnicity, education, poverty-income ratio, tobacco exposure, previous diagnosis of diabetes, and body mass index. A high consumption of added sugars was associated with a greater prevalence of periodontal disease in middle [prevalence ratio (PR): 1.39; 95% CI: 1.02, 1.89] and upper (PR: 1.42; 95% CI: 1.08, 1.85) tertiles of consumption in the adjusted Poisson regression model. The upper tertile of added sugar intake was associated with periodontal disease in ≥2 teeth (PR: 1.73; 95% CI: 1.19, 2.52) but not with periodontal disease in only one tooth (PR: 0.85; 95% CI: 0.54, 1.34) in the adjusted multinomial logistic regression model. A high frequency of consumption of added sugars is associated with periodontal disease, independent of traditional risk factors, suggesting that this consumption pattern may contribute to the systemic inflammation observed in periodontal disease and associated noncommunicable diseases. © 2014 American Society for Nutrition.

Cucurbit powdery mildews: Methodology for objective determination and denomination of races

USDA-ARS?s Scientific Manuscript database

Cucurbit powdery mildew (CPM), a disease on field and greenhouse cucurbit crops worldwide, is caused most frequently by two obligate erysiphaceous ectoparasites (Golovinomyces orontii s.l., Podosphaera xanthii) that are highly variable in their pathogenicity and virulence. Various, independent syste...

Adenosine stress cardiovascular magnetic resonance with variable-density spiral pulse sequences accurately detects coronary artery disease: initial clinical evaluation.

PubMed

Salerno, Michael; Taylor, Angela; Yang, Yang; Kuruvilla, Sujith; Ragosta, Michael; Meyer, Craig H; Kramer, Christopher M

2014-07-01

Adenosine stress cardiovascular magnetic resonance perfusion imaging can be limited by motion-induced dark-rim artifacts, which may be mistaken for true perfusion abnormalities. A high-resolution variable-density spiral pulse sequence with a novel density compensation strategy has been shown to reduce dark-rim artifacts in first-pass perfusion imaging. We aimed to assess the clinical performance of adenosine stress cardiovascular magnetic resonance using this new perfusion sequence to detect obstructive coronary artery disease. Cardiovascular magnetic resonance perfusion imaging was performed during adenosine stress (140 μg/kg per minute) and at rest on a Siemens 1.5-T Avanto scanner in 41 subjects with chest pain scheduled for coronary angiography. Perfusion images were acquired during injection of 0.1 mmol/kg Gadolinium-diethylenetriaminepentacetate at 3 short-axis locations using a saturation recovery interleaved variable-density spiral pulse sequence. Significant stenosis was defined as >50% by quantitative coronary angiography. Two blinded reviewers evaluated the perfusion images for the presence of adenosine-induced perfusion abnormalities and assessed image quality using a 5-point scale (1 [poor] to 5 [excellent]). The prevalence of obstructive coronary artery disease by quantitative coronary angiography was 68%. The average sensitivity, specificity, and accuracy were 89%, 85%, and 88%, respectively, with a positive predictive value and negative predictive value of 93% and 79%, respectively. The average image quality score was 4.4±0.7, with only 1 study with more than mild dark-rim artifacts. There was good inter-reader reliability with a κ statistic of 0.67. Spiral adenosine stress cardiovascular magnetic resonance results in high diagnostic accuracy for the detection of obstructive coronary artery disease with excellent image quality and minimal dark-rim artifacts. © 2014 American Heart Association, Inc.

Ambulatory blood pressure profiles in familial dysautonomia.

PubMed

Goldberg, Lior; Bar-Aluma, Bat-El; Krauthammer, Alex; Efrati, Ori; Sharabi, Yehonatan

2018-02-12

Familial dysautonomia (FD) is a rare genetic disease that involves extreme blood pressure fluctuations secondary to afferent baroreflex failure. The diurnal blood pressure profile, including the average, variability, and day-night difference, may have implications for long-term end organ damage. The purpose of this study was to describe the circadian pattern of blood pressure in the FD population and relationships with renal and pulmonary function, use of medications, and overall disability. We analyzed 24-h ambulatory blood pressure monitoring recordings in 22 patients with FD. Information about medications, disease severity, renal function (estimated glomerular filtration, eGFR), pulmonary function (forced expiratory volume in 1 s, FEV1) and an index of blood pressure variability (standard deviation of systolic pressure) were analyzed. The mean (± SEM) 24-h blood pressure was 115 ± 5.6/72 ± 2.0 mmHg. The diurnal blood pressure variability was high (daytime systolic pressure standard deviation 22.4 ± 1.5 mmHg, nighttime 17.2 ± 1.6), with a high frequency of a non-dipping pattern (16 patients, 73%). eGFR, use of medications, FEV1, and disability scores were unrelated to the degree of blood pressure variability or to dipping status. This FD cohort had normal average 24-h blood pressure, fluctuating blood pressure, and a high frequency of non-dippers. Although there was evidence of renal dysfunction based on eGFR and proteinuria, the ABPM profile was unrelated to the measures of end organ dysfunction or to reported disability.

Intraindividual variability as a marker of neurological dysfunction: a comparison of Alzheimer's disease and Parkinson's disease.

PubMed

Burton, Catherine L; Strauss, Esther; Hultsch, David F; Moll, Alex; Hunter, Michael A

2006-01-01

Individuals with certain neurological conditions may demonstrate greater inconsistency (i.e., intraindividual variability) on cognitive tasks compared to healthy controls. Several researchers have suggested that intraindividual variability may be a behavioral marker of compromised neurobiological mechanisms associated with aging, disease, or injury. The present study sought to investigate whether intraindividual variability is associated with general nervous system compromise, or rather, with certain types of neurological disturbances by comparing healthy adults, adults with Alzheimer's disease (AD), and Parkinson's disease (PD). Participants were assessed on four separate occasions using measures of reaction time and memory. Results indicated that inconsistency was correlated with indices of severity of impairment suggesting a dose-response relationship between cognitive disturbance and intraindividual variability: the more severe the cognitive disturbance, the greater the inconsistency. However, participants with AD were more inconsistent than those with PD, with both groups being more variable than the healthy group, even when controlling for group differences in overall severity of cognitive impairment or cognitive decline. Consequently, intraindividual variability may index both the severity of cognitive impairment and the nature of the neurological disturbance.

Utilizing Satellite Precipitation Products to Understand the Link Between Climate Variability and Malaria

NASA Astrophysics Data System (ADS)

Maggioni, V.; Mousam, A.; Delamater, P. L.; Cash, B. A.; Quispe, A.

2015-12-01

Malaria is a public health threat to people globally leading to 198 million cases and 584,000 deaths annually. Outbreaks of vector borne diseases such as malaria can be significantly impacted by climate variables such as precipitation. For example, an increase in rainfall has the potential to create pools of water that can serve as breeding locations for mosquitos. Peru is a country that is currently controlling malaria, but has not been able to completely eliminate the disease. Despite the various initiatives in order to control malaria - including regional efforts to improve surveillance, early detection, prompt treatment, and vector management - malaria cases in Peru have risen between 2011 and 2014. The purpose of this study is to test the hypothesis that climate variability plays a fundamental role in malaria occurrence over a 12-year period (2003-2014) in Peru. When analyzing climate variability, it is important to obtain high-quality, high-resolution data for a time series long enough to draw conclusion about how climate variables have been and are changing. Remote sensing is a powerful tool for measuring and monitoring climate variables continuously in time and space. A widely used satellite-based precipitation product, the Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA), available globally since 1998, was used to obtain 3-hourly data with a spatial resolution of 0.25° x 0.25°. The precipitation data was linked to weekly (2003-2014) malaria cases collected by health centers and available at a district level all over Peru to investigate the relationship between precipitation and the seasonal and annual variations in malaria incidence. Further studies will incorporate additional climate variables such as temperature, humidity, soil moisture, and surface pressure from remote sensing data products and climate models. Ultimately, this research will help us to understand if climate variability impacts malaria incidence rates and to determine which regions of the country are most affected.

Medication adherence and visit-to-visit variability of systolic blood pressure in African Americans with chronic kidney disease in the AASK trial.

PubMed

Hong, K; Muntner, P; Kronish, I; Shilane, D; Chang, T I

2016-01-01

Lower adherence to antihypertensive medications may increase visit-to-visit variability of blood pressure (VVV of BP), a risk factor for cardiovascular events and death. We used data from the African American Study of Kidney Disease and Hypertension (AASK) trial to examine whether lower medication adherence is associated with higher systolic VVV of BP in African Americans with hypertensive chronic kidney disease (CKD). Determinants of VVV of BP were also explored. AASK participants (n=988) were categorized by self-report or pill count as having perfect (100%), moderately high (75-99%), moderately low (50-74%) or low (<50%) proportion of study visits with high medication adherence over a 1-year follow-up period. We used multinomial logistic regression to examine determinants of medication adherence, and multivariable-adjusted linear regression to examine the association between medication adherence and systolic VVV of BP, defined as the coefficient of variation or the average real variability (ARV). Participants with lower self-reported adherence were generally younger and had a higher prevalence of comorbid conditions. Compared with perfect adherence, moderately high, moderately low and low adherence was associated with 0.65% (±0.31%), 0.99% (±0.31%) and 1.29% (±0.32%) higher systolic VVV of BP (defined as the coefficient of variation) in fully adjusted models. Results were qualitatively similar when using ARV or when using pill counts as the measure of adherence. Lower medication adherence is associated with higher systolic VVV of BP in African Americans with hypertensive CKD; efforts to improve medication adherence in this population may reduce systolic VVV of BP.

Clinical and genetic characterization of a founder PKHD1 mutation in Afrikaners with ARPKD.

PubMed

Lambie, Lindsay; Amin, Rasheda; Essop, Fahmida; Cnaan, Avital; Krause, Amanda; Guay-Woodford, Lisa M

2015-02-01

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) occurs in 1:20,000 live births. Disease expression is widely variable, with approximately 30 % of affected neonates dying perinatally, while others survive to adulthood. Mutations at the PKHD1 locus are responsible for all typical presentations. The objectives of this study were to define the clinical and genetic characteristics in a cohort of South African patients of Afrikaner origin, a population with a high prevalence of ARPKD. DNA from the cohort was analyzed for background haplotypes and the p.M627K mutation previously identified in two unrelated Afrikaner patients. The clinical phenotype of the homozygous group was characterized. Analysis of 36 Afrikaner families revealed that 27 patients, from 24 (67 %) families, were homozygous for the p.M627K substitution, occurring on a common haplotype. The clinical phenotype of the homozygous individuals was variable. Our data provide strong evidence that the p.M627K substitution is a founder mutation in the Afrikaner population and can be used for streamlined diagnostic testing for at-risk pregnancies. The observed clinical variability suggests that disease expression is modulated by other genetic loci or by gene-environment interactions.

Rumination time as a potential predictor of common diseases in high-productive Holstein dairy cows.

PubMed

Moretti, Riccardo; Biffani, Stefano; Tiezzi, Francesco; Maltecca, Christian; Chessa, Stefania; Bozzi, Riccardo

2017-11-01

We examined the hypothesis that rumination time (RT) could serve as a useful predictor of various common diseases of high producing dairy cows and hence improve herd management and animal wellbeing. We measured the changes in rumination time (RT) in the days before the recording of diseases (specifically: mastitis, reproductive system diseases, locomotor system issues, and gastroenteric diseases). We built predictive models to assess the association between RT and these diseases, using the former as the outcome variable, and to study the effects of the latter on the former. The average Pseudo-R 2 of the fitted models was moderate to low, and this could be due to the fact that RT is influenced by other additional factors which have a greater effect than the predictors used here. Although remaining in a moderate-to-low range, the average Pseudo-R 2 of the models regarding locomotion issues and gastroenteric diseases was higher than the others, suggesting the greater effect of these diseases on RT. The results are encouraging, but further work is needed if these models are to become useful predictors.

Evolution in health and medicine Sackler colloquium: Stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease.

PubMed

Feinberg, Andrew P; Irizarry, Rafael A

2010-01-26

Neo-Darwinian evolutionary theory is based on exquisite selection of phenotypes caused by small genetic variations, which is the basis of quantitative trait contribution to phenotype and disease. Epigenetics is the study of nonsequence-based changes, such as DNA methylation, heritable during cell division. Previous attempts to incorporate epigenetics into evolutionary thinking have focused on Lamarckian inheritance, that is, environmentally directed epigenetic changes. Here, we propose a new non-Lamarckian theory for a role of epigenetics in evolution. We suggest that genetic variants that do not change the mean phenotype could change the variability of phenotype; and this could be mediated epigenetically. This inherited stochastic variation model would provide a mechanism to explain an epigenetic role of developmental biology in selectable phenotypic variation, as well as the largely unexplained heritable genetic variation underlying common complex disease. We provide two experimental results as proof of principle. The first result is direct evidence for stochastic epigenetic variation, identifying highly variably DNA-methylated regions in mouse and human liver and mouse brain, associated with development and morphogenesis. The second is a heritable genetic mechanism for variable methylation, namely the loss or gain of CpG dinucleotides over evolutionary time. Finally, we model genetically inherited stochastic variation in evolution, showing that it provides a powerful mechanism for evolutionary adaptation in changing environments that can be mediated epigenetically. These data suggest that genetically inherited propensity to phenotypic variability, even with no change in the mean phenotype, substantially increases fitness while increasing the disease susceptibility of a population with a changing environment.

Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders.

PubMed

Posset, Roland; Garcia-Cazorla, Angeles; Valayannopoulos, Vassili; Teles, Elisa Leão; Dionisi-Vici, Carlo; Brassier, Anaïs; Burlina, Alberto B; Burgard, Peter; Cortès-Saladelafont, Elisenda; Dobbelaere, Dries; Couce, Maria L; Sykut-Cegielska, Jolanta; Häberle, Johannes; Lund, Allan M; Chakrapani, Anupam; Schiff, Manuel; Walter, John H; Zeman, Jiri; Vara, Roshni; Kölker, Stefan

2016-09-01

Patients with urea cycle disorders (UCDs) have an increased risk of neurological disease manifestation. Determining the effect of diagnostic and therapeutic interventions on the neurological outcome. Evaluation of baseline, regular follow-up and emergency visits of 456 UCD patients prospectively followed between 2011 and 2015 by the E-IMD patient registry. About two-thirds of UCD patients remained asymptomatic until age 12 days [i.e. the median age at diagnosis of patients identified by newborn screening (NBS)] suggesting a potential benefit of NBS. In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (>28 days), and a trend towards improved long-term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non-interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut-off level: 500 μmol/L) best predicted the neurological outcome. Promising results of NBS for late onset UCD patients are reported and should be re-evaluated in a larger and more advanced age group. However, non-interventional variables affect the neurological outcome of UCD patients. Available evidence-based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimised long-term and emergency treatment.

Effects of medical training scenarios on heart rate variability and motivation in students and simulated patients.

PubMed

Rieber, Nicole; Betz, Lisa; Enck, Paul; Muth, Eric; Nikendei, Christoph; Schrauth, Markus; Werner, Anne; Kowalski, Axel; Zipfel, Stephan

2009-06-01

Research regarding the experience of stress during medical training scenarios using standardised patients (SPs) has been primarily qualitative and has focused on the SPs. The purpose of this study was to quantitatively evaluate stress and motivation in both students and SPs during these scenarios by measuring heart rate variability (HRV) and administering the German version of the Questionnaire on Current Motivation (QCM). A total of 44 medical students (23 women, 21 men) participated in two medical history-taking training scenarios. In one scenario the SP role-played a patient with a somatic disease; in the other the SP played a patient with a psychosomatic disease, creating easy and difficult scenarios, respectively, for the student. Each student interviewed one of 11 SPs (five women, six men), using the same SP in both scenarios. Heart rate variability was measured during baseline periods and during the training scenarios in both students and SPs. Motivation was assessed before each training scenario. Heart rate variability was lower in both students and SPs during the scenarios compared with baseline values, but did not differ by scenario type. For students, motivation increased when the first scenario involved psychosomatic illness, but decreased when the first condition was somatic. For SPs motivation was consistent over time for scenarios involving psychosomatic disease, but decreased for somatic disease-related scenarios. The training scenarios induced stress in both students and SPs, as indicated by decreased HRV. Student motivation was high, indicating that SP scenarios represent a valid teaching method. Further studies in the natural setting of SP examinations are needed.

Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease.

PubMed

Spithoven, E M; Meijer, E; Borns, C; Boertien, W E; Gaillard, C A J M; Kappert, P; Greuter, M J W; van der Jagt, E; Vart, P; de Jong, P E; Gansevoort, R T

2016-03-01

Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBFMRI) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values. First, we validated RBFMRI measurement using phantoms simulating renal artery hemodynamics. Thereafter, we investigated in a test-set of 21 patients intra- and inter-observer coefficient of variation of RBFMRI. After validation, we measured RBFMRI in a cohort of 91 patients and compared the variability explained by characteristics indicative for disease severity for RBFMRI and RBF measured by continuous hippuran infusion. The correlation in flow measurement using phantoms by phase-contrast MRI was high and fluid collection was high (CCC=0.969). Technical problems that precluded RBFMRI measurement occurred predominantly in patients with a lower eGFR (34% vs. 16%). In subjects with higher eGFRs, variability in RBF explained by disease characteristics was similar for RBFMRI compared to RBFHip, whereas in subjects with lower eGFRs, this was significantly less for RBFMRI. Our study shows that RBF can be measured accurately in ADPKD patients by phase-contrast, but this technique may be less feasible in subjects with a lower eGFR. Renal blood flow (RBF) can be accurately measured by phase-contrast MRI in ADPKD patients. RBF measured by phase-contrast is associated with ADPKD disease severity. RBF measurement by phase-contrast MRI may be less feasible in patients with an impaired eGFR.

Construction and Use of Resting 12-Lead High Fidelity ECG "SuperScores" in Screening for Heart Disease

NASA Technical Reports Server (NTRS)

Schlegel, T. T.; Arenare, B.; Greco, E. C.; DePalma, J. L.; Starc, V.; Nunez, T.; Medina, R.; Jugo, D.; Rahman, M.A.; Delgado, R.

2007-01-01

We investigated the accuracy of several conventional and advanced resting ECG parameters for identifying obstructive coronary artery disease (CAD) and cardiomyopathy (CM). Advanced high-fidelity 12-lead ECG tests (approx. 5-min supine) were first performed on a "training set" of 99 individuals: 33 with ischemic or dilated CM and low ejection fraction (EF less than 40%); 33 with catheterization-proven obstructive CAD but normal EF; and 33 age-/gender-matched healthy controls. Multiple conventional and advanced ECG parameters were studied for their individual and combined retrospective accuracies in detecting underlying disease, the advanced parameters falling within the following categories: 1) Signal averaged ECG, including 12-lead high frequency QRS (150-250 Hz) plus multiple filtered and unfiltered parameters from the derived Frank leads; 2) 12-lead P, QRS and T-wave morphology via singular value decomposition (SVD) plus signal averaging; 3) Multichannel (12-lead, derived Frank lead, SVD lead) beat-to-beat QT interval variability; 4) Spatial ventricular gradient (and gradient component) variability; and 5) Heart rate variability. Several multiparameter ECG SuperScores were derivable, using stepwise and then generalized additive logistic modeling, that each had 100% retrospective accuracy in detecting underlying CM or CAD. The performance of these same SuperScores was then prospectively evaluated using a test set of another 120 individuals (40 new individuals in each of the CM, CAD and control groups, respectively). All 12-lead ECG SuperScores retrospectively generated for CM continued to perform well in prospectively identifying CM (i.e., areas under the ROC curve greater than 0.95), with one such score (containing just 4 components) maintaining 100% prospective accuracy. SuperScores retrospectively generated for CAD performed somewhat less accurately, with prospective areas under the ROC curve typically in the 0.90-0.95 range. We conclude that resting 12-lead high-fidelity ECG employing and combining the results of several advanced ECG software techniques shows great promise as a rapid and inexpensive tool for screening of heart disease.

[Modelling the effect of local climatic variability on dengue transmission in Medellin (Colombia) by means of time series analysis].

PubMed

Rúa-Uribe, Guillermo L; Suárez-Acosta, Carolina; Chauca, José; Ventosilla, Palmira; Almanza, Rita

2013-09-01

Dengue fever is a major impact on public health vector-borne disease, and its transmission is influenced by entomological, sociocultural and economic factors. Additionally, climate variability plays an important role in the transmission dynamics. A large scientific consensus has indicated that the strong association between climatic variables and disease could be used to develop models to explain the incidence of the disease. To develop a model that provides a better understanding of dengue transmission dynamics in Medellin and predicts increases in the incidence of the disease. The incidence of dengue fever was used as dependent variable, and weekly climatic factors (maximum, mean and minimum temperature, relative humidity and precipitation) as independent variables. Expert Modeler was used to develop a model to better explain the behavior of the disease. Climatic variables with significant association to the dependent variable were selected through ARIMA models. The model explains 34% of observed variability. Precipitation was the climatic variable showing statistically significant association with the incidence of dengue fever, but with a 20 weeks delay. In Medellin, the transmission of dengue fever was influenced by climate variability, especially precipitation. The strong association dengue fever/precipitation allowed the construction of a model to help understand dengue transmission dynamics. This information will be useful to develop appropriate and timely strategies for dengue control.

Bayesian dynamic modeling of time series of dengue disease case counts.

PubMed

Martínez-Bello, Daniel Adyro; López-Quílez, Antonio; Torres-Prieto, Alexander

2017-07-01

The aim of this study is to model the association between weekly time series of dengue case counts and meteorological variables, in a high-incidence city of Colombia, applying Bayesian hierarchical dynamic generalized linear models over the period January 2008 to August 2015. Additionally, we evaluate the model's short-term performance for predicting dengue cases. The methodology shows dynamic Poisson log link models including constant or time-varying coefficients for the meteorological variables. Calendar effects were modeled using constant or first- or second-order random walk time-varying coefficients. The meteorological variables were modeled using constant coefficients and first-order random walk time-varying coefficients. We applied Markov Chain Monte Carlo simulations for parameter estimation, and deviance information criterion statistic (DIC) for model selection. We assessed the short-term predictive performance of the selected final model, at several time points within the study period using the mean absolute percentage error. The results showed the best model including first-order random walk time-varying coefficients for calendar trend and first-order random walk time-varying coefficients for the meteorological variables. Besides the computational challenges, interpreting the results implies a complete analysis of the time series of dengue with respect to the parameter estimates of the meteorological effects. We found small values of the mean absolute percentage errors at one or two weeks out-of-sample predictions for most prediction points, associated with low volatility periods in the dengue counts. We discuss the advantages and limitations of the dynamic Poisson models for studying the association between time series of dengue disease and meteorological variables. The key conclusion of the study is that dynamic Poisson models account for the dynamic nature of the variables involved in the modeling of time series of dengue disease, producing useful models for decision-making in public health.

Comparison of small-area deprivation measures as predictors of chronic disease burden in a low-income population.

PubMed

Lòpez-De Fede, Ana; Stewart, John E; Hardin, James W; Mayfield-Smith, Kathy

2016-06-10

Measures of small-area deprivation may be valuable in geographically targeting limited resources to prevent, diagnose, and effectively manage chronic conditions in vulnerable populations. We developed a census-based small-area socioeconomic deprivation index specifically to predict chronic disease burden among publically insured Medicaid recipients in South Carolina, a relatively poor state in the southern United States. We compared the predictive ability of the new index with that of four other small-area deprivation indicators. To derive the ZIP Code Tabulation Area-Level Palmetto Small-Area Deprivation Index (Palmetto SADI), we evaluated ten census variables across five socioeconomic deprivation domains, identifying the combination of census indicators most highly correlated with a set of five chronic disease conditions among South Carolina Medicaid enrollees. In separate validation studies, we used both logistic and spatial regression methods to assess the ability of Palmetto SADI to predict chronic disease burden among state Medicaid recipients relative to four alternative small-area socioeconomic deprivation measures: the Townsend index of material deprivation; a single-variable poverty indicator; and two small-area designations of health care resource deprivation, Primary Care Health Professional Shortage Area and Medically Underserved Area/Medically Underserved Population. Palmetto SADI was the best predictor of chronic disease burden (presence of at least one condition and presence of two or more conditions) among state Medicaid recipients compared to all alternative deprivation measures tested. A low-cost, regionally optimized socioeconomic deprivation index, Palmetto SADI can be used to identify areas in South Carolina at high risk for chronic disease burden among Medicaid recipients and other low-income Medicaid-eligible populations for targeted prevention, screening, diagnosis, disease self-management, and care coordination activities.

Climate variability and change in the United States: potential impacts on vector- and rodent-borne diseases.

PubMed Central

Gubler, D J; Reiter, P; Ebi, K L; Yap, W; Nasci, R; Patz, J A

2001-01-01

Diseases such as plague, typhus, malaria, yellow fever, and dengue fever, transmitted between humans by blood-feeding arthropods, were once common in the United States. Many of these diseases are no longer present, mainly because of changes in land use, agricultural methods, residential patterns, human behavior, and vector control. However, diseases that may be transmitted to humans from wild birds or mammals (zoonoses) continue to circulate in nature in many parts of the country. Most vector-borne diseases exhibit a distinct seasonal pattern, which clearly suggests that they are weather sensitive. Rainfall, temperature, and other weather variables affect in many ways both the vectors and the pathogens they transmit. For example, high temperatures can increase or reduce survival rate, depending on the vector, its behavior, ecology, and many other factors. Thus, the probability of transmission may or may not be increased by higher temperatures. The tremendous growth in international travel increases the risk of importation of vector-borne diseases, some of which can be transmitted locally under suitable circumstances at the right time of the year. But demographic and sociologic factors also play a critical role in determining disease incidence, and it is unlikely that these diseases will cause major epidemics in the United States if the public health infrastructure is maintained and improved. PMID:11359689

Understanding the Effects of Genotype, Growing Year, and Breeding on Tunisian Durum Wheat Allergenicity. 2. The Celiac Disease Case.

PubMed

Boukid, Fatma; Prandi, Barbara; Sforza, Stefano; Sayar, Rhouma; Seo, Yong Weon; Mejri, Mondher; Yacoubi, Ines

2017-07-19

The aim of this study was to compare immunogenic and toxic gluten peptides related to celiac disease (CD). 100 accessions of genotypes selected during the 20th century in Tunisia were in vitro digested and then analyzed by UPLC/ESI-MS technique using an isotopically labeled internal standard. The first MANOVA confirmed a high variability in the content of immunogenic and toxic peptides reflecting high genetic diversity in the germplasm released during the past century in Tunisia, consistently with PCA and clustering analysis results. Our finding showed also important variability in CD epitopes due to growing season's climate scenarios. Moreover, the second MANOVA revealed significant differences between abandoned and modern cultivars' CD-related peptide amounts. Although we could not conclude that there was an augment of allergens in newly selected durum wheat lines compared to abandoned ones, we demonstrated that modern genotype peptides were less sensitive to climate variation, which is a useful indicator for wheat breeders.

Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism.

PubMed

de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; de Mattos, Cinara Cássia Brandão; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

2015-01-01

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region--rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD.

Visit-to-visit blood pressure variability as a prognostic marker in patients with cardiovascular and cerebrovascular diseases--relationships and comparisons with vascular markers of atherosclerosis.

PubMed

Lau, Kui Kai; Wong, Yuen Kwun; Chan, Yap Hang; Teo, Kay Cheong; Chan, Koon Ho; Wai Li, Leonard Sheung; Cheung, Raymond Tak Fai; Siu, Chung Wah; Ho, Shu Leong; Tse, Hung Fat

2014-07-01

Visit-to-visit blood pressure variability (BPV) is a simple surrogate marker for the development of atherosclerotic diseases, cardiovascular and all-cause mortality. Nevertheless, the relative prognostic value of BPV in comparison with other established vascular assessments remain uncertain. We prospectively followed-up 656 high-risk patients with diabetes or established cardiovascular or cerebrovascular diseases for the occurrence of major adverse cardiovascular events (MACEs). Baseline brachial endothelial function, carotid intima-media thickness (IMT) and plaque burden, ankle-brachial index and arterial stiffness were determined. Visit-to-visit BPV were recorded during a mean 18 ± 9 outpatient clinic visits. After a mean 81 ± 12 month's follow-up, 123 patients (19%) developed MACEs. Patients who developed a MACE had significantly higher systolic BPV, more severe endothelial function, arterial stiffness and systemic atherosclerotic burden compared to patients who did not develop a MACE (all P<0.01). BPV significantly correlated with all of the vascular assessments (P<0.01). A high carotid IMT had the greatest prognostic value in predicting development of a MACE (area under receiver operating characteristic curve (AUC) 0.69 ± 0.03, P<0.01). A high BPV also had moderate prognostic value in prediction of MACE (AUC 0.65 ± 0.03, P<0.01). After adjustment of confounding factors, a high BPV remained a significant independent predictor of MACE (hazards ratio 1.67, 95% confidence interval 1.14-2.43, P<0.01). Compared with established surrogate markers of atherosclerosis, visit-to-visit BPV provides similar prognostic information and may represent a new and simple marker for adverse outcomes in patients with vascular diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Relationship between heart rate variability and pulse wave velocity and their association with patient outcomes in chronic kidney disease

PubMed Central

Chandra, Preeti; Sands, Robin L.; Gillespie, Brenda W.; Levin, Nathan W.; Kotanko, Peter; Kiser, Margaret; Finkelstein, Fredric; Hinderliter, Alan; Rajagopalan, Sanjay; Sengstock, David; Saran, Rajiv

2014-01-01

Background: Arterial stiffness and low heart rate variability (HRV) have each been associated with increased cardiovascular risk in a variety of patient populations. We explored the relationship between HRV and pulse wave velocity (PWV measure of arterial stiffness) in patients with chronic kidney disease (CKD prior to ESRD) along with examining their association with the outcomes of cardiovascular disease (CVD), death, and progression to end stage renal disease (ESRD). Methods: The RRI-CKD Study is a 4-center prospective cohort study of CKD stages 3 – 5 (n = 834). A subset underwent both HRV testing by 24-hour Holter and carotid-femoral PWV (n = 240). Multiple linear regression was used to assess predictors of PWV and Cox regression to investigate the association of HRV and PWV with time to first CVD event or death and ESRD. Results: Although several HRV measures were inversely correlated with PWV, this association was attenuated after adjustment for age and/or diabetes and no longer significant after adjustment for C-reactive protein. Low HRV and high PWV were individually associated with increased risk of the composite endpoint of CVD/death in multivariable analysis. The risk of the composite of CVD/death was highest for patients with both low HRV and high PWV. Conclusion: Age, diabetes, and inflammation together explained the inverse association between HRV and PWV. Inflammation may play a role in the pathogenesis of both low HRV and high PWV. The combination of low HRV and high PWV showed the strongest association with a composite CVD outcome. Mechanisms underlying abnormalities in PWV and HRV, and the role of these measures as intermediate outcomes in future trials in CKD patients, merit further study. PMID:24356038

The reliability of alcoholism history in patients with alcohol-related cirrhosis.

PubMed

Yates, W R; Labrecque, D R; Pfab, D

1998-01-01

Alcoholic liver disease is considered an indication for liver transplantation when a candidate is felt to have a high likelihood of abstinence following transplantation. Historical variables such as duration of sobriety, duration and quantity of drinking, and treatment history are commonly used to estimate alcoholism prognosis, yet their reliability and validity in patients with alcoholic cirrhosis has received limited study. Fifty subjects (9 women and 41 men) with alcoholic cirrhosis underwent an alcoholism history interview. Each subject had a collateral source (usually a spouse) who was interviewed by a second interviewer blind to the subject's alcoholism history. The two histories were compared for duration of abstinence in months and estimated alcoholism relapse risk was calculated using the High-risk Alcoholism Relapse scale (HRAR). Duration of sobriety correlated highly between subject and collateral source (Spearman r= 0.96, P = 0.0001) as did HRAR total score (Spearman r = 0.72, P = 0.0001). Categorical assignments also showed high correlations with duration of sobriety (kappa = 0.97) and HRAR category (kappa = 0.63). When disagreements were present, collateral sources tended to underestimate severity of alcoholism. We conclude that patients with alcoholic liver disease provide a reliable history for alcoholism variables when compared with a collateral source, and that, when disagreements are present, subjects tend to report a more acute or severe alcohol problem. The results support the clinical use of patient history information in making decisions about medical interventions for alcoholic liver disease.

Interannual variability of human plague occurrence in the Western United States explained by tropical and North Pacific Ocean climate variability.

PubMed

Ari, Tamara Ben; Gershunov, Alexander; Tristan, Rouyer; Cazelles, Bernard; Gage, Kenneth; Stenseth, Nils C

2010-09-01

Plague is a vector-borne, highly virulent zoonotic disease caused by the bacterium Yersinia pestis. It persists in nature through transmission between its hosts (wild rodents) and vectors (fleas). During epizootics, the disease expands and spills over to other host species such as humans living in or close to affected areas. Here, we investigate the effect of large-scale climate variability on the dynamics of human plague in the western United States using a 56-year time series of plague reports (1950-2005). We found that El Niño Southern Oscillation and Pacific Decadal Oscillation in combination affect the dynamics of human plague over the western United States. The underlying mechanism could involve changes in precipitation and temperatures that impact both hosts and vectors. It is suggested that snow also may play a key role, possibly through its effects on summer soil moisture, which is known to be instrumental for flea survival and development and sustained growth of vegetation for rodents.

Nonlocal Intracranial Cavity Extraction

PubMed Central

Manjón, José V.; Eskildsen, Simon F.; Coupé, Pierrick; Romero, José E.; Collins, D. Louis; Robles, Montserrat

2014-01-01

Automatic and accurate methods to estimate normalized regional brain volumes from MRI data are valuable tools which may help to obtain an objective diagnosis and followup of many neurological diseases. To estimate such regional brain volumes, the intracranial cavity volume (ICV) is often used for normalization. However, the high variability of brain shape and size due to normal intersubject variability, normal changes occurring over the lifespan, and abnormal changes due to disease makes the ICV estimation problem challenging. In this paper, we present a new approach to perform ICV extraction based on the use of a library of prelabeled brain images to capture the large variability of brain shapes. To this end, an improved nonlocal label fusion scheme based on BEaST technique is proposed to increase the accuracy of the ICV estimation. The proposed method is compared with recent state-of-the-art methods and the results demonstrate an improved performance both in terms of accuracy and reproducibility while maintaining a reduced computational burden. PMID:25328511

The use of heart rate turbulence and heart rate variability in the assessment of autonomic regulation and circadian rhythm in patients with systemic lupus erythematosus without apparent heart disease.

PubMed

Poliwczak, A R; Waszczykowska, E; Dziankowska-Bartkowiak, B; Koziróg, M; Dworniak, K

2018-03-01

Background Systemic lupus erythematosus is a progressive autoimmune disease. There are reports suggesting that patients even without overt signs of cardiovascular complications have impaired autonomic function. The aim of this study was to assess autonomic function using heart rate turbulence and heart rate variability parameters indicated in 24-hour ECG Holter monitoring. Methods Twenty-six women with systemic lupus erythematosus and 30 healthy women were included. Twenty-four hour ambulatory ECG-Holter was performed in home conditions. The basic parameters of heart rate turbulence and heart rate variability were calculated. The analyses were performed for the entire day and separately for daytime activity and night time rest. Results There were no statistically significant differences in the basic anthropometric parameters. The mean duration of disease was 11.52 ± 7.42. There was a statistically significant higher turbulence onset (To) value in patients with systemic lupus erythematosus, median To = -0.17% (minimum -1.47, maximum 3.0) versus To = -1.36% (minimum -4.53, maximum -0.41), P < 0.001. There were no such differences for turbulence slope (Ts). In the 24-hour analysis almost all heart rate variability parameters were significantly lower in the systemic lupus erythematosus group than in the healthy controls, including SDANN and r-MSSD and p50NN. Concerning the morning activity and night resting periods, the results were similar as for the whole day. In the control group, higher values in morning activity were noted for parameters that characterise sympathetic activity, especially SDANN, and were significantly lower for parasympathetic parameters, including r-MSSD and p50NN, which prevailed at night. There were no statistically significant changes for systemic lupus erythematosus patients for p50NN and low and very low frequency. There was a positive correlation between disease duration and SDNN, R = 0.417; P < 0.05 and SDANN, R = 0.464; P < 0.05, a negative correlation between low/high frequency ratio and r-MSSD, R = -0.454; P < 0.05; p50NN, R = -0.435; P < 0.05 and high frequency, R = -0.478; P < 0.05. In contrast, there was no statistically significant correlation between heart rate turbulence and other variables evaluated, including disease duration and the type of autoantibodies. Our study confirms the presence of autonomic disorders with respect to both heart rate variability and heart rate turbulence parameters and the presence of diurnal disturbances of sympathetic-parasympathetic balance. Further studies are required.

Disease phobia and disease conviction are separate dimensions underlying hypochondriasis.

PubMed

Fergus, Thomas A; Valentiner, David P

2010-12-01

The current study uses data from a large nonclinical college student sample (N = 503) to examine a structural model of hypochondriasis (HC). This model predicts the distinctiveness of two dimensions (disease phobia and disease conviction) purported to underlie the disorder, and that these two dimensions are differentially related to variables important to health anxiety and somatoform disorders, respectively. Results were generally consistent with the hypothesized model. Specifically, (a) body perception variables (somatosensory amplification and anxiety sensitivity - physical) emerged as significant predictors of disease phobia, but not disease conviction; (b) emotion dysregulation variables (cognitive avoidance and cognitive reappraisal) emerged as significant predictors of disease conviction, but not disease phobia; and (c) both disease phobia and disease conviction independently predicted medical utilization. Further, collapsing disease phobia and disease conviction onto a single latent factor provided an inadequate fit to the data. Conceptual and therapeutic implications of these results are discussed. 2010 Elsevier Ltd. All rights reserved.

Full Genome Sequencing Reveals New Southern African Territories Genotypes Bringing Us Closer to Understanding True Variability of Foot-and-Mouth Disease Virus in Africa

PubMed Central

Lasecka-Dykes, Lidia; Wright, Caroline F.; Di Nardo, Antonello; Logan, Grace; Mioulet, Valerie; Jackson, Terry; Tuthill, Tobias J.; Knowles, Nick J.; King, Donald P.

2018-01-01

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hooved animals that poses a constant burden on farmers in endemic regions and threatens the livestock industries in disease-free countries. Despite the increased number of publicly available whole genome sequences, FMDV data are biased by the opportunistic nature of sampling. Since whole genomic sequences of Southern African Territories (SAT) are particularly underrepresented, this study sequenced 34 isolates from eastern and southern Africa. Phylogenetic analyses revealed two novel genotypes (that comprised 8/34 of these SAT isolates) which contained unusual 5′ untranslated and non-structural encoding regions. While recombination has occurred between these sequences, phylogeny violation analyses indicated that the high degree of sequence diversity for the novel SAT genotypes has not solely arisen from recombination events. Based on estimates of the timing of ancestral divergence, these data are interpreted as being representative of un-sampled FMDV isolates that have been subjected to geographical isolation within Africa by the effects of the Great African Rinderpest Pandemic (1887–1897), which caused a mass die-out of FMDV-susceptible hosts. These findings demonstrate that further sequencing of African FMDV isolates is likely to reveal more unusual genotypes and will allow for better understanding of natural variability and evolution of FMDV. PMID:29652800

Genetic diversity and phylogeography of highly zoonotic Echinococcus granulosus genotype G1 in the Americas (Argentina, Brazil, Chile and Mexico) based on 8279bp of mtDNA.

PubMed

Laurimäe, Teivi; Kinkar, Liina; Andresiuk, Vanessa; Haag, Karen Luisa; Ponce-Gordo, Francisco; Acosta-Jamett, Gerardo; Garate, Teresa; Gonzàlez, Luis Miguel; Saarma, Urmas

2016-11-01

Echinococcus granulosus is a taeniid cestode and the etiological agent of an infectious zoonotic disease known as cystic echinococcosis (CE) or hydatid disease. CE is a serious public health concern in many parts of the world, including the Americas, where it is highly endemic in many regions. Echinococcus granulosus displays high intraspecific genetic variability and is divided into multiple genotypes (G1-G8, G10) with differences in their biology and etiology. Of these, genotype G1 is responsible for the majority of human and livestock infections and has the broadest host spectrum. However, despite the high significance to the public and livestock health, the data on genetic variability and regional genetic differences of genotype G1 in America are scarce. The aim of this study was to evaluate the genetic variability and phylogeography of G1 in several countries in America by sequencing a large portion of the mitochondrial genome. We analysed 8279bp of mtDNA for 52 E. granulosus G1 samples from sheep, cattle and pigs collected in Argentina, Brazil, Chile and Mexico, covering majority of countries in the Americas where G1 has been reported. The phylogenetic network revealed 29 haplotypes and a high haplotype diversity (Hd=0.903). The absence of phylogeographic segregation between different regions in America suggests the importance of animal transportation in shaping the genetic structure of E. granulosus G1. In addition, our study revealed many highly divergent haplotypes, indicating a long and complex evolutionary history of E. granulosus G1 in the Americas. Copyright © 2016 Elsevier B.V. All rights reserved.

A Study of Effects of MultiCollinearity in the Multivariable Analysis

PubMed Central

Yoo, Wonsuk; Mayberry, Robert; Bae, Sejong; Singh, Karan; (Peter) He, Qinghua; Lillard, James W.

2015-01-01

A multivariable analysis is the most popular approach when investigating associations between risk factors and disease. However, efficiency of multivariable analysis highly depends on correlation structure among predictive variables. When the covariates in the model are not independent one another, collinearity/multicollinearity problems arise in the analysis, which leads to biased estimation. This work aims to perform a simulation study with various scenarios of different collinearity structures to investigate the effects of collinearity under various correlation structures amongst predictive and explanatory variables and to compare these results with existing guidelines to decide harmful collinearity. Three correlation scenarios among predictor variables are considered: (1) bivariate collinear structure as the most simple collinearity case, (2) multivariate collinear structure where an explanatory variable is correlated with two other covariates, (3) a more realistic scenario when an independent variable can be expressed by various functions including the other variables. PMID:25664257

A Study of Effects of MultiCollinearity in the Multivariable Analysis.

PubMed

Yoo, Wonsuk; Mayberry, Robert; Bae, Sejong; Singh, Karan; Peter He, Qinghua; Lillard, James W

2014-10-01

A multivariable analysis is the most popular approach when investigating associations between risk factors and disease. However, efficiency of multivariable analysis highly depends on correlation structure among predictive variables. When the covariates in the model are not independent one another, collinearity/multicollinearity problems arise in the analysis, which leads to biased estimation. This work aims to perform a simulation study with various scenarios of different collinearity structures to investigate the effects of collinearity under various correlation structures amongst predictive and explanatory variables and to compare these results with existing guidelines to decide harmful collinearity. Three correlation scenarios among predictor variables are considered: (1) bivariate collinear structure as the most simple collinearity case, (2) multivariate collinear structure where an explanatory variable is correlated with two other covariates, (3) a more realistic scenario when an independent variable can be expressed by various functions including the other variables.

Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

PubMed

Yang, Lun; Price, Elvin T; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

2013-01-01

Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

PubMed Central

Buchhorn, Reiner; Meint, Sebastian

2016-01-01

Introduction Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Results Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. Conclusion It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children—allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)—have the highest risk for ‘stress diseases’ such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children. PMID:27861527

Quantitative assessment of finger tapping characteristics in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease.

PubMed

Roalf, David R; Rupert, Petra; Mechanic-Hamilton, Dawn; Brennan, Laura; Duda, John E; Weintraub, Daniel; Trojanowski, John Q; Wolk, David; Moberg, Paul J

2018-06-01

Fine motor impairments are common in neurodegenerative disorders, yet standardized, quantitative measurements of motor abilities are uncommonly used in neurological practice. Thus, understanding and comparing fine motor abilities across disorders have been limited. The current study compared differences in finger tapping, inter-tap interval, and variability in Alzheimer's disease (AD), Parkinson's disease (PD), mild cognitive impairment (MCI), and healthy older adults (HOA). Finger tapping was measured using a highly sensitive light-diode finger tapper. Total number of finger taps, inter-tap interval, and intra-individual variability (IIV) of finger tapping was measured and compared in AD (n = 131), PD (n = 63), MCI (n = 46), and HOA (n = 62), controlling for age and sex. All patient groups had fine motor impairments relative to HOA. AD and MCI groups produced fewer taps with longer inter-tap interval and higher IIV compared to HOA. The PD group, however, produced more taps with shorter inter-tap interval and higher IIV compared to HOA. Disease-specific changes in fine motor function occur in the most common neurodegenerative diseases. The findings suggest that alterations in finger tapping patterns are common in AD, MCI, and PD. In addition, the present results underscore the importance of motor dysfunction even in neurodegenerative disorders without primary motor symptoms.

Bacterial community variation in human body habitats across space and time.

PubMed

Costello, Elizabeth K; Lauber, Christian L; Hamady, Micah; Fierer, Noah; Gordon, Jeffrey I; Knight, Rob

2009-12-18

Elucidating the biogeography of bacterial communities on the human body is critical for establishing healthy baselines from which to detect differences associated with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in seven to nine healthy adults on four occasions. We found that community composition was determined primarily by body habitat. Within habitats, interpersonal variability was high, whereas individuals exhibited minimal temporal variability. Several skin locations harbored more diverse communities than the gut and mouth, and skin locations differed in their community assembly patterns. These results indicate that our microbiota, although personalized, varies systematically across body habitats and time; such trends may ultimately reveal how microbiome changes cause or prevent disease.

Bacterial Community Variation in Human Body Habitats Across Space and Time

PubMed Central

Costello, Elizabeth K.; Lauber, Christian L.; Hamady, Micah; Fierer, Noah; Gordon, Jeffrey I.; Knight, Rob

2010-01-01

Elucidating the biogeography of bacterial communities on the human body is critical for establishing healthy baselines from which to detect differences associated with diseases. To obtain an integrated view of the spatial and temporal distribution of the human microbiota, we surveyed bacteria from up to 27 sites in 7–9 healthy adults on four occasions. We found that community composition was determined primarily by body habitat. Within habitats, interpersonal variability was high, while individuals exhibited minimal temporal variability. Several skin locations harbored more diverse communities than the gut and mouth, and skin locations differed in their community assembly patterns. These results indicate that our microbiota, although personalized, varies systematically across body habitats and time: such trends may ultimately reveal how microbiome changes cause or prevent disease. PMID:19892944

Climate Teleconnections and Recent Patterns of Human and Animal Disease Outbreaks

PubMed Central

Anyamba, Assaf; Linthicum, Kenneth J.; Small, Jennifer L.; Collins, Kathrine M.; Tucker, Compton J.; Pak, Edwin W.; Britch, Seth C.; Eastman, James Ronald; Pinzon, Jorge E.; Russell, Kevin L.

2012-01-01

Background Recent clusters of outbreaks of mosquito-borne diseases (Rift Valley fever and chikungunya) in Africa and parts of the Indian Ocean islands illustrate how interannual climate variability influences the changing risk patterns of disease outbreaks. Although Rift Valley fever outbreaks have been known to follow periods of above-normal rainfall, the timing of the outbreak events has largely been unknown. Similarly, there is inadequate knowledge on climate drivers of chikungunya outbreaks. We analyze a variety of climate and satellite-derived vegetation measurements to explain the coupling between patterns of climate variability and disease outbreaks of Rift Valley fever and chikungunya. Methods and Findings We derived a teleconnections map by correlating long-term monthly global precipitation data with the NINO3.4 sea surface temperature (SST) anomaly index. This map identifies regional hot-spots where rainfall variability may have an influence on the ecology of vector borne disease. Among the regions are Eastern and Southern Africa where outbreaks of chikungunya and Rift Valley fever occurred 2004–2009. Chikungunya and Rift Valley fever case locations were mapped to corresponding climate data anomalies to understand associations between specific anomaly patterns in ecological and climate variables and disease outbreak patterns through space and time. From these maps we explored associations among Rift Valley fever disease occurrence locations and cumulative rainfall and vegetation index anomalies. We illustrated the time lag between the driving climate conditions and the timing of the first case of Rift Valley fever. Results showed that reported outbreaks of Rift Valley fever occurred after ∼3–4 months of sustained above-normal rainfall and associated green-up in vegetation, conditions ideal for Rift Valley fever mosquito vectors. For chikungunya we explored associations among surface air temperature, precipitation anomalies, and chikungunya outbreak locations. We found that chikungunya outbreaks occurred under conditions of anomalously high temperatures and drought over Eastern Africa. However, in Southeast Asia, chikungunya outbreaks were negatively correlated (p<0.05) with drought conditions, but positively correlated with warmer-than-normal temperatures and rainfall. Conclusions/Significance Extremes in climate conditions forced by the El Niño/Southern Oscillation (ENSO) lead to severe droughts or floods, ideal ecological conditions for disease vectors to emerge, and may result in epizootics and epidemics of Rift Valley fever and chikungunya. However, the immune status of livestock (Rift Valley fever) and human (chikungunya) populations is a factor that is largely unknown but very likely plays a role in the spatial-temporal patterns of these disease outbreaks. As the frequency and severity of extremes in climate increase, the potential for globalization of vectors and disease is likely to accelerate. Understanding the underlying patterns of global and regional climate variability and their impacts on ecological drivers of vector-borne diseases is critical in long-range planning of appropriate disease and disease-vector response, control, and mitigation strategies. PMID:22292093

Climate teleconnections and recent patterns of human and animal disease outbreaks.

PubMed

Anyamba, Assaf; Linthicum, Kenneth J; Small, Jennifer L; Collins, Kathrine M; Tucker, Compton J; Pak, Edwin W; Britch, Seth C; Eastman, James Ronald; Pinzon, Jorge E; Russell, Kevin L

2012-01-01

Recent clusters of outbreaks of mosquito-borne diseases (Rift Valley fever and chikungunya) in Africa and parts of the Indian Ocean islands illustrate how interannual climate variability influences the changing risk patterns of disease outbreaks. Although Rift Valley fever outbreaks have been known to follow periods of above-normal rainfall, the timing of the outbreak events has largely been unknown. Similarly, there is inadequate knowledge on climate drivers of chikungunya outbreaks. We analyze a variety of climate and satellite-derived vegetation measurements to explain the coupling between patterns of climate variability and disease outbreaks of Rift Valley fever and chikungunya. We derived a teleconnections map by correlating long-term monthly global precipitation data with the NINO3.4 sea surface temperature (SST) anomaly index. This map identifies regional hot-spots where rainfall variability may have an influence on the ecology of vector borne disease. Among the regions are Eastern and Southern Africa where outbreaks of chikungunya and Rift Valley fever occurred 2004-2009. Chikungunya and Rift Valley fever case locations were mapped to corresponding climate data anomalies to understand associations between specific anomaly patterns in ecological and climate variables and disease outbreak patterns through space and time. From these maps we explored associations among Rift Valley fever disease occurrence locations and cumulative rainfall and vegetation index anomalies. We illustrated the time lag between the driving climate conditions and the timing of the first case of Rift Valley fever. Results showed that reported outbreaks of Rift Valley fever occurred after ∼3-4 months of sustained above-normal rainfall and associated green-up in vegetation, conditions ideal for Rift Valley fever mosquito vectors. For chikungunya we explored associations among surface air temperature, precipitation anomalies, and chikungunya outbreak locations. We found that chikungunya outbreaks occurred under conditions of anomalously high temperatures and drought over Eastern Africa. However, in Southeast Asia, chikungunya outbreaks were negatively correlated (p<0.05) with drought conditions, but positively correlated with warmer-than-normal temperatures and rainfall. Extremes in climate conditions forced by the El Niño/Southern Oscillation (ENSO) lead to severe droughts or floods, ideal ecological conditions for disease vectors to emerge, and may result in epizootics and epidemics of Rift Valley fever and chikungunya. However, the immune status of livestock (Rift Valley fever) and human (chikungunya) populations is a factor that is largely unknown but very likely plays a role in the spatial-temporal patterns of these disease outbreaks. As the frequency and severity of extremes in climate increase, the potential for globalization of vectors and disease is likely to accelerate. Understanding the underlying patterns of global and regional climate variability and their impacts on ecological drivers of vector-borne diseases is critical in long-range planning of appropriate disease and disease-vector response, control, and mitigation strategies.

International travellers from New Jersey: piloting a travel health module in the 2011 Behavioral Risk Factor Surveillance System survey†

PubMed Central

Stoney, Rhett J.; Kozarsky, Phyllis; Bostick, Roberd M.; Sotir, Mark J.

2016-01-01

Background In 2011, the Centers for Disease Control and Prevention and the New Jersey Department of Health used the New Jersey Behavioral Risk Factor Survey (NJBRFS), a state component of the national Behavioral Risk Factor Surveillance System (BRFSS) to pilot a travel health module designed to collect population-based data on New Jersey residents travelling internationally. Our objective was to use this population-based travel health information to serve as a baseline to evaluate trends in US international travellers. Methods A representative sample of New Jersey residents was identified through a random-digit-dialing method and administered the travel health module, which asked five questions: travel outside of USA during the previous year; destination; purpose; if a healthcare provider was visited before travel and any travel-related illness. Additional health variables from the larger NJBRFS were considered and included in bivariate analyses and multiple logistic regression; weights were assigned to variables to account for survey design complexity. Results Of 4029 participants, 841 (21%) travelled internationally. Top destinations included Mexico (10%), Canada (9%), Dominican Republic (6%), Bahamas (5%) and Italy (5%). Variables positively associated with travel included foreign birth, ≥$75 000 annual household income, college education and no children living in the household. One hundred fifty (18%) of 821 travellers with known destinations went to high-risk countries; 40% were visiting friends and relatives and only 30% sought pre-travel healthcare. Forty-eight (6%) of 837 responding travellers reported travel-related illness; 44% visited high-risk countries. Conclusions Approximately one in five NJBRFS respondents travelled internationally during the previous year, a sizeable proportion to high-risk destinations. Few reported becoming ill as a result of travel but almost one-half of those ill had travelled to high-risk destinations. Population-based surveillance data on travellers can help document trends in destinations, traveller type and disease prevalence and evaluate the effectiveness of disease prevention programmmes. PMID:26782130

Health Impacts of the Built Environment: Within-Urban Variability in Physical Inactivity, Air Pollution, and Ischemic Heart Disease Mortality

PubMed Central

Hankey, Steve; Brauer, Michael

2011-01-01

Background: Physical inactivity and exposure to air pollution are important risk factors for death and disease globally. The built environment may influence exposures to these risk factors in different ways and thus differentially affect the health of urban populations. Objective: We investigated the built environment’s association with air pollution and physical inactivity, and estimated attributable health risks. Methods: We used a regional travel survey to estimate within-urban variability in physical inactivity and home-based air pollution exposure [particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), nitrogen oxides (NOx), and ozone (O3)] for 30,007 individuals in southern California. We then estimated the resulting risk for ischemic heart disease (IHD) using literature-derived dose–response values. Using a cross-sectional approach, we compared estimated IHD mortality risks among neighborhoods based on “walkability” scores. Results: The proportion of physically active individuals was higher in high- versus low-walkability neighborhoods (24.9% vs. 12.5%); however, only a small proportion of the population was physically active, and between-neighborhood variability in estimated IHD mortality attributable to physical inactivity was modest (7 fewer IHD deaths/100,000/year in high- vs. low-walkability neighborhoods). Between-neighborhood differences in estimated IHD mortality from air pollution were comparable in magnitude (9 more IHD deaths/100,000/year for PM2.5 and 3 fewer IHD deaths for O3 in high- vs. low-walkability neighborhoods), suggesting that population health benefits from increased physical activity in high-walkability neighborhoods may be offset by adverse effects of air pollution exposure. Policy implications: Currently, planning efforts mainly focus on increasing physical activity through neighborhood design. Our results suggest that differences in population health impacts among neighborhoods are similar in magnitude for air pollution and physical activity. Thus, physical activity and exposure to air pollution are critical aspects of planning for cleaner, health-promoting cities. PMID:22004949

Health impacts of the built environment: within-urban variability in physical inactivity, air pollution, and ischemic heart disease mortality.

PubMed

Hankey, Steve; Marshall, Julian D; Brauer, Michael

2012-02-01

Physical inactivity and exposure to air pollution are important risk factors for death and disease globally. The built environment may influence exposures to these risk factors in different ways and thus differentially affect the health of urban populations. We investigated the built environment's association with air pollution and physical inactivity, and estimated attributable health risks. We used a regional travel survey to estimate within-urban variability in physical inactivity and home-based air pollution exposure [particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5), nitrogen oxides (NOx), and ozone (O3)] for 30,007 individuals in southern California. We then estimated the resulting risk for ischemic heart disease (IHD) using literature-derived dose-response values. Using a cross-sectional approach, we compared estimated IHD mortality risks among neighborhoods based on "walkability" scores. The proportion of physically active individuals was higher in high- versus low-walkability neighborhoods (24.9% vs. 12.5%); however, only a small proportion of the population was physically active, and between-neighborhood variability in estimated IHD mortality attributable to physical inactivity was modest (7 fewer IHD deaths/100,000/year in high- vs. low-walkability neighborhoods). Between-neighborhood differences in estimated IHD mortality from air pollution were comparable in magnitude (9 more IHD deaths/100,000/year for PM2.5 and 3 fewer IHD deaths for O3 in high- vs. low-walkability neighborhoods), suggesting that population health benefits from increased physical activity in high-walkability neighborhoods may be offset by adverse effects of air pollution exposure. Currently, planning efforts mainly focus on increasing physical activity through neighborhood design. Our results suggest that differences in population health impacts among neighborhoods are similar in magnitude for air pollution and physical activity. Thus, physical activity and exposure to air pollution are critical aspects of planning for cleaner, health-promoting cities.

Seasonal temperature variability and emergency hospital admissions for respiratory diseases: a population-based cohort study.

PubMed

Sun, Shengzhi; Laden, Francine; Hart, Jaime E; Qiu, Hong; Wang, Yan; Wong, Chit Ming; Lee, Ruby Siu-Yin; Tian, Linwei

2018-04-05

Climate change increases global mean temperature and changes short-term (eg, diurnal) and long-term (eg, intraseasonal) temperature variability. Numerous studies have shown that mean temperature and short-term temperature variability are both associated with increased respiratory morbidity or mortality. However, data on the impact of long-term temperature variability are sparse. We aimed to assess the association of intraseasonal temperature variability with respiratory disease hospitalisations among elders. We ascertained the first occurrence of emergency hospital admissions for respiratory diseases in a prospective Chinese elderly cohort of 66 820 older people (≥65 years) with 10-13 years of follow-up. We used an ordinary kriging method based on 22 weather monitoring stations in Hong Kong to spatially interpolate daily ambient temperature for each participant's residential address. Seasonal temperature variability was defined as the SD of daily mean summer (June-August) or winter (December-February) temperatures. We applied Cox proportional hazards regression with time-varying exposure of seasonal temperature variability to respiratory admissions. During the follow-up time, we ascertained 12 689 cases of incident respiratory diseases, of which 6672 were pneumonia and 3075 were COPD. The HRs per 1°C increase in wintertime temperature variability were 1.20 (95% CI 1.08 to 1.32), 1.15 (1.01 to 1.31) and 1.41 (1.15 to 1.71) for total respiratory diseases, pneumonia and COPD, respectively. The associations were not statistically significant for summertime temperature variability. Wintertime temperature variability was associated with higher risk of incident respiratory diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Gaps and perspectives of pathotype and race determination in golovinomyces cichoracearum and podosphaera xanthii.

USDA-ARS?s Scientific Manuscript database

Golovinomyces cichoracearum and Podosphaera xanthii (family Erysiphaceae) are the most important species causing cucurbit powdery mildew (CPM), a serious disease of field and greenhouse cucurbits. Both species are highly variable in their pathogenicity and virulence, as indicated by the existence of...

THREE-DIMENSIONAL COMPUTATIONAL FLUID DYNAMICS SIMULATIONS OF LOCAL PARTICLE DEPOSITION PATTERNS IN LUNG AIRWAYS

EPA Science Inventory

EPA has identified respirable particulate matter (PM) as a significant threat to human health, particularly in the elderly, in children, and in persons with respiratory disease. However, deposition of PM in the respiratory system is highly variable, depending upon particle chara...

The search for integrated management of common scab

USDA-ARS?s Scientific Manuscript database

Common scab (CS), caused by several species of Streptomyces, is a soil-borne bacterial disease of potato and other root and tuber crops. Frustratingly, CS severity is highly variable (and unpredictable) from year to year and location to location. Symptoms include superficial, raised, or pitted lesio...

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

PubMed Central

Sobral, Margarida; Paúl, Constança

2013-01-01

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

Diagnostic approach in leptospirosis patients

NASA Astrophysics Data System (ADS)

Sembiring, E.

2018-03-01

Leptospirosis is as a worldwide zoonotic disease, spread by pathogenic species of the bacterial genus Leptospira that occurs most commonly in tropical and subtropical regions which are one of endemic diseases in some places in Indonesia. The leptospira serovars are naturally carried in the renal tubules of rodents, wild and domestic animals. Human can be infected either through direct contact with urine of infected animals or indirect contact through with contaminated water and soil. Clinical manifestation is highly variable. The most cases are with a mild flu-like illness which may mimic many other diseases. Weil’s disease is the name given to severe illness and is characterized by a severe febrile illness with bleeding, jaundice and renal failure with high mortality rate. Leptospirosis has been frequently underdiagnosed and underreported. The diagnosis of leptospirosis is difficult to confirm and laboratory test is rarely available even in endemic areas.

Probabilistic modeling of anatomical variability using a low dimensional parameterization of diffeomorphisms.

PubMed

Zhang, Miaomiao; Wells, William M; Golland, Polina

2017-10-01

We present an efficient probabilistic model of anatomical variability in a linear space of initial velocities of diffeomorphic transformations and demonstrate its benefits in clinical studies of brain anatomy. To overcome the computational challenges of the high dimensional deformation-based descriptors, we develop a latent variable model for principal geodesic analysis (PGA) based on a low dimensional shape descriptor that effectively captures the intrinsic variability in a population. We define a novel shape prior that explicitly represents principal modes as a multivariate complex Gaussian distribution on the initial velocities in a bandlimited space. We demonstrate the performance of our model on a set of 3D brain MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Our model yields a more compact representation of group variation at substantially lower computational cost than the state-of-the-art method such as tangent space PCA (TPCA) and probabilistic principal geodesic analysis (PPGA) that operate in the high dimensional image space. Copyright © 2017 Elsevier B.V. All rights reserved.

IDENTIFYING GENETIC ASSOCIATIONS WITH VARIABILITY IN METABOLIC HEALTH AND BLOOD COUNT LABORATORY VALUES: DIVING INTO THE QUANTITATIVE TRAITS BY LEVERAGING LONGITUDINAL DATA FROM AN EHR.

PubMed

Verma, Shefali S; Lucas, Anastasia M; Lavage, Daniel R; Leader, Joseph B; Metpally, Raghu; Krishnamurthy, Sarathbabu; Dewey, Frederick; Borecki, Ingrid; Lopez, Alexander; Overton, John; Penn, John; Reid, Jeffrey; Pendergrass, Sarah A; Breitwieser, Gerda; Ritchie, Marylyn D

2017-01-01

A wide range of patient health data is recorded in Electronic Health Records (EHR). This data includes diagnosis, surgical procedures, clinical laboratory measurements, and medication information. Together this information reflects the patient's medical history. Many studies have efficiently used this data from the EHR to find associations that are clinically relevant, either by utilizing International Classification of Diseases, version 9 (ICD-9) codes or laboratory measurements, or by designing phenotype algorithms to extract case and control status with accuracy from the EHR. Here we developed a strategy to utilize longitudinal quantitative trait data from the EHR at Geisinger Health System focusing on outpatient metabolic and complete blood panel data as a starting point. Comprehensive Metabolic Panel (CMP) as well as Complete Blood Counts (CBC) are parts of routine care and provide a comprehensive picture from high level screening of patients' overall health and disease. We randomly split our data into two datasets to allow for discovery and replication. We first conducted a genome-wide association study (GWAS) with median values of 25 different clinical laboratory measurements to identify variants from Human Omni Express Exome beadchip data that are associated with these measurements. We identified 687 variants that associated and replicated with the tested clinical measurements at p<5×10-08. Since longitudinal data from the EHR provides a record of a patient's medical history, we utilized this information to further investigate the ICD-9 codes that might be associated with differences in variability of the measurements in the longitudinal dataset. We identified low and high variance patients by looking at changes within their individual longitudinal EHR laboratory results for each of the 25 clinical lab values (thus creating 50 groups - a high variance and a low variance for each lab variable). We then performed a PheWAS analysis with ICD-9 diagnosis codes, separately in the high variance group and the low variance group for each lab variable. We found 717 PheWAS associations that replicated at a p-value less than 0.001. Next, we evaluated the results of this study by comparing the association results between the high and low variance groups. For example, we found 39 SNPs (in multiple genes) associated with ICD-9 250.01 (Type-I diabetes) in patients with high variance of plasma glucose levels, but not in patients with low variance in plasma glucose levels. Another example is the association of 4 SNPs in UMOD with chronic kidney disease in patients with high variance for aspartate aminotransferase (discovery p-value: 8.71×10-09 and replication p-value: 2.03×10-06). In general, we see a pattern of many more statistically significant associations from patients with high variance in the quantitative lab variables, in comparison with the low variance group across all of the 25 laboratory measurements. This study is one of the first of its kind to utilize quantitative trait variance from longitudinal laboratory data to find associations among genetic variants and clinical phenotypes obtained from an EHR, integrating laboratory values and diagnosis codes to understand the genetic complexities of common diseases.

Contrast-Enhanced Ultrasound in the Diagnosis of Gallbladder Diseases: A Multi-Center Experience

PubMed Central

Liu, Lin-Na; Xu, Hui-Xiong; Lu, Ming-De; Xie, Xiao-Yan; Wang, Wen-Ping; Hu, Bing; Yan, Kun; Ding, Hong; Tang, Shao-Shan; Qian, Lin-Xue; Luo, Bao-Ming; Wen, Yan-Ling

2012-01-01

Objective To assess the usefulness of contrast–enhanced ultrasound (CEUS) in differentiating malignant from benign gallbladder (GB) diseases. Methods This study had institutional review board approval. 192 patients with GB diseases from 9 university hospitals were studied. After intravenous bonus injection of a phospholipid-stabilized shell microbubble contrast agent, lesions were scanned with low acoustic power CEUS. A multiple logistic regression analysis was performed to identify diagnostic clues from 17 independent variables that enabled differentiation between malignant and benign GB diseases. Receiver operating characteristic (ROC) curve analysis was performed. Results Among the 17 independent variables, multiple logistic regression analysis showed that the following 4 independent variables were associated with the benign nature of the GB diseases, including the patient age, intralesional blood vessel depicted on CEUS, contrast washout time, and wall intactness depicted on CEUS (all P<0.05). ROC analysis showed that the patient age, intralesional vessels on CEUS, and the intactness of the GB wall depicted on CEUS yielded an area under the ROC curve (Az) greater than 0.8 in each and Az for the combination of the 4 significant independent variables was 0.915 [95% confidence interval (CI): 0.857–0.974]. The corresponding Az, sensitivity, and specificity for the age were 0.805 (95% CI: 0.746–0.863), 92.2%%, and 59.6%; for the intralesional vessels on CEUS were 0.813 (95% CI: 0.751–0.875), 59.8%, and 98.0%; and for the GB wall intactness were 0.857 (95% CI: 0.786–0.928), 78.4%, and 92.9%. The cut-off values for benign GB diseases were patient age <53.5 yrs, dotted intralesional vessels on CEUS and intact GB wall on CEUS. Conclusion CEUS is valuable in differentiating malignant from benign GB diseases. Branched or linear intralesional vessels and destruction of GB wall on CEUS are the CEUS features highly suggestive of GB malignancy and the patient age >53.5 yrs is also a clue for GB malignancy. PMID:23118996

Gender Differences in Autonomic Control of the Cardiovascular System.

PubMed

Pothineni, Naga Venkata; Shirazi, Lily F; Mehta, Jawahar L

2016-01-01

The autonomic nervous system (ANS) is a key regulator of the cardiovascular system. The two arms of the ANS, sympathetic and parasympathetic (vagal) have co-regulatory effects on cardiac homeostasis. ANS modulation and dysfunction are also believed to affect various cardiac disease states. Over the past decade, there has been increasing evidence suggesting gender differences in ANS activity. In multiple previous studies, ANS activity was primarily assessed using heart rate variability, muscle sympathetic nerve activity, coronary blood flow velocity, and plasma biomarkers. Heart rate variability is a non-invasive measure, which can be analyzed in terms of low frequency and high frequency oscillations, which indicate the sympathetic and parasympathetic tone, respectively. These measures have been studied between women and men in states of rest and stress, and in cardiac disease. Studies support the concept of a significant gender difference in ANS activity. Further studies are indicated to elucidate specific differences and mechanisms, which could guide targeted therapy of various cardiovascular disease states.

The genetics of aniridia - simple things become complicated.

PubMed

Wawrocka, Anna; Krawczynski, Maciej R

2018-05-01

Aniridia is a rare, panocular disorder characterized by a variable degree of hypoplasia or the absence of iris tissue associated with additional ocular abnormalities. It is inherited in an autosomal dominant manner, with high penetrance and variable expression even within the same family. In most cases the disease is caused by haploinsufficiency truncating mutations in the PAX6 gene; however, in up to 30% of aniridia patients, disease results from chromosomal rearrangements at the 11p13 region. The aim of this review is to present the clinical and genetic aspects of the disease. Furthermore, we present a molecular diagnostic strategy in the aniridia patients. Recent improvement in the genetic diagnostic approach will precisely diagnosis aniridia patients, which is essential especially for children with aniridia in order to determine the risk of developing a Wilms tumor or neurodevelopmental disorder. Finally, based on the previous studies we describe the current knowledge and latest research findings in the topic of pathogenesis of aniridia and possible future treatment.

Quantifying the influence of temperature on hand, foot and mouth disease incidence in Wuhan, Central China.

PubMed

Huang, Jiao; Chen, Shi; Wu, Yang; Tong, Yeqing; Wang, Lei; Zhu, Min; Hu, Shuhua; Guan, Xuhua; Wei, Sheng

2018-01-31

Hand, foot and mouth disease (HFMD) is a substantial burden throughout Asia, but the effects of temperature pattern on HFMD risk are inconsistent. To quantify the effect of temperature on HFMD incidence, Wuhan was chosen as the study site because of its high temperature variability and high HFMD incidence. Daily series of HFMD counts and meteorological variables during 2010-2015 were obtained. Distributed lag non-linear models were applied to characterize the temperature-HFMD relationship and to assess its variability across different ages, genders, and types of child care. Totally, 80,219 patients of 0-5 years experienced HFMD in 2010-2015 in Wuhan. The cumulative relative risk of HFMD increased linearly with temperature over 7 days (lag0-7), while it presented as an approximately inverted V-shape over 14 days (lag0-14). The cumulative relative risk at lag0-14 peaked at 26.4 °C with value of 2.78 (95%CI: 2.08-3.72) compared with the 5 th percentile temperature (1.7 °C). Subgroup analyses revealed that children attended daycare were more vulnerable to temperature variation than those cared for at home. This study suggests that public health actions should take into consideration local weather conditions and demographic characteristics.

Partial Least Squares for Discrimination in fMRI Data

PubMed Central

Andersen, Anders H.; Rayens, William S.; Liu, Yushu; Smith, Charles D.

2011-01-01

Multivariate methods for discrimination were used in the comparison of brain activation patterns between groups of cognitively normal women who are at either high or low Alzheimer's disease risk based on family history and apolipoprotein-E4 status. Linear discriminant analysis (LDA) was preceded by dimension reduction using either principal component analysis (PCA), partial least squares (PLS), or a new oriented partial least squares (OrPLS) method. The aim was to identify a spatial pattern of functionally connected brain regions that was differentially expressed by the risk groups and yielded optimal classification accuracy. Multivariate dimension reduction is required prior to LDA when the data contains more feature variables than there are observations on individual subjects. Whereas PCA has been commonly used to identify covariance patterns in neuroimaging data, this approach only identifies gross variability and is not capable of distinguishing among-groups from within-groups variability. PLS and OrPLS provide a more focused dimension reduction by incorporating information on class structure and therefore lead to more parsimonious models for discrimination. Performance was evaluated in terms of the cross-validated misclassification rates. The results support the potential of using fMRI as an imaging biomarker or diagnostic tool to discriminate individuals with disease or high risk. PMID:22227352

Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease

NASA Technical Reports Server (NTRS)

Hausdorff, J. M.; Cudkowicz, M. E.; Firtion, R.; Wei, J. Y.; Goldberger, A. L.

1998-01-01

The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three times that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects, HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings.

[Prevalence and factors associated with peripheral artery disease in patients with type 2 diabetes mellitus in Primary Care].

PubMed

Montero-Monterroso, J L; Gascón-Jiménez, J A; Vargas-Rubio, M D; Quero-Salado, C; Villalba-Marín, P; Pérula-de Torres, L A

2015-01-01

Peripheral artery disease in the lower limbs (PAD) is a prevalent condition that entails high morbidity in diabetic patients; this study assesses PAD in these patients and its socio-demographic and clinic associated variables. Descriptive study in a systematic sample of diabetic patients (DM2) aged 50-80 years, in Primary Care settings. The dependent variable was the presence of PAD diagnosed by ankle-brachial index (ABI) ≤ 0.9; independent variables: socio-demographic, clinical and laboratory. bivariate and multiple logistic regression analyses were performed to determine the variables associated with low ABI. A sample of 251 patients, 52.6% women; mean age: 68.5 ±8.5. A low ABI was detected in 18.3% (95% Confidence Interval (95% CI):13.3-23.3%), with 6 subjets (2.4%) previously diagnosed as suffering PAD. Age (OR=1.07; 95% CI: 1.02-1.12) and retinopathy (OR=2.69; 95% CI: 1.06-6.81) were associated (multiple logistic regression analysis) with ABI. The percentage of patients diagnosed with PAD is very low, although PAD prevalence is high among DM2 patients attending Primary Care clinics, especially in older patients and those with retinopathy. We emphasize the recommendation of performing the ABI test in this population at risk. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

A Bayesian Framework for Generalized Linear Mixed Modeling Identifies New Candidate Loci for Late-Onset Alzheimer’s Disease

PubMed Central

Wang, Xulong; Philip, Vivek M.; Ananda, Guruprasad; White, Charles C.; Malhotra, Ankit; Michalski, Paul J.; Karuturi, Krishna R. Murthy; Chintalapudi, Sumana R.; Acklin, Casey; Sasner, Michael; Bennett, David A.; De Jager, Philip L.; Howell, Gareth R.; Carter, Gregory W.

2018-01-01

Recent technical and methodological advances have greatly enhanced genome-wide association studies (GWAS). The advent of low-cost, whole-genome sequencing facilitates high-resolution variant identification, and the development of linear mixed models (LMM) allows improved identification of putatively causal variants. While essential for correcting false positive associations due to sample relatedness and population stratification, LMMs have commonly been restricted to quantitative variables. However, phenotypic traits in association studies are often categorical, coded as binary case-control or ordered variables describing disease stages. To address these issues, we have devised a method for genomic association studies that implements a generalized LMM (GLMM) in a Bayesian framework, called Bayes-GLMM. Bayes-GLMM has four major features: (1) support of categorical, binary, and quantitative variables; (2) cohesive integration of previous GWAS results for related traits; (3) correction for sample relatedness by mixed modeling; and (4) model estimation by both Markov chain Monte Carlo sampling and maximal likelihood estimation. We applied Bayes-GLMM to the whole-genome sequencing cohort of the Alzheimer’s Disease Sequencing Project. This study contains 570 individuals from 111 families, each with Alzheimer’s disease diagnosed at one of four confidence levels. Using Bayes-GLMM we identified four variants in three loci significantly associated with Alzheimer’s disease. Two variants, rs140233081 and rs149372995, lie between PRKAR1B and PDGFA. The coded proteins are localized to the glial-vascular unit, and PDGFA transcript levels are associated with Alzheimer’s disease-related neuropathology. In summary, this work provides implementation of a flexible, generalized mixed-model approach in a Bayesian framework for association studies. PMID:29507048

Mitochondrial DNA Genetics and the Heteroplasmy Conundrum in Evolution and Disease

PubMed Central

Wallace, Douglas C.; Chalkia, Dimitra

2013-01-01

The unorthodox genetics of the mtDNA is providing new perspectives on the etiology of the common “complex” diseases. The maternally inherited mtDNA codes for essential energy genes, is present in thousands of copies per cell, and has a very high mutation rate. New mtDNA mutations arise among thousands of other mtDNAs. The mechanisms by which these “heteroplasmic” mtDNA mutations come to predominate in the female germline and somatic tissues is poorly understood, but essential for understanding the clinical variability of a range of diseases. Maternal inheritance and heteroplasmy also pose major challengers for the diagnosis and prevention of mtDNA disease. PMID:24186072

Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

PubMed

Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

2014-04-10

In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Body Fat Percentage Prediction Using Intelligent Hybrid Approaches

PubMed Central

Shao, Yuehjen E.

2014-01-01

Excess of body fat often leads to obesity. Obesity is typically associated with serious medical diseases, such as cancer, heart disease, and diabetes. Accordingly, knowing the body fat is an extremely important issue since it affects everyone's health. Although there are several ways to measure the body fat percentage (BFP), the accurate methods are often associated with hassle and/or high costs. Traditional single-stage approaches may use certain body measurements or explanatory variables to predict the BFP. Diverging from existing approaches, this study proposes new intelligent hybrid approaches to obtain fewer explanatory variables, and the proposed forecasting models are able to effectively predict the BFP. The proposed hybrid models consist of multiple regression (MR), artificial neural network (ANN), multivariate adaptive regression splines (MARS), and support vector regression (SVR) techniques. The first stage of the modeling includes the use of MR and MARS to obtain fewer but more important sets of explanatory variables. In the second stage, the remaining important variables are served as inputs for the other forecasting methods. A real dataset was used to demonstrate the development of the proposed hybrid models. The prediction results revealed that the proposed hybrid schemes outperformed the typical, single-stage forecasting models. PMID:24723804

Excised leaf method for high volume evaluation of sorghum germplasm for resistance against Colletotrichum sublineolum

USDA-ARS?s Scientific Manuscript database

Foliar phase of anthracnose, caused by Colletotrichum sublineolum is the most important leaf disease of sorghum. Due to the hyper-variable nature of the fungus, continuous evaluation of sorghum germplasm to identify new sources of resistance is imperative. Field and greenhouse evaluations for anth...

Evaluating variable rate fungicide applications for control of Sclerotinia

USDA-ARS?s Scientific Manuscript database

Oklahoma peanut growers continue to try to increase yields and reduce input costs. Perhaps the largest input in a peanut crop is fungicide applications. This is especially true for areas in the state that have high disease pressure from Sclerotinia. On average, a single fungicide application cost...

Chlorate poisoning in beef cattle

PubMed Central

Blakley, Barry R.; Fraser, Lorrie M.; Waldner, Cheryl

2007-01-01

A disease syndrome characterized by hemolysis, methemoglobinemia, methemoglobinuria, and death was observed in a herd of purebred Limousin beef cattle grazing on pasture in November in Alberta. Improper disposal of the nonselective herbicide, sodium chlorate, was identified as the causal agent. Highly variable blood methemoglobin levels reflected differences in herbicide consumption. PMID:17987970

Will all the trees fall? Variable resistance to an introduced forest disease in a highly susceptible host

Treesearch

K.J. Hayden; A. Nettel; R.S. Dodd; M. Garbelotto

2011-01-01

Although tanoak (Notholithocarpus densiflorus syn. Lithocarpus densiflorus) is the species most affected by the introduced pathogen Phytophthora ramorum, with demonstrable risk of extirpation, little is known about the origin, range or structuring of the tree's susceptibility. We examined variation in...

Understanding the molecular basis of the resistance of Phytophthora infestans to fungicides by functional genomics

USDA-ARS?s Scientific Manuscript database

Development of resistance to fungicides is a major concern in managing potato late blight disease caused by Phytophthora infestans. The problem is P. infestans is capable of sexual recombination contributing to increased strain variability and high adaptability that hastens the development of resis...

Variability associated with screening for common scab and verticillium wilt in potato

USDA-ARS?s Scientific Manuscript database

Common Scab (CS) and Verticillium Wilt (VW) are caused by the soilborne bacteria Streptomyces scabies, and fungi, Verticillium dahliae and V. albo-atrum, respectively, in potato (Solanum tuberosum). Both diseases result in biological and/or marketable yield loss and are tested in fields with high di...

Phylogeny and variability of Colletotrichum truncatum associated with soybean anthracnose in Brazil.

PubMed

Rogério, F; Ciampi-Guillardi, M; Barbieri, M C G; Bragança, C A D; Seixas, C D S; Almeida, A M R; Massola, N S

2017-02-01

Fungal diseases are among the main factors limiting high yields of soybean crop. Colletotrichum isolates from soybean plants with anthracnose symptoms were studied from different regions and time periods in Brazil using molecular, morphological and pathogenic analyses. Bayesian phylogenetic inference of GAPDH, HIS3 and ITS-5.8S rDNA sequences, the morphologies of colony and conidia, and inoculation tests on seeds and seedlings were performed. All isolates clustered only with Colletotrichum truncatum species in three well-separated clusters. Intraspecific genetic diversity revealed 27 distinct haplotypes in 51 fungal isolates; some of which were identical to C. truncatum sequences from other regions around the world, while others were related to alternative hosts. Conidia were falcate, hyaline, unicellular and aseptate, formed in acervuli, with variable dimensions. Despite being pathogenic to seedlings by both inoculation methods, variation was observed in the aggressiveness of the tested isolates, which was not correlated with genetic variation. The identification of C. truncatum in the sampled isolates was evidenced as being the only causal agent of soybean anthracnose in Brazil until 2007, with relevant genetic, morphological and pathogenic variability as well as a broad geographical origin. The wide distribution of the predominant C. truncatum haplotype indicated the existence of a highly efficient mechanism of pathogen dispersal over long distances, reinforcing the role of seeds as the primary source of disease inoculum. The characterization and distribution of Colletotrichum species in soybean-producing regions in Brazil is fundamental for understanding the disease epidemiology and for ensuring effective control strategies against anthracnose. © 2016 The Society for Applied Microbiology.

Mathematical biomarkers for the autonomic regulation of cardiovascular system.

PubMed

Campos, Luciana A; Pereira, Valter L; Muralikrishna, Amita; Albarwani, Sulayma; Brás, Susana; Gouveia, Sónia

2013-10-07

Heart rate and blood pressure are the most important vital signs in diagnosing disease. Both heart rate and blood pressure are characterized by a high degree of short term variability from moment to moment, medium term over the normal day and night as well as in the very long term over months to years. The study of new mathematical algorithms to evaluate the variability of these cardiovascular parameters has a high potential in the development of new methods for early detection of cardiovascular disease, to establish differential diagnosis with possible therapeutic consequences. The autonomic nervous system is a major player in the general adaptive reaction to stress and disease. The quantitative prediction of the autonomic interactions in multiple control loops pathways of cardiovascular system is directly applicable to clinical situations. Exploration of new multimodal analytical techniques for the variability of cardiovascular system may detect new approaches for deterministic parameter identification. A multimodal analysis of cardiovascular signals can be studied by evaluating their amplitudes, phases, time domain patterns, and sensitivity to imposed stimuli, i.e., drugs blocking the autonomic system. The causal effects, gains, and dynamic relationships may be studied through dynamical fuzzy logic models, such as the discrete-time model and discrete-event model. We expect an increase in accuracy of modeling and a better estimation of the heart rate and blood pressure time series, which could be of benefit for intelligent patient monitoring. We foresee that identifying quantitative mathematical biomarkers for autonomic nervous system will allow individual therapy adjustments to aim at the most favorable sympathetic-parasympathetic balance.

Mathematical biomarkers for the autonomic regulation of cardiovascular system

PubMed Central

Campos, Luciana A.; Pereira, Valter L.; Muralikrishna, Amita; Albarwani, Sulayma; Brás, Susana; Gouveia, Sónia

2013-01-01

Heart rate and blood pressure are the most important vital signs in diagnosing disease. Both heart rate and blood pressure are characterized by a high degree of short term variability from moment to moment, medium term over the normal day and night as well as in the very long term over months to years. The study of new mathematical algorithms to evaluate the variability of these cardiovascular parameters has a high potential in the development of new methods for early detection of cardiovascular disease, to establish differential diagnosis with possible therapeutic consequences. The autonomic nervous system is a major player in the general adaptive reaction to stress and disease. The quantitative prediction of the autonomic interactions in multiple control loops pathways of cardiovascular system is directly applicable to clinical situations. Exploration of new multimodal analytical techniques for the variability of cardiovascular system may detect new approaches for deterministic parameter identification. A multimodal analysis of cardiovascular signals can be studied by evaluating their amplitudes, phases, time domain patterns, and sensitivity to imposed stimuli, i.e., drugs blocking the autonomic system. The causal effects, gains, and dynamic relationships may be studied through dynamical fuzzy logic models, such as the discrete-time model and discrete-event model. We expect an increase in accuracy of modeling and a better estimation of the heart rate and blood pressure time series, which could be of benefit for intelligent patient monitoring. We foresee that identifying quantitative mathematical biomarkers for autonomic nervous system will allow individual therapy adjustments to aim at the most favorable sympathetic-parasympathetic balance. PMID:24109456

Big data and computational biology strategy for personalized prognosis.

PubMed

Ow, Ghim Siong; Tang, Zhiqun; Kuznetsov, Vladimir A

2016-06-28

The era of big data and precision medicine has led to accumulation of massive datasets of gene expression data and clinical information of patients. For a new patient, we propose that identification of a highly similar reference patient from an existing patient database via similarity matching of both clinical and expression data could be useful for predicting the prognostic risk or therapeutic efficacy.Here, we propose a novel methodology to predict disease/treatment outcome via analysis of the similarity between any pair of patients who are each characterized by a certain set of pre-defined biological variables (biomarkers or clinical features) represented initially as a prognostic binary variable vector (PBVV) and subsequently transformed to a prognostic signature vector (PSV). Our analyses revealed that Euclidean distance rather correlation distance measure was effective in defining an unbiased similarity measure calculated between two PSVs.We implemented our methods to high-grade serous ovarian cancer (HGSC) based on a 36-mRNA predictor that was previously shown to stratify patients into 3 distinct prognostic subgroups. We studied and revealed that patient's age, when converted into binary variable, was positively correlated with the overall risk of succumbing to the disease. When applied to an independent testing dataset, the inclusion of age into the molecular predictor provided more robust personalized prognosis of overall survival correlated with the therapeutic response of HGSC and provided benefit for treatment targeting of the tumors in HGSC patients.Finally, our method can be generalized and implemented in many other diseases to accurately predict personalized patients' outcomes.

Self-perception and oral health in pregnant adolescents.

PubMed

Rovida, T A Saliba; Moimaz, S A Saliba; Lima, D P; Garbin, C A Saliba

2014-09-01

To evaluate the oral health indicators by determining the experience of dental caries and periodontal disease and identification of self-perceived oral health status of pregnant adolescents and to assess the association between the studied variables. A transversal study, survey type and survey of the oral health status of 127 adolescents, 10-19 years of age, pregnant, accompanied by the Unified Health System of Araçatuba-SP was performed. The self-perceived oral health and socio-demographic data were recorded using an adapted questionnaire. The oral health statuses were analyzed using the DMFT and CPI indices in accordance with the criteria established by the WHO for epidemiological survey. Descriptive statistical analyzes and the Fisher's exact test with a significance level of 5% was performed, as well as a logistic regression analysis to verify the association between the variables. Of the total, 41.0% reported having satisfactory oral health, while 63.0% believed they had problems with their teeth and gums. The DMFT index was 12.51 (SD = 4.21). The percentage of caries-free was 6.3%, and 91.3% had periodontal problems. A statistically significant association was found between the variables: self-perceived oral health and periodontal disease p = 0.0166 and self-reported gum disease and periodontal disease p = 0.0039. Most patients considered their oral health as poor and reported having dental and gum problems, which can also be observed in the clinical examination since the caries experience of the pregnant women examined was considered high and the symptoms of periodontal disease were observed in most of the volunteers.

Personality and reported quality of life in Parkinson's disease.

PubMed

Pontone, Gregory M; Mari, Zoltan; Perepezko, Kate; Weiss, Howard D; Bassett, Susan S

2017-03-01

Personality affects an individual's ability to cope with the burden of chronic disease. However, the impact of personality on quality of life (QoL) in Parkinson's disease (PD) is not well characterized. The goal of this study is to determine the effect of personality on QoL in PD. The study included 92 patients with idiopathic PD from Baltimore-Washington area movement disorder neurology clinics. QoL was assessed using the 37-item Parkinson's disease Quality of Life Questionnaire (PDQL) total score, and the Neuroticism-Extraversion-Openness Inventory was used to determine personality traits. Step-wise regression models examined the contribution of personality, depression, demographic, and PD variables on PDQL-assessed QoL. Neuroticism, conscientiousness, years of education, and depression explained 42% of the variance in the PDQL total score after adjusting for other disease variables. High neuroticism (β = -0.727, 95% confidence interval (CI) -1.125, -0.328, p < 0.0001) and depression (β = -9.058, 95%CI -17.46, -0.657, p = 0.035) negatively affected the PDQL, while high conscientiousness (β = 0.468, 95%CI 0.078, 0.858, p = 0.019), and years of education (β = 1.441, 95%CI 0.371, 2.510, p = 0.009) were positive factors. Personality can have a positive or negative influence on QoL in PD. PD patients with otherwise similar disease burdens and depressive symptoms may experience different levels of QoL depending on the level of neurotic or conscientious personality traits. Therefore, when interpreting patient responses on the PDQL, it is important to understand whether they reflect aspects of PD, that is, motor impairment and depression, which are amenable to treatment or whether they reflect personality traits. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of anatomic and morphologic nomogram to predict malignant and high-grade disease in a cohort of patients with small renal masses.

PubMed

Bagrodia, Aditya; Harrow, Brian; Liu, Zhuo-Wei; Olweny, Ephrem O; Faddegon, Stephen; Yin, Gang; Tan, Yung Khan; Han, Woong Kyu; Lotan, Yair; Margulis, Vitaly; Cadeddu, Jeffrey A

2014-01-01

To evaluate a nomogram using the RENAL Nephrometry Score (RENAL-NS) that was developed to characterize masses as benign vs. malignant and high vs. low grade in our patients with small renal masses treated with partial nephrectomy (PN). The nomogram was previously developed and validated in patients with widely variable tumor sizes. Retrospective review of PN performed between 1/2003 and 7/2011. Imaging was reviewed by a urologic surgeon for RENAL-NS. Final pathology was used to classify tumors as benign or malignant and low (I/II) or high (III/IV) Fuhrman grade. Patient age, gender, and RENAL score were entered into the nomogram described by Kutikov et al. to determine probabilities of cancer and high-grade disease. Area under the curve was determined to assess agreement between observed and expected outcomes for prediction of benign vs. malignant disease and for prediction of high- vs. low-grade or benign disease. A total of 250 patients with 252 masses underwent PN during the study period; 179/250 (71.6%) had preoperative imaging available. RENAL-NS was assigned to 181 masses. Twenty-two percent of tumors were benign. Eighteen percent of tumors were high grade. Area under the curve was 0.648 for predicting benign vs. malignant disease and 0.955 for predicting low-grade or benign vs. high-grade disease. The RENAL-NS score nomogram by Kutikov does not discriminate well between benign and malignant disease for small renal masses. The nomogram may potentially be useful in identifying high-grade tumors. Further validation is required where the nomogram probability and final pathologic specimen are available. Copyright © 2014 Elsevier Inc. All rights reserved.

VISIT-TO-VISIT VARIABILITY OF BLOOD PRESSURE AND DEATH, ESRD AND CARDIOVASCULAR EVENTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

PubMed Central

CHANG, Tara I.; TABADA, Grace H.; YANG, Jingrong; TAN, Thida X.; GO, Alan S.

2016-01-01

OBJECTIVES Visit-to-visit variability of blood pressure is an important independent risk factor for premature death and cardiovascular events, but relatively little is known about this phenomenon in patients with chronic kidney disease not yet on dialysis. METHODS We conducted a retrospective study in a community-based cohort of 114,900 adults with chronic kidney disease stages 3–4 (estimated glomerular filtration rate 15–59 mL/min per 1.73 m2). We hypothesized that visit-to-visit variability of blood pressure would be independently associated with higher risks of death, incident treated end-stage renal disease, and cardiovascular events. We defined systolic visit-to-visit variability of blood pressure using three metrics: (1) coefficient of variation (2) standard deviation of the mean systolic blood pressure, and (3) average real variability. RESULTS The highest versus the lowest quintile of the coefficient of variation was associated with higher adjusted rates of death (hazard ratio 1.22; 95% confidence interval 1.11–1.34) and hemorrhagic stroke (hazard ratio 1.91, confidence interval 1.36–2.68). Visit-to-visit variability of blood pressure was inconsistently associated with heart failure, and was not significantly associated with acute coronary syndrome and ischemic stroke. Results were similar when using the other two visit-to-visit variability of blood pressure. Visit-to-visit variability of blood pressure had inconsistent associations with end-stage renal disease, perhaps due to the relatively low incidences of this outcome. CONCLUSIONS Higher visit-to-visit variability of blood pressure is independently associated with higher rates of death and hemorrhagic stroke in patients with moderate to advanced chronic kidney disease not yet on dialysis. PMID:26599220

Early evolution of HLA-associated escape mutations in variable Gag proteins predicts CD4+ decline in HIV-1 subtype C infected women

PubMed Central

Chopera, Denis R.; Ntale, Roman; Ndabambi, Nonkululeko; Garrett, Nigel; Gray, Clive M.; Matten, David; Karim, Quarraisha Abdool; Karim, Salim Abdool; Williamson, Carolyn

2016-01-01

Objective HIV-1 escape from cytotoxic T-lymphocytes (CTL) results in the accumulation of HLA-associated mutations in the viral genome. To understand the contribution of early escape to disease progression, this study investigated the evolution and pathogenic implications of CTL escape in a cohort followed from infection for five years. Methods Viral loads and CD4+ counts were monitored in 78 subtype C infected individuals from onset of infection until CD4+ decline to <350 cells/μl or five years post-infection. The gag gene was sequenced and HLA-associated changes between enrolment and 12 months post-infection were mapped. Results HLA-associated escape mutations were identified in 48 (62%) of the participants and were associated with CD4+ decline to <350 copies/ml (p=0.05). Escape mutations in variable Gag proteins (p17 and p7p6) had a greater impact on disease progression than escape in more conserved regions (p24) (p=0.03). The association between HLA-associated escape mutations and CD4+ decline was independent of protective HLA allele (B*57, B*58:01, B*81) expression. Conclusion The high frequency of escape contributed to rapid disease progression in this cohort. While HLA-adaption in both conserved and variable Gag domains in the first year of infection was detrimental to long term clinical outcome, escape in variable domains had greater impact. PMID:27755110

Impact of Pharmacotherapy on Quality of Life in Patients with Parkinson's Disease.

PubMed

Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Forjaz, Maria João; Kurtis, Monica M

2015-05-01

Quality of life (QoL) is a patient-reported outcome frequently included in Parkinson's disease (PD) clinical trials as a secondary or tertiary endpoint. However, QoL is an important variable that reflects the impact of disease and treatment from the patients' perspective. In a chronic, neurodegenerative disease such as PD, with a wide range of complex symptoms, QoL provides valuable and comprehensive information on the patients' health status. This narrative review aims to evaluate the effect of specific PD treatments currently in use on patients' QoL measured with the Parkinson's Disease Questionnaire, 39-item (PDQ-39) or 8-item (PDQ-8) version. A quantification of this effect is provided by calculation of the relative change and effect size. These two parameters allow an intuitive standardized approach to the importance of change based on its magnitude. Some high-quality studies (Level I) were found for levodopa (immediate- or extended-release formulations), levodopa with added-on catechol-O-methyltransferase (COMT) inhibitors, levodopa/carbidopa gel for intestinal infusion, some dopamine agonists (ropinirole, cabergoline, pergolide), and the monoamine oxidase B (MAO-B) inhibitor safinamide. As a whole, these studies found a beneficial effect of variable magnitude, weak to moderate, on patients' QoL. Studies with a lower level of evidence or not providing enough data to estimate relative change and effect size, including those for the apomorphine subcutaneous pump, also reported improvement of QoL, but the evidence was insufficient to confirm the effect. More high-quality studies focused on QoL are needed to determine the real impact of PD drug treatments for this important outcome.

Highly conserved CDR3 region in circulating CD4+Vβ5+ T cells may be associated with cytotoxic activity in Chagas disease

PubMed Central

Menezes, C A S; Sullivan, A K; Falta, M T; Mack, D G; Freed, B M; Rocha, M O C; Gollob, K J; Fontenot, A P; Dutra, W O

2012-01-01

Human infection with Trypanosoma cruzi leads to Chagas disease, which presents as several different clinical conditions ranging from an asymptomatic form to a severe dilated cardiomyopathy. Several studies have demonstrated that T cells play a critical role in the development of cardiac pathology, as well as in immunoregulation during chronic disease. However, the mechanisms that drive protective or pathogenic T cell response are not known. We have shown that CD4+ T cells from chagasic patients preferentially express T cell receptor (TCR) β-chain variable region (Vβ) 5. The aim of this work was to determine whether T cells expressing this particular Vβ region displayed variable or restricted CDR3 sequences, as an indicator of the nature of the stimulus leading to the activation of these T cells in vivo. Additionally, we aimed to evaluate phenotypic characteristics of these cells that might be associated with pathology. CDR3 junctional region sequencing of Vβ5·1 expressing CD4+ T cells revealed the occurrence of a highly homologous CDR3 region with conserved TCR Jβ region usage among patients with cardiac, but not indeterminate, Chagas disease. Moreover, correlation analysis indicated that the frequency of CD4+Vβ5·1+ cells is associated with granzyme A expression, suggesting that these cells might display cytotoxic function. Together these results provide new insight into T cell recognition of antigens involved in Chagas disease and suggest that these cells may be implicated in the pathogenesis of chagasic cardiomyopathy. PMID:22774985

A new spiral dental implant: a tool for oral rehabilitation of difficult cases

PubMed Central

BALAN, I.; CALCATERRA, R.; LAURITANO, D.; GRECCHI, E.; CARINCI, F.

2017-01-01

SUMMARY Spiral dental implant (SDI) is an implant with a conical internal helix that confers the characteristic of self-drilling, self-tapping, and self-bone condensing. These proprieties offer better control during insertion of SDI giving a high primary stabilization, even in poor quality bone. A shorter diameter of SDI results in reduced drilling during insertion and consequently less trauma and minimal bone loss. To address the research purpose, the investigators designed a retrospective cohort study. The study population was composed of 25 patients, 11 males and 14 females that have been treated by Dr. Balan with 187 SDI positioned in mandible and into maxilla bone. The implants were placed during the years 2013 to 2014 in Dr. Balan clinic. All patients underwent the same surgical protocol. Several variables are investigated: demographic (age and gender), anatomic (upper/lower jaws and tooth site), implant (length and diameter and type) variables, edentulism (partial or total), and comorbid status of health (i.e.: hypothyroidism, parodontitis, hypertension, diabetes, presence of cancer, heart disease, hepatitis and rheumatologic disease). Pearson Chi-Square test was used to investigate variables and p < 0.05 was considered statistically significant. Statistically it has been shown that females have a higher possibility of unsuccessful respect of male, with a “p value” of 0.014. Another important impact factor for success of implant insertion has been represented by concomitants pathologies: cancer represents the most negative high factor risk with a percentage of unsuccessful of 50%, followed by heart disease (15%), and diabetes (3.7%). SDIs are reliable tools for difficult cases of oral rehabilitation. They have a higher success and survival rate, which means stable results over time. No differences were detected among SDI lengths, implant/crown ratio. In addition, the insertion of SDIs in banked bone can be performed without adverse effects. Finally, flapless and computer tomography-planned surgery does not significantly increase the clinical outcome of SDIs in complex rehabilitation. Cancer represents the most important variable to consider when a patient wants to do oral rehabilitation because of its high risk of unsuccessful. PMID:29285328

A new spiral dental implant: a tool for oral rehabilitation of difficult cases.

PubMed

Balan, I; Calcaterra, R; Lauritano, D; Grecchi, E; Carinci, F

2017-01-01

Spiral dental implant (SDI) is an implant with a conical internal helix that confers the characteristic of self-drilling, self-tapping, and self-bone condensing. These proprieties offer better control during insertion of SDI giving a high primary stabilization, even in poor quality bone. A shorter diameter of SDI results in reduced drilling during insertion and consequently less trauma and minimal bone loss. To address the research purpose, the investigators designed a retrospective cohort study. The study population was composed of 25 patients, 11 males and 14 females that have been treated by Dr. Balan with 187 SDI positioned in mandible and into maxilla bone. The implants were placed during the years 2013 to 2014 in Dr. Balan clinic. All patients underwent the same surgical protocol. Several variables are investigated: demographic (age and gender), anatomic (upper/lower jaws and tooth site), implant (length and diameter and type) variables, edentulism (partial or total), and comorbid status of health (i.e.: hypothyroidism, parodontitis, hypertension, diabetes, presence of cancer, heart disease, hepatitis and rheumatologic disease). Pearson Chi-Square test was used to investigate variables and p < 0.05 was considered statistically significant. Statistically it has been shown that females have a higher possibility of unsuccessful respect of male, with a "p value" of 0.014. Another important impact factor for success of implant insertion has been represented by concomitants pathologies: cancer represents the most negative high factor risk with a percentage of unsuccessful of 50%, followed by heart disease (15%), and diabetes (3.7%). SDIs are reliable tools for difficult cases of oral rehabilitation. They have a higher success and survival rate, which means stable results over time. No differences were detected among SDI lengths, implant/crown ratio. In addition, the insertion of SDIs in banked bone can be performed without adverse effects. Finally, flapless and computer tomography-planned surgery does not significantly increase the clinical outcome of SDIs in complex rehabilitation. Cancer represents the most important variable to consider when a patient wants to do oral rehabilitation because of its high risk of unsuccessful.

Low-Dimensional Statistics of Anatomical Variability via Compact Representation of Image Deformations.

PubMed

Zhang, Miaomiao; Wells, William M; Golland, Polina

2016-10-01

Using image-based descriptors to investigate clinical hypotheses and therapeutic implications is challenging due to the notorious "curse of dimensionality" coupled with a small sample size. In this paper, we present a low-dimensional analysis of anatomical shape variability in the space of diffeomorphisms and demonstrate its benefits for clinical studies. To combat the high dimensionality of the deformation descriptors, we develop a probabilistic model of principal geodesic analysis in a bandlimited low-dimensional space that still captures the underlying variability of image data. We demonstrate the performance of our model on a set of 3D brain MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Our model yields a more compact representation of group variation at substantially lower computational cost than models based on the high-dimensional state-of-the-art approaches such as tangent space PCA (TPCA) and probabilistic principal geodesic analysis (PPGA).

Effect of climate variables on cocoa black pod incidence in Sabah using ARIMAX model

NASA Astrophysics Data System (ADS)

Ling Sheng Chang, Albert; Ramba, Haya; Mohd. Jaaffar, Ahmad Kamil; Kim Phin, Chong; Chong Mun, Ho

2016-06-01

Cocoa black pod disease is one of the major diseases affecting the cocoa production in Malaysia and also around the world. Studies have shown that the climate variables have influenced the cocoa black pod disease incidence and it is important to quantify the black pod disease variation due to the effect of climate variables. Application of time series analysis especially auto-regressive moving average (ARIMA) model has been widely used in economics study and can be used to quantify the effect of climate variables on black pod incidence to forecast the right time to control the incidence. However, ARIMA model does not capture some turning points in cocoa black pod incidence. In order to improve forecasting performance, other explanatory variables such as climate variables should be included into ARIMA model as ARIMAX model. Therefore, this paper is to study the effect of climate variables on the cocoa black pod disease incidence using ARIMAX model. The findings of the study showed ARIMAX model using MA(1) and relative humidity at lag 7 days, RHt - 7 gave better R square value compared to ARIMA model using MA(1) which could be used to forecast the black pod incidence to assist the farmers determine timely application of fungicide spraying and culture practices to control the black pod incidence.

The association between phenomena on the sun, geomagnetic activity, meteorological variables, and cardiovascular characteristic of patients with myocardial infarction.

PubMed

Vencloviene, Jone; Babarskiene, Ruta; Slapikas, Rimvydas; Sakalyte, Gintare

2013-09-01

It has been found that solar and geomagnetic activity affects the cardiovascular system. Some evidence has been reported on the increase in the rate of myocardial infarction, stroke and myocardial infarction related deaths during geomagnetic storms. We investigated the association between cardiovascular characteristics of patients, admitted for myocardial infarction with ST elevation (STEMI), and geomagnetic activity (GMA), solar proton events (SPE), solar flares, and meteorological variables during admission. The data of 1,979 patients hospitalized at the Hospital of Lithuanian University of Health Sciences (Kaunas) were analyzed. We evaluated the association between environmental variables and patient's characteristics by multivariate logistic regression, controlling patient's gender and age. Two days after geomagnetic storms the risk of STEMI was over 1.5 times increased in patients who had a medical history of myocardial infarction, stable angina, renal or pulmonary diseases. The dose-response association between GMA level and STEMI risk for patients with renal diseases in history was observed. Two days after SPE the risk of STEMI in patients with stable angina in anamnesis was increased over 1.5 times, adjusting by GMA level. The SPE were associated with an increase of risk for patients with renal diseases in history. This study confirms the strongest effect of phenomena in the Sun in high risk patients.

Refractory periods and climate forcing in cholera dynamics.

PubMed

Koelle, Katia; Rodó, Xavier; Pascual, Mercedes; Yunus, Md; Mostafa, Golam

2005-08-04

Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year. Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity. Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain (El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods (over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods (under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Niño-Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing.

Association Between Weather Variables, Airborne Inoculum Concentration, and Raspberry Fruit Rot Caused by Botrytis cinerea.

PubMed

Carisse, Odile; McNealis, Vanessa; Kriss, Alissa

2018-01-01

Botrytis fruit rot (BFR), one of the most important diseases of raspberry (Rubus spp.), is controlled primarily with fungicides. Despite the use of fungicides, crop losses due to BFR are high in most years. The aim of this study was to investigate the association between airborne inoculum, weather variables, and BFR in order to improve the management of the disease as well as harvest and storage decisions. Crop losses, measured as the percentage of diseased berries during the harvest period, were monitored in unsprayed field plots at four sites in three successive years, together with meteorological data and the number of conidia in the air. Based on windowpane analysis, there was no evidence of correlation between crop losses and temperature, vapor pressure deficit, wind, solar radiation, or probability of infection. There were significant correlations between crop losses and airborne inoculum and between crop losses and humidity-related variables, and the best window length was identified as 7 days. Using 7-day average airborne inoculum concentration combined with 7-day average relative humidity for periods ending 6 to 8 days before bloom, it was possible to accurately predict crop losses (R 2 of 0.86 to 0.89). These models could be used to assist with managing BFR, timing harvests, and optimizing storage duration in raspberry crops.

TEPAPA: a novel in silico feature learning pipeline for mining prognostic and associative factors from text-based electronic medical records.

PubMed

Lin, Frank Po-Yen; Pokorny, Adrian; Teng, Christina; Epstein, Richard J

2017-07-31

Vast amounts of clinically relevant text-based variables lie undiscovered and unexploited in electronic medical records (EMR). To exploit this untapped resource, and thus facilitate the discovery of informative covariates from unstructured clinical narratives, we have built a novel computational pipeline termed Text-based Exploratory Pattern Analyser for Prognosticator and Associator discovery (TEPAPA). This pipeline combines semantic-free natural language processing (NLP), regular expression induction, and statistical association testing to identify conserved text patterns associated with outcome variables of clinical interest. When we applied TEPAPA to a cohort of head and neck squamous cell carcinoma patients, plausible concepts known to be correlated with human papilloma virus (HPV) status were identified from the EMR text, including site of primary disease, tumour stage, pathologic characteristics, and treatment modalities. Similarly, correlates of other variables (including gender, nodal status, recurrent disease, smoking and alcohol status) were also reliably recovered. Using highly-associated patterns as covariates, a patient's HPV status was classifiable using a bootstrap analysis with a mean area under the ROC curve of 0.861, suggesting its predictive utility in supporting EMR-based phenotyping tasks. These data support using this integrative approach to efficiently identify disease-associated factors from unstructured EMR narratives, and thus to efficiently generate testable hypotheses.

The association between phenomena on the Sun, geomagnetic activity, meteorological variables, and cardiovascular characteristic of patients with myocardial infarction

NASA Astrophysics Data System (ADS)

Vencloviene, Jone; Babarskiene, Ruta; Slapikas, Rimvydas; Sakalyte, Gintare

2013-09-01

It has been found that solar and geomagnetic activity affects the cardiovascular system. Some evidence has been reported on the increase in the rate of myocardial infarction, stroke and myocardial infarction related deaths during geomagnetic storms. We investigated the association between cardiovascular characteristics of patients, admitted for myocardial infarction with ST elevation (STEMI), and geomagnetic activity (GMA), solar proton events (SPE), solar flares, and meteorological variables during admission. The data of 1,979 patients hospitalized at the Hospital of Lithuanian University of Health Sciences (Kaunas) were analyzed. We evaluated the association between environmental variables and patient's characteristics by multivariate logistic regression, controlling patient's gender and age. Two days after geomagnetic storms the risk of STEMI was over 1.5 times increased in patients who had a medical history of myocardial infarction, stable angina, renal or pulmonary diseases. The dose-response association between GMA level and STEMI risk for patients with renal diseases in history was observed. Two days after SPE the risk of STEMI in patients with stable angina in anamnesis was increased over 1.5 times, adjusting by GMA level. The SPE were associated with an increase of risk for patients with renal diseases in history. This study confirms the strongest effect of phenomena in the Sun in high risk patients.

Genetic Susceptibility to Cardiac and Digestive Clinical Forms of Chronic Chagas Disease: Involvement of the CCR5 59029 A/G Polymorphism

PubMed Central

de Oliveira, Amanda Priscila; Bernardo, Cássia Rubia; Camargo, Ana Vitória da Silveira; Ronchi, Luiz Sérgio; Borim, Aldenis Albaneze; Brandão de Mattos, Cinara Cássia; de Campos Júnior, Eumildo; Castiglioni, Lílian; Netinho, João Gomes; Cavasini, Carlos Eugênio; Bestetti, Reinaldo Bulgarelli; de Mattos, Luiz Carlos

2015-01-01

The clinical manifestations of chronic Chagas disease include the cardiac form of the disease and the digestive form. Not all the factors that act in the variable clinical course of this disease are known. This study investigated whether the CCR5Δ32 (rs333) and CCR5 59029 A/G (promoter region—rs1799987) polymorphisms of the CCR5 gene are associated with different clinical forms of chronic Chagas disease and with the severity of left ventricular systolic dysfunction in patients with chronic Chagas heart disease (CCHD). The antibodies anti-T. cruzi were identified by ELISA. PCR and PCR-RFLP were used to identify the CCR5Δ32 and CCR5 59029 A/G polymorphisms. The chi-square test was used to compare variables between groups. There was a higher frequency of the AA genotype in patients with CCHD compared with patients with the digestive form of the disease and the control group. The results also showed a high frequency of the AG genotype in patients with the digestive form of the disease compared to the other groups. The results of this study show that the CCR5Δ32 polymorphism does not seem to influence the different clinical manifestations of Chagas disease but there is involvement of the CCR5 59029 A/G polymorphism in susceptibility to the different forms of chronic Chagas disease. Besides, these polymorphisms do not influence left ventricular systolic dysfunction in patients with CCHD. PMID:26599761

Variability of serial same-day left ventricular ejection fraction using quantitative gated SPECT.

PubMed

Vallejo, Enrique; Chaya, Hugo; Plancarte, Gerardo; Victoria, Diana; Bialostozky, David

2002-01-01

The accuracy of quantitative gated single photon emission computed tomography (SPECT) (QGS) and the potential limitations for estimation of left ventricular ejection fraction (LVEF) have been extensively evaluated. However, few studies have focused on the serial variability of QGS. This study was conducted to assess the serial variability of QGS for determination of LVEF between 2 sequential technetium 99m sestamibi-gated SPECT acquisitions at rest in both healthy and unhealthy subjects. The study population consisted of 2 groups: group I included 21 volunteers with a low likelihood of CAD, and group II included 22 consecutive patients with documented CAD. Both groups underwent serial SPECT imaging. The overall correlation between sequential images was high (r = 0.94, SEE = 5.3%), and the mean serial variability of LVEF was 5.15% +/- 3.51%. Serial variability was lower for images with high counts (3.45% +/- 3.23%) than for images with low counts (6.85% +/- 3.77%). The mean serial variability was not different between normal and abnormal high-dose images (3.0% +/- 1.56% vs 3.9% +/- 2.77%). However, mean serial variability for images derived from abnormal low-dose images was significantly greater than that derived from normal low-dose images (9.6% +/- 2.22% vs 3.1% +/- 2.12%, P <.05). Although QGS is an efficacious method to approximate LVEF values and is extremely valuable for incremental risk stratification of patients with coronary artery disease, it has significant variability in the estimation of LVEF on serial images. This should be taken into account when used for serial evaluation of LVEF.

Anthropometrics and Body Composition in Adults with High-Grade Gliomas: Effects of Disease-Related Variables.

PubMed

Bertoli, Simona; Battezzati, Alberto; Petruzzi, Alessandra; Leone, Alessandro; De Amicis, Ramona; Tramacere, Elena; Meda, Maddalena; Foppiani, Andrea; Silvani, Antonio; Lamperti, Elena

2018-04-01

Nutritional status in adults with high-grade gliomas (HGGs) has been poorly investigated. We studied anthropometrics and fat mass (FM), fat free mass (FFM), and body water in HGGs patients also in relation to disease-related variables. Fifty-one patients (17 III and 34 IV-grade) and fifty-one control group (CG) matched for sex, age, and BMI were enrolled. Neurological scales, anthropometry, bioimpedance, and blood sampling were performed and analyzed according to grade, lesion location, extent of resection, phase of treatment, current steroids and antiepileptic therapy, and age of patient. 41.2% were overweight and 15.7% obese. Compared to the CG, HGGs had similar anthropometrics and body composition. IV-grade, compared to the III, had higher BMI, waist circumference, FM and lower FFM. Only patients during concomitant radio and chemotherapy showed a negative BMI variation from baseline. In conclusion, overnutrition occurs in almost 6 out of 10 HGGs patients and is more relevant in IV-grade. Throughout all the treatment phases, there is a higher risk of weight loss occurred only during concomitant radio and chemotherapy. Body composition showed no specific features compared to controls. These results may assist intervention studies directed towards neurometabolic dietary treatment. Nutritional screening is warranted during the time course of disease.

ABCC6 and Pseudoxanthoma Elasticum: The Face of a Rare Disease from Genetics to Advocacy

PubMed Central

Moitra, Karobi; Garcia, Sonia; Etoundi, Clementine; Cooper, Donna; Roland, Anna; Dixon, Patrice; Reyes, Sandra; Turan, Sevilay; Dean, Michael

2017-01-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by the mineralization of connective tissues in the body. Primary manifestation of PXE occurs in the tissues of the skin, eyes, and cardiovascular system. PXE is primarily caused by mutations in the ABCC6 gene. The ABCC6 gene encodes the trans-membrane protein ABCC6, which is highly expressed in the kidneys and liver. PXE has high phenotypic variability, which may possibly be affected by several modifier genes. Disease advocacy organizations have had a pivotal role in bringing rare disease research to the forefront and in helping to sustain research funding for rare genetic diseases in order to help find a treatment for these diseases, pseudoxanthoma elasticum included. Because of these initiatives, individuals affected by these conditions benefit by being scientifically informed about their condition, having an effective support mechanism, and also by contributing to scientific research efforts and banking of biological samples. This rapid progress would not have been possible without the aid of disease advocacy organizations such as PXE International. PMID:28696355

An Examination of the Demographic and Environmental Variables Correlated with Lyme Disease Emergence in Virginia.

PubMed

Seukep, Sara E; Kolivras, Korine N; Hong, Yili; Li, Jie; Prisley, Stephen P; Campbell, James B; Gaines, David N; Dymond, Randel L

2015-12-01

Lyme disease is the United States' most significant vector-borne illness. Virginia, on the southern edge of the disease's currently expanding range, has experienced an increase in Lyme disease both spatially and temporally, with steadily increasing rates over the past decade and disease spread from the northern to the southwestern part of the state. This study used a Geographic Information System and a spatial Poisson regression model to examine correlations between demographic and land cover variables, and human Lyme disease from 2006 to 2010 in Virginia. Analysis indicated that herbaceous land cover is positively correlated with Lyme disease incidence rates. Areas with greater interspersion between herbaceous and forested land were also positively correlated with incidence rates. In addition, income and age were positively correlated with incidence rates. Levels of development, interspersion of herbaceous and developed land, and population density were negatively correlated with incidence rates. Abundance of forest fragments less than 2 hectares in area was not significantly correlated. Our results support some findings of previous studies on ecological variables and Lyme disease in endemic areas, but other results have not been found in previous studies, highlighting the potential contribution of new variables as Lyme disease continues to emerge southward.

[Subclinical and established kidney disease in recently diagnosed hypertensive patients].

PubMed

Gómez-Marcos, Manuel Angel; Martínez-Salgado, Carlos; Grandes, Gonzalo; Recio-Rodríguez, José Ignacio; Castaño Sánchez, Yolanda; Rodríguez Sánchez, Emiliano; García-Ortiz, Luis

2010-03-06

To estimate renal disease in recently diagnosed hypertensive patients, and to identify factors related to renal disease. Cross-sectional study, with 425 hypertensive patients recently diagnosed in primary health care; renal disease was estimated with serum creatinine, albumin/creatinine index and glomerular filtration rate (GFR). We analyzed cardiovascular risk factors (CRF), subclinical organ injury and cardiovascular disease following the criteria of the 2007 European Guide of Hypertension. Average age: 58,96 +/- 12,73 years old, 63,3% male. We found dyslipemia in 80%, abdominal obesity in 49% and metabolic syndrome in 36% patients. These patients showed increased serum creatinine 3,3%, a reduction in GFR 9,6%, hidden renal disease 6,4%, microalbuminuria 7,5% and nephropathy 2,4%. Hypertensive patients with renal disease (17,88%) were older, with higher systolic pressure, higher incidence of metabolic syndrome, abnormal carotid intima-media thickness and ankle-arm index, and presence of cardiovascular disease. Variables associated with renal disease were metabolic syndrome (odds ratio = 11,12) and ankle-arm index (odds ratio = 17,55). Variables related to creatinina were sex, ankle-arm index and metabolic syndrome; variables related to GFR were sex, age, ankle-arm index, metabolic syndrome and body mass index (BMI); variables related with albumin/creatinine index included diabetes mellitus. Renal disease is detected in about 2 out of 10 hypertensive patients, when, besides serum creatinina, we analyze albumin/creatinine index and GFR. Metabolic syndrome and ankle-arm index are the main variables associated with renal disease. Copyright 2009 Elsevier España, S.L. All rights reserved.

Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease.

PubMed

Lindholm, Daniel; Lindbäck, Johan; Armstrong, Paul W; Budaj, Andrzej; Cannon, Christopher P; Granger, Christopher B; Hagström, Emil; Held, Claes; Koenig, Wolfgang; Östlund, Ollie; Stewart, Ralph A H; Soffer, Joseph; White, Harvey D; de Winter, Robbert J; Steg, Philippe Gabriel; Siegbahn, Agneta; Kleber, Marcus E; Dressel, Alexander; Grammer, Tanja B; März, Winfried; Wallentin, Lars

2017-08-15

Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD). This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD. In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study. During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This "ABC-CHD" model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts. This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Screening for periodontal disease in research dogs - a methodology study.

PubMed

Kortegaard, Hanne E; Eriksen, Thomas; Baelum, Vibeke

2014-11-19

It has been shown that the prevalence of both clinical attachment loss (CAL) ≥1 mm and pocket probing depth (PPD) ≥4 mm is relatively high even in younger dogs, but also that only a minority of the dogs have such clinical signs of periodontal disease (PD) in more than a few teeth. Hence, a minority of dogs carry the major PD burden. These epidemiological features suggest that screening for PD in larger groups of dogs, allowing for rapid assessment of treatment planning, or for the selection of dogs with or without PD prior to be included in experimental trials, should be possible. CAL is the central variable in assessing PD extent and severity while PPD is the central variable used in treatment planning which make these two variables obvious in a screening protocol with the dual aim of disease identification and treatment planning. The main purpose of the present study in 98 laboratory Beagle dogs was to construct a fast, simple and accurate screening tool, which is highly sensitive for the identification of dogs with PD. Examination of the maxillary P4, P3, P2, I1 and C would, in this population, result in the identification of 85.5% of all dogs and 96% of all teeth positive for CAL ≥1 mm, and 58.9% of all dogs and 82.1% of all teeth positive for PD ≥4 mm. Examination of tooth pairs, all C's, maxillary I2, M2 and the mandibular P4 would, in this population result in identification of 92.9% of all dogs and 97.3% of all teeth positive for PD ≥4 mm, and 65.5% of all dogs and 83.2% of all teeth positive for CAL ≥1 mm. The results presented here only pertain to the present study population. This screening protocol is suitable for examination of larger groups of laboratory Beagle dogs for PD and our findings indicate that diseased dogs are identified with a high degree of sensitivity. Before this screening can be used in clinical practice, it has to be validated in breeds other than Beagle dogs and in populations with larger age variation.

Hantavirus pulmonary syndrome clinical findings: evaluating a surveillance case definition.

PubMed

Knust, Barbara; Macneil, Adam; Rollin, Pierre E

2012-05-01

Clinical cases of hantavirus pulmonary syndrome (HPS) can be challenging to differentiate from other acute respiratory diseases, which can lead to delays in diagnosis, treatment, and disease reporting. Rapid onset of severe disease occurs, at times before diagnostic test results are available. This study's objective was to examine the clinical characteristics of patients that would indicate HPS to aid in detection and reporting. Test results of blood samples from U.S. patients suspected of having HPS submitted to the Centers for Disease Control and Prevention from 1998-2010 were reviewed. Patient information collected by case report forms was compared between HPS-confirmed and test-negative patients. Diagnostic sensitivity, specificity, predictive values, and likelihood ratios were calculated for individual clinical findings and combinations of variables. Of 567 patients included, 36% were HPS-confirmed. Thrombocytopenia, chest x-rays with suggestive signs, and receiving supplemental oxygenation were highly sensitive (>95%), while elevated hematocrit was highly specific (83%) in detecting HPS. Combinations that maximized sensitivity required the presence of thrombocytopenia. Using a national sample of suspect patients, we found that thrombocytopenia was a highly sensitive indicator of HPS and should be included in surveillance definitions for suspected HPS. Using a sensitive suspect case definition to identify potential HPS patients that are confirmed by highly specific diagnostic testing will ensure accurate reporting of this disease.

Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

PubMed

Roede, James R; Uppal, Karan; Park, Youngja; Lee, Kichun; Tran, Vilinh; Walker, Douglas; Strobel, Frederick H; Rhodes, Shannon L; Ritz, Beate; Jones, Dean P

2013-01-01

Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

Systematic Analysis of the Genetic Variability That Impacts SUMO Conjugation and Their Involvement in Human Diseases

NASA Astrophysics Data System (ADS)

Xu, Hao-Dong; Shi, Shao-Ping; Chen, Xiang; Qiu, Jian-Ding

2015-07-01

Protein function has been observed to rely on select essential sites instead of requiring all sites to be indispensable. Small ubiquitin-related modifier (SUMO) conjugation or sumoylation, which is a highly dynamic reversible process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified, has shown to be especially valuable in cellular biology. Motivated by the significance of SUMO conjugation in biological processes, we report here on the first exploratory assessment whether sumoylation related genetic variability impacts protein functions as well as the occurrence of diseases related to SUMO. Here, we defined the SUMOAMVR as sumoylation related amino acid variations that affect sumoylation sites or enzymes involved in the process of connectivity, and categorized four types of potential SUMOAMVRs. We detected that 17.13% of amino acid variations are potential SUMOAMVRs and 4.83% of disease mutations could lead to SUMOAMVR with our system. More interestingly, the statistical analysis demonstrates that the amino acid variations that directly create new potential lysine sumoylation sites are more likely to cause diseases. It can be anticipated that our method can provide more instructive guidance to identify the mechanisms of genetic diseases.

Complex social contagion makes networks more vulnerable to disease outbreaks.

PubMed

Campbell, Ellsworth; Salathé, Marcel

2013-01-01

Social network analysis is now widely used to investigate the dynamics of infectious disease spread. Vaccination dramatically disrupts disease transmission on a contact network, and indeed, high vaccination rates can potentially halt disease transmission altogether. Here, we build on mounting evidence that health behaviors - such as vaccination, and refusal thereof - can spread across social networks through a process of complex contagion that requires social reinforcement. Using network simulations that model health behavior and infectious disease spread, we find that under otherwise identical conditions, the process by which the health behavior spreads has a very strong effect on disease outbreak dynamics. This dynamic variability results from differences in the topology within susceptible communities that arise during the health behavior spreading process, which in turn depends on the topology of the overall social network. Our findings point to the importance of health behavior spread in predicting and controlling disease outbreaks.

Space-time variability of citrus leprosis as strategic planning for crop management.

PubMed

Andrade, Daniel J; Lorençon, José R; Siqueira, Diego S; Novelli, Valdenice M; Bassanezi, Renato B

2018-01-31

Citrus leprosis is the most important viral disease of citrus. Knowledge of its spatiotemporal structure is fundamental to a representative sampling plan focused on the disease control approach. Such a well-crafted sampling design helps to reduce pesticide use in agriculture to control pests and diseases. Despite the use of acaricides to control citrus leprosis vector (Brevipalpus spp.) populations, the disease has spread rapidly through experimental areas. Citrus leprosis has an aggregate spatial distribution, with high dependence among symptomatic plants. Temporal variation in disease incidence increased among symptomatic plants by 4% per month. Use of acaricides alone to control the vector of leprosis is insufficient to avoid its incidence in healthy plants. Preliminary investigation into the time and space variation in the incidence of the disease is fundamental to select a sampling plan and determine effective strategies for disease management. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Disease in a more variable and unpredictable climate

NASA Astrophysics Data System (ADS)

McMahon, T. A.; Raffel, T.; Rohr, J. R.; Halstead, N.; Venesky, M.; Romansic, J.

2014-12-01

Global climate change is shifting the dynamics of infectious diseases of humans and wildlife with potential adverse consequences for disease control. Despite this, the role of global climate change in the decline of biodiversity and the emergence of infectious diseases remains controversial. Climate change is expected to increase climate variability in addition to increasing mean temperatures, making climate less predictable. However, few empirical or theoretical studies have considered the effects of climate variability or predictability on disease, despite it being likely that hosts and parasites will have differential responses to climatic shifts. Here we present a theoretical framework for how temperature variation and its predictability influence disease risk by affecting host and parasite acclimation responses. Laboratory experiments and field data on disease-associated frog declines in Latin America support this framework and provide evidence that unpredictable temperature fluctuations, on both monthly and diurnal timescales, decrease frog resistance to the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Furthermore, the pattern of temperature-dependent growth of the fungus on frogs was inconsistent with the pattern of Bd growth in culture, emphasizing the importance of accounting for the host-parasite interaction when predicting climate-dependent disease dynamics. Consistent with our laboratory experiments, increased regional temperature variability associated with global El Niño climatic events was the best predictor of widespread amphibian losses in the genus Atelopus. Thus, incorporating the effects of small-scale temporal variability in climate can greatly improve our ability to predict the effects of climate change on disease.

Contribution of ethnic group and socioeconomic status to degree of disability in rheumatoid arthritis in Chilean patients.

PubMed

Alarcón, Ana M; Muñoz, Sergio; Kaufman, Jay S; Martínez, Carlos; Riedemann, Pablo; Kaliski, Sonia

2015-04-01

The aim of this study was to estimate the contributions of ethnic group and socioeconomic status as social determinants related to disability and disease activity in Chilean Mapuche and non-Mapuche patients with rheumatoid arthritis (RA). Descriptive cross-sectional study with a stratified hospital-based sample of 189 patients in treatment with disease-modifying anti-rheumatic drugs. We assessed disability as categorical variable with the Health Assessment Questionnaire, disease activity with the Disease Activity Score instrument, and socioeconomic status with a standard questionnaire used by the Chilean government. Measures of association, stratified analyses and a multiple logistic regression model were used to analyze the data using the Stata 12.1 software package. Low socioeconomic status (annual income below US$ 7,200) is associated with disability (OR 3.87 CI 1.68-9.20) and Mapuche ethnic identity also contributes to disability (OR 2.48, CI 1.09-5.89). Relevant but not statistically significant in multivariable models were variables such as age, gender and place of residence. RA patients with a low socioeconomic status have almost three times the odds of having a moderate to high disability, independent of their ethnic group, gender or place of residence. Therefore, healthcare efforts should be aimed at promoting early diagnosis and prompt treatment among populations with high levels of poverty, which in the region of the Araucanía means primarily indigenous rural areas.

Body temperature variability (Part 2): masking influences of body temperature variability and a review of body temperature variability in disease.

PubMed

Kelly, Gregory S

2007-03-01

This is the second of a two-part review on body temperature variability. Part 1 discussed historical and modern findings on average body temperatures. It also discussed endogenous sources of temperature variability, including variations caused by site of measurement; circadian, menstrual, and annual biological rhythms; fitness; and aging. Part 2 reviews the effects of exogenous masking agents - external factors in the environment, diet, or lifestyle that can be a significant source of body temperature variability. Body temperature variability findings in disease states are also reviewed.

High Throughput Screening for Anti–Trypanosoma cruzi Drug Discovery

PubMed Central

Alonso-Padilla, Julio; Rodríguez, Ana

2014-01-01

The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease, stands as a fundamental need. Currently, there are only two drugs available to treat this neglected disease, which represents a major public health problem in Latin America. Both available therapies, benznidazole and nifurtimox, have significant toxic side effects and their efficacy against the life-threatening symptomatic chronic stage of the disease is variable. Thus, there is an urgent need for new, improved anti–T. cruzi drugs. With the objective to reliably accelerate the drug discovery process against Chagas disease, several advances have been made in the last few years. Availability of engineered reporter gene expressing parasites triggered the development of phenotypic in vitro assays suitable for high throughput screening (HTS) as well as the establishment of new in vivo protocols that allow faster experimental outcomes. Recently, automated high content microscopy approaches have also been used to identify new parasitic inhibitors. These in vitro and in vivo early drug discovery approaches, which hopefully will contribute to bring better anti–T. cruzi drug entities in the near future, are reviewed here. PMID:25474364

High throughput screening for anti-Trypanosoma cruzi drug discovery.

PubMed

Alonso-Padilla, Julio; Rodríguez, Ana

2014-12-01

The discovery of new therapeutic options against Trypanosoma cruzi, the causative agent of Chagas disease, stands as a fundamental need. Currently, there are only two drugs available to treat this neglected disease, which represents a major public health problem in Latin America. Both available therapies, benznidazole and nifurtimox, have significant toxic side effects and their efficacy against the life-threatening symptomatic chronic stage of the disease is variable. Thus, there is an urgent need for new, improved anti-T. cruzi drugs. With the objective to reliably accelerate the drug discovery process against Chagas disease, several advances have been made in the last few years. Availability of engineered reporter gene expressing parasites triggered the development of phenotypic in vitro assays suitable for high throughput screening (HTS) as well as the establishment of new in vivo protocols that allow faster experimental outcomes. Recently, automated high content microscopy approaches have also been used to identify new parasitic inhibitors. These in vitro and in vivo early drug discovery approaches, which hopefully will contribute to bring better anti-T. cruzi drug entities in the near future, are reviewed here.

Effectiveness of planned teaching program on knowledge regarding Alzheimer's disease among the family members of elderly in a selected urban community at Mangalore

PubMed Central

Rodrigues, Lavina; Mathias, Thereza

2016-01-01

Background: Alzheimer's disease is one of the debilitating chronic diseases among older persons. It is an irreversible condition that leads to progressive deterioration of cognitive, intellectual, physical, and psychosocial functions. The study was aimed to assess the knowledge of the family members of elderly regarding Alzheimer's disease in a selected urban community at Mangalore. Materials and Methods: A preexperimental research design of one group pretest and posttest with an evaluative approach was adopted for the study. A total of 50 family members of elderly who met the inclusion criteria were selected through purposive sampling technique. The researcher developed a planned teaching program on Alzheimer's disease, and structured knowledge questionnaire on Alzheimer's disease was used to collect the data. Results: Descriptive and inferential statistics was used to analyze the data. Analysis revealed that the mean posttest knowledge (20.78 ± 3.31) was higher than mean pretest knowledge scores (12.90 ± 2.43). Significance of difference between pretest and posttest was statistically tested using paired “t” test and it was found very highly significant (t = 40.85, P < 0.05). Majority of the variables showed no significant association between pretest and posttest knowledge score and with demographic variables. Conclusion: The findings revealed that the planned teaching program is an effective strategy for improving the knowledge of the subjects. PMID:26985104

Effectiveness of planned teaching program on knowledge regarding Alzheimer's disease among the family members of elderly in a selected urban community at Mangalore.

PubMed

Rodrigues, Lavina; Mathias, Thereza

2016-01-01

Alzheimer's disease is one of the debilitating chronic diseases among older persons. It is an irreversible condition that leads to progressive deterioration of cognitive, intellectual, physical, and psychosocial functions. The study was aimed to assess the knowledge of the family members of elderly regarding Alzheimer's disease in a selected urban community at Mangalore. A preexperimental research design of one group pretest and posttest with an evaluative approach was adopted for the study. A total of 50 family members of elderly who met the inclusion criteria were selected through purposive sampling technique. The researcher developed a planned teaching program on Alzheimer's disease, and structured knowledge questionnaire on Alzheimer's disease was used to collect the data. Descriptive and inferential statistics was used to analyze the data. Analysis revealed that the mean posttest knowledge (20.78 ± 3.31) was higher than mean pretest knowledge scores (12.90 ± 2.43). Significance of difference between pretest and posttest was statistically tested using paired "t" test and it was found very highly significant (t = 40.85, P < 0.05). Majority of the variables showed no significant association between pretest and posttest knowledge score and with demographic variables. The findings revealed that the planned teaching program is an effective strategy for improving the knowledge of the subjects.

Rheumatoid arthritis-related interstitial lung disease (RA-ILD): methotrexate and the severity of lung disease are associated to prognosis.

PubMed

Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Pérez-Román, Diana I; Pérez-Dorame, Renzo; Mateos-Toledo, Heidegger; Mejía, Mayra

2017-07-01

Interstitial lung disease (ILD) is a severe rheumatoid arthritis (RA) manifestation. The worst survival has been associated with usual interstitial pneumonia (UIP) definitive pattern in high-resolution chest tomography (HRCT) scans. Moreover, the use of methotrexate in RA-ILD is controversial. Our aim was to evaluate prognostic factors including methotrexate in an RA-ILD cohort and their association with survival. RA-ILD patients referred for medical evaluation and treatment at a single center were included. At the baseline, pulmonary function tests were carried out and a HRCT was obtained. A radiologist evaluated the ILD tomographic pattern and the extent of lung disease. Patients were considered as receiving methotrexate therapy if this drug was specifically prescribed for the treatment of RA-ILD at the beginning of follow up. Seventy-eight patients were included. UIP definite pattern in HRCT was not associated to worse survival. Variables associated with mortality reflected the severity of lung disease. Treatment with methotrexate was associated with survival (HR 0.13, 95% CI 0.02-0.64); older patients had worse prognosis (HR 1.04, 95% CI 1.003-1.09). After adjusting for confounding variables, methotrexate was strongly associated with survival. Methotrexate treatment during follow up was associated with survival. The severity of lung disease and not the tomographic pattern is associated with mortality; older patients had worse prognosis.

Frequent occurrence of cytomegalovirus retinitis during immune reconstitution warrants regular ophthalmic screening in high-risk pediatric allogeneic hematopoietic stem cell transplant recipients.

PubMed

Hiwarkar, Prashant; Gajdosova, Eva; Qasim, Waseem; Worth, Austen; Breuer, Judith; Chiesa, Robert; Ridout, Deborah; Edelsten, Clive; Moore, Anthony; Amrolia, Persis; Veys, Paul; Rao, Kanchan

2014-06-01

Although cytomegalovirus (CMV) retinitis (CMVR) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT), standard operating procedures for ophthalmic monitoring are variable. In particular, authors perceived a greater risk of CMVR after pediatric HSCT for inherited immunodeficiencies, in patients who often have pretransplantation viremia. This study was therefore performed to identify high-risk pediatric HSCT recipients who would benefit from regular ophthalmic monitoring. During a 5-year study period, we retrospectively analyzed findings in 56 of 304 consecutive HSCT recipients (age range, 0.5-197 months) in whom significant CMV viremia developed (CMV level at PCR, ≥4000 copies/mL). All HSCT recipients with significant CMV viremia underwent retinal examination weekly (inpatients) or every other week (outpatients), with examinations performed by a skilled ophthalmologist. CMVR developed in 13 (4%) of 304 HSCT recipients, 23% (13 of 56) of those with significant CMV viremia. Pretransplant viremia (odds ratio, 11.3; P < .01), acute (grade ≥2) graft-vs-host disease (odds ratio, 8.2; P < .02) and mismatched graft (odds ratio, 8; P < .02) were identified as independent risk factors. Compared with other invasive CMV diseases, CMVR was more often a late-onset disease, occurring at a median of 199 days after HSCT. At diagnosis, a significantly higher CD4 T-cell count (≥200/µL; P < .03) and a lower CMV load (P < .004) was observed in children with CMVR, compared with those in whom lung, gut, or liver CMV disease developed. We report an increased risk of CMVR in high-risk pediatric HSCT recipients. This form of CMV disease differs from other invasive CMV disease in its relationship to immune reconstitution and viral dynamics. We have studied the relationship between these variables and suggested a risk-stratified ophthalmic screening strategy. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Habitat Suitability Model for the Distribution of Ixodes scapularis (Acari: Ixodidae) in Minnesota

PubMed Central

Johnson, T. L.; Bjork, J. K. H.; Neitzel, D. F.; Dorr, F. M.; Schiffman, E. K.; Eisen, R. J.

2016-01-01

Ixodes scapularis Say, the black-legged tick, is the primary vector in the eastern United States of several pathogens causing human diseases including Lyme disease, anaplasmosis, and babesiosis. Over the past two decades, I. scapularis-borne diseases have increased in incidence as well as geographic distribution. Lyme disease exists in two major foci in the United States, one encompassing northeastern states and the other in the Upper Midwest. Minnesota represents a state with an appreciable increase in counties reporting I. scapularis-borne illnesses, suggesting geographic expansion of vector populations in recent years. Recent tick distribution records support this assumption. Here, we used those records to create a fine resolution, subcounty-level distribution model for I. scapularis using variable response curves in addition to tests of variable importance. The model identified 19% of Minnesota as potentially suitable for establishment of the tick and indicated with high accuracy (AUC = 0.863) that the distribution is driven by land cover type, summer precipitation, maximum summer temperatures, and annual temperature variation. We provide updated records of established populations near the northwestern species range limit and present a model that increases our understanding of the potential distribution of I. scapularis in Minnesota. PMID:27026161

Health education literacy in patients with chronic musculoskeletal diseases: development of a new questionnaire and sociodemographic predictors.

PubMed

Farin, Erik; Ullrich, Antje; Nagl, Michaela

2013-12-01

It was our aim to develop a questionnaire for patients with chronic musculoskeletal diseases to self-report their health education literacy, to analyse the psychometric properties of the instrument and to test hypotheses concerning sociodemographic predictors of health education literacy. A total of 577 patients with chronic back pain or osteoarthritis who underwent inpatient rehabilitation were surveyed. The resulting 'HELP questionnaire' (health education literacy of patients with chronic musculoskeletal diseases) consists of 18 items and three scales (comprehension of medical information, applying medical information, communicative competence in provider interactions). The instrument's psychometric properties are good (Cronbach's alpha between 0.88 and 0.95, unidimensionality and Rasch model fit established). Our sample's average level of self-reported health education literacy is quite high. However, 20-30% of the patients admitted to having difficulty understanding important aspects of health education programmes (i.e. comprehending what medical information means in relation to their disease). The variance explained by sociodemographic and basic medical variables is small (4-8%). Greater effort is required to make health education programmes easier to understand. There is a need for more research on interindividual variability of complex aspects of health literacy.

Variably Protease-Sensitive Prionopathy: A New Sporadic Disease of the Prion Protein

PubMed Central

Zou, Wen-Quan; Puoti, Gianfranco; Xiao, Xiangzhu; Yuan, Jue; Qing, Liuting; Cali, Ignazio; Shimoji, Miyuki; Langeveld, Jan P. M.; Castellani, Rudy; Notari, Silvio; Crain, Barbara; Schmidt, Robert E.; Geschwind, Michael; DeArmond, Stephen J.; Cairns, Nigel J.; Dickson, Dennis; Honig, Lawrence; Torres, Juan Maria; Mastrianni, James; Capellari, Sabina; Giaccone, Giorgio; Belay, Ermias D.; Schonberger, Lawrence B.; Cohen, Mark; Perry, George; Kong, Qingzhong; Parchi, Piero; Tagliavini, Fabrizio; Gambetti, Pierluigi

2011-01-01

Objective The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV). Methods Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative evaluation at the National Prion Disease Pathology Surveillance Center for clinical, histopathologic, immunohistochemical, genotypical, and PrP characteristics. Results Disease duration (between 22 and 45 months) was significantly different in the 129VV and 129MV subjects. Most other phenotypic features along with the PrP electrophoretic profile were similar but distinguishable in the 3 129 genotypes. A major difference laid in the sensitivity to protease digestion of the disease-associated PrP, which was high in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This difference prompted the substitution of the original designation with “variably protease-sensitive prionopathy” (VPSPr). None of the subjects had mutations in the PrP gene coding region. Interpretation Because all 3 129 genotypes are involved, and are associated with distinguishable phenotypes, VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease, originally reported in 1920. However, the characteristics of the abnormal prion protein suggest that VPSPr is different from typical prion diseases, and perhaps more akin to subtypes of Gerstmann-Sträussler-Scheinker disease. PMID:20695009

Highly Accurate Antibody Assays for Early and Rapid Detection of Tuberculosis in African and Asian Elephants

USDA-ARS?s Scientific Manuscript database

Tuberculosis (TB) in elephants is a re-emerging zoonotic disease caused primarily by Mycobacterium tuberculosis. Current methods for screening and diagnosis rely on trunk wash culture, which has serious limitations due to low test sensitivity, slow turn-around time, and variable sample quality. Inn...

Nanobody based immunoassay for human soluble epoxide hydrolase detection using polyHRP for signal enhancement—the rediscovery of polyHRP

USDA-ARS?s Scientific Manuscript database

Soluble epoxide hydrolase (sEH) is a potential pharmacological target for treating hypertension, vascular inflammation, cancer, pain and multiple cardiovascular related diseases. A variable domain of a heavy chain only antibody (termed sdAb, nanobody or VHH) possesses advantages of small size, high ...

High probability of avian influenza virus (H7N7) transmission from poultry to humans active in disease control on infected farms.

PubMed

Bos, Marian E H; Te Beest, Dennis E; van Boven, Michiel; van Beest Holle, Mirna Robert-Du Ry; Meijer, Adam; Bosman, Arnold; Mulder, Yonne M; Koopmans, Marion P G; Stegeman, Arjan

2010-05-01

An epizootic of avian influenza (H7N7) caused a large number of human infections in The Netherlands in 2003. We used data from this epizootic to estimate infection probabilities for persons involved in disease control on infected farms. Analyses were based on databases containing information on the infected farms, person-visits to these farms, and exposure variables (number of birds present, housing type, poultry type, depopulation method, period during epizootic). Case definition was based on self-reported conjunctivitis and positive response to hemagglutination inhibition assay. A high infection probability was associated with clinical inspection of poultry in the area surrounding infected flocks (7.6%; 95% confidence interval [CI], 1.4%-18.9%) and active culling during depopulation (6.2%; 95% CI, 3.7%-9.6%). Low probabilities were estimated for management of biosecurity (0.0%; 95% CI, 0.0%-1.0%) and cleaning assistance during depopulation (0.0%; 95% CI, 0.0%-9.2%). No significant association was observed between the probability of infection and the exposure variables.

Geographically weighted poisson regression semiparametric on modeling of the number of tuberculosis cases (Case study: Bandung city)

NASA Astrophysics Data System (ADS)

Octavianty, Toharudin, Toni; Jaya, I. G. N. Mindra

2017-03-01

Tuberculosis (TB) is a disease caused by a bacterium, called Mycobacterium tuberculosis, which typically attacks the lungs but can also affect the kidney, spine, and brain (Centers for Disease Control and Prevention). Indonesia had the largest number of TB cases after India (Global Tuberculosis Report 2015 by WHO). The distribution of Mycobacterium tuberculosis genotypes in Indonesia showed the high genetic diversity and tended to vary by geographic regions. For instance, in Bandung city, the prevalence rate of TB morbidity is quite high. A number of TB patients belong to the counted data. To determine the factors that significantly influence the number of tuberculosis patients in each location of the observations can be used statistical analysis tool that is Geographically Weighted Poisson Regression Semiparametric (GWPRS). GWPRS is an extension of the Poisson regression and GWPR that is influenced by geographical factors, and there is also variables that influence globally and locally. Using the TB Data in Bandung city (in 2015), the results show that the global and local variables that influence the number of tuberculosis patients in every sub-district.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA study.

PubMed

Sokka, Tuulikki; Kautiainen, Hannu; Pincus, Theodore; Verstappen, Suzanne M M; Aggarwal, Amita; Alten, Rieke; Andersone, Daina; Badsha, Humeira; Baecklund, Eva; Belmonte, Miguel; Craig-Müller, Jürgen; da Mota, Licia Maria Henrique; Dimic, Alexander; Fathi, Nihal A; Ferraccioli, Gianfranco; Fukuda, Wataru; Géher, Pál; Gogus, Feride; Hajjaj-Hassouni, Najia; Hamoud, Hisham; Haugeberg, Glenn; Henrohn, Dan; Horslev-Petersen, Kim; Ionescu, Ruxandra; Karateew, Dmitry; Kuuse, Reet; Laurindo, Ieda Maria Magalhaes; Lazovskis, Juris; Luukkainen, Reijo; Mofti, Ayman; Murphy, Eithne; Nakajima, Ayako; Oyoo, Omondi; Pandya, Sapan C; Pohl, Christof; Predeteanu, Denisa; Rexhepi, Mjellma; Rexhepi, Sylejman; Sharma, Banwari; Shono, Eisuke; Sibilia, Jean; Sierakowski, Stanislaw; Skopouli, Fotini N; Stropuviene, Sigita; Toloza, Sergio; Valter, Ivo; Woolf, Anthony; Yamanaka, Hisashi

2010-01-01

Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.

Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study

PubMed Central

2010-01-01

Introduction Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. Methods The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. Results At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score. Conclusions Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA. PMID:20226018

Cardiopulmonary Resuscitation in Infants and Children With Cardiac Disease: A Scientific Statement From the American Heart Association.

PubMed

Marino, Bradley S; Tabbutt, Sarah; MacLaren, Graeme; Hazinski, Mary Fran; Adatia, Ian; Atkins, Dianne L; Checchia, Paul A; DeCaen, Allan; Fink, Ericka L; Hoffman, George M; Jefferies, John L; Kleinman, Monica; Krawczeski, Catherine D; Licht, Daniel J; Macrae, Duncan; Ravishankar, Chitra; Samson, Ricardo A; Thiagarajan, Ravi R; Toms, Rune; Tweddell, James; Laussen, Peter C

2018-05-29

Cardiac arrest occurs at a higher rate in children with heart disease than in healthy children. Pediatric basic life support and advanced life support guidelines focus on delivering high-quality resuscitation in children with normal hearts. The complexity and variability in pediatric heart disease pose unique challenges during resuscitation. A writing group appointed by the American Heart Association reviewed the literature addressing resuscitation in children with heart disease. MEDLINE and Google Scholar databases were searched from 1966 to 2015, cross-referencing pediatric heart disease with pertinent resuscitation search terms. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. The recommendations in this statement concur with the critical components of the 2015 American Heart Association pediatric basic life support and pediatric advanced life support guidelines and are meant to serve as a resuscitation supplement. This statement is meant for caregivers of children with heart disease in the prehospital and in-hospital settings. Understanding the anatomy and physiology of the high-risk pediatric cardiac population will promote early recognition and treatment of decompensation to prevent cardiac arrest, increase survival from cardiac arrest by providing high-quality resuscitations, and improve outcomes with postresuscitation care. © 2018 American Heart Association, Inc.

Environmentally-driven ensemble forecasts of dengue fever

NASA Astrophysics Data System (ADS)

Yamana, T. K.; Shaman, J. L.

2017-12-01

Dengue fever is a mosquito-borne viral disease prevalent in the tropics and subtropics, with an estimated 2.5 billion people at risk of transmission. In many areas where dengue is found, disease transmission is seasonal but prone to high inter-annual variability with occasional severe epidemics. Predicting and preparing for periods of higher than average transmission remains a significant public health challenge. Recently, we developed a framework for forecasting dengue incidence using an dynamical model of disease transmission coupled with observational data of dengue cases using data-assimilation methods. Here, we investigate the use of environmental data to drive the disease transmission model. We produce retrospective forecasts of the timing and severity of dengue outbreaks, and quantify forecast predictive accuracy.

Orthopedic, ophthalmic, and psychiatric diseases primarily affect activity limitation for Japanese males and females: Based on the Comprehensive Survey of Living Conditions.

PubMed

Myojin, Tomoya; Ojima, Toshiyuki; Kikuchi, Keiko; Okada, Eisaku; Shibata, Yosuke; Nakamura, Mieko; Hashimoto, Shuji

2017-02-01

Healthy life expectancy (HLE) is used as one of the primary objectives of fundamental health promotion plans and social development plans. Activity limitation is used to calculate HLE, but little study has been done to identify determinants of activity limitation in order to extend HLE. The purpose of this study is to identify diseases and injuries that commonly lead to activity limitation to prioritize countermeasures against activity limitation. We used anonymous data from the 2007 "Comprehensive Survey of Living Conditions," collected by the Ministry of Health, Labour and Welfare of Japan according to the Statistics Act, Article 36. We used logistic regression analyses and calculated odds ratios (ORs) after adjusting for age and sex. Limitation in daily activities was applied as the dependent variable, and each disease/injury was applied as an independent variable in this analysis. Furthermore, population attributable fractions (PAFs) were calculated. The provided data included 98,789 subjects. We used data for 75,986 valid subjects aged 12 years or older. The following diseases showed high PAF: backache (PAF 13.27%, OR 3.88), arthropathia (PAF 7.61%, OR 4.82), eye and optical diseases (PAF 6.39%, OR 2.01), and depression and other mental diseases (PAF 5.70%, OR 11.55). PAFs of cerebrovascular diseases, hypertension, and diabetes were higher for males than for females; on the other hand, PAFs of orthopedic diseases were higher among females. Our results indicate that orthopedic diseases, ophthalmic diseases, and psychiatric diseases particularly affect activity limitation. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Is Khat (Catha edulis) chewing a risk factor for periodontal diseases? A systematic review.

PubMed

Kalakonda, Butchibabu; Al-Maweri, Sadeq-Ali; Al-Shamiri, Hashem-Motahir; Ijaz, Anum; Gamal, Shukri; Dhaifullah, Esam

2017-10-01

Khat (Catha edulis) chewing is a highly prevalent habit in the Arabian Peninsula and East Africa, and has recently spread to Western countries. The association between khat chewing and oral mucosal lesions is well documented in the literature. However, there is no concrete evidence on the association between khat chewing and periodontal disease. The purpose of this systematic review was to analyze the influence of khat chewing on periodontal health. A literature search of PubMed, Scopus and Web of Sciences databases was carried out to identify relevant articles published from 1990 to May 2017. The inclusion criteria were all clinical studies that assessed the relationship between khat chewing and periodontal disease. The search yielded 122 articles, of which 10 were included in this systematic review. Most of the studies exhibited a positive correlation between khat chewing and periodontal disease. Altogether, the analysis of the current evidence reveals that khat chewing is destructive to the periodontium and enhances the risk of periodontal disease progression. However, due to variability of studies, more longitudinal case-controlled studies are highly warranted to establish a causal relation between khat chewing and periodontal disease. Key words: Khat chewing, periodontal health, periodontal disease, risk factor.

Pulmonary sarcoidosis.

PubMed

Spagnolo, Paolo; Rossi, Giulio; Trisolini, Rocco; Sverzellati, Nicola; Baughman, Robert P; Wells, Athol U

2018-05-01

Sarcoidosis is a granulomatous disease of unknown cause, occurs worldwide and has a highly variable prevalence. The disease is typically dominant in the lungs, although it can affect virtually any organ and is unpredictable in its clinical course. The severity of pulmonary sarcoidosis ranges from incidentally discovered radiographic abnormalities in asymptomatic patients to a chronic progressive disease that is refractory to treatment. Mortality from sarcoidosis appears to have increased in the past three decades, with respiratory failure being the most common cause of sarcoidosis-related death. Pulmonary fibrosis, extensive disease on high-resolution chest CT, impaired lung function, and pulmonary hypertension are well established predictors of poor clinical outcomes. In patients who need systemic therapy to control their disease, corticosteroids are the most commonly used first-line treatment, with antimetabolites generally representing an alternative for patients who are unresponsive to corticosteroids or who cannot tolerate them. Indeed, corticosteroid therapy is associated with toxic effects that correlate with both the cumulative dose and duration of treatment. The scarcity of truly effective therapies and shortage of reliable predictors of the unpredictable development of disease in individual patients greatly contribute to making sarcoidosis such a difficult disease to manage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assessing factors related to waist circumference and obesity: application of a latent variable model.

PubMed

Dalvand, Sahar; Koohpayehzadeh, Jalil; Karimlou, Masoud; Asgari, Fereshteh; Rafei, Ali; Seifi, Behjat; Niksima, Seyed Hassan; Bakhshi, Enayatollah

2015-01-01

Because the use of BMI (Body Mass Index) alone as a measure of adiposity has been criticized, in the present study our aim was to fit a latent variable model to simultaneously examine the factors that affect waist circumference (continuous outcome) and obesity (binary outcome) among Iranian adults. Data included 18,990 Iranian individuals aged 20-65 years that are derived from the third National Survey of Noncommunicable Diseases Risk Factors in Iran. Using latent variable model, we estimated the relation of two correlated responses (waist circumference and obesity) with independent variables including age, gender, PR (Place of Residence), PA (physical activity), smoking status, SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure), CHOL (cholesterol), FBG (Fasting Blood Glucose), diabetes, and FHD (family history of diabetes). All variables were related to both obesity and waist circumference (WC). Older age, female sex, being an urban resident, physical inactivity, nonsmoking, hypertension, hypercholesterolemia, hyperglycemia, diabetes, and having family history of diabetes were significant risk factors that increased WC and obesity. Findings from this study of Iranian adult settings offer more insights into factors associated with high WC and high prevalence of obesity in this population.

The Geomagnetic Field and Correlations with Multiple Sclerosis: A Possible Etiology of Disease

NASA Astrophysics Data System (ADS)

Wade, Brett

Multiple sclerosis (MS) is a complex autoimmune disease that results in a demyelinating process of the central nervous system. It is the most common, progressive, neurological disease affecting young adults, and there is no cure. A curious feature of MS is its distinct global prevalence with high rates of occurrence between 40 and 60 degrees latitude. While genetics may partially explain this phenomenon, studies have shown that the influence of genetics is modest. Many non-genetic variables, such as viruses, vitamin D, smoking, diet, hormones, etc., have been shown to be related to the expression of MS but none of these variables have been determined to be necessarily strong enough to exclude other factors. The geomagnetic field, which is a non-uniform, three dimensional entity which protects all living things from ionizing radiation, is suggested in this research to be related to global MS prevalence. This study hypothesized that either the total field, the vertical field, or the horizontal field strength of the geomagnetic field will be correlated with MS. Using secondary sources of prevalence studies (N=131) and geomagnetic data, the results supported all three hypotheses with the strongest correlation being an inverse relationship between the horizontal field and MS (r = -.607). The explanation for the inverse relationship being most strongly correlated with MS prevalence is explained by the fact that the horizontal aspect of the geomagnetic field has a protective effect from incoming cosmic radiation. Chronic exposure to high levels of background radiation can have deleterious health effects. This research suggests that living in areas of a weak horizontal field increases a person's exposure to ionizing radiation and therefore increases the risk for developing MS. While it was not the intention of this research, it became clear that an explanation which explained the results of this research and also attempted to unify the mechanisms of all non-genetic variables was prudent. A Unified Theory of MS Disease Expression is presented in this research.

Interannual Variability of Human Plague Occurrence in the Western United States Explained by Tropical and North Pacific Ocean Climate Variability

PubMed Central

Ari, Tamara Ben; Gershunov, Alexander; Tristan, Rouyer; Cazelles, Bernard; Gage, Kenneth; Stenseth, Nils C.

2010-01-01

Plague is a vector-borne, highly virulent zoonotic disease caused by the bacterium Yersinia pestis. It persists in nature through transmission between its hosts (wild rodents) and vectors (fleas). During epizootics, the disease expands and spills over to other host species such as humans living in or close to affected areas. Here, we investigate the effect of large-scale climate variability on the dynamics of human plague in the western United States using a 56-year time series of plague reports (1950–2005). We found that El Niño Southern Oscillation and Pacific Decadal Oscillation in combination affect the dynamics of human plague over the western United States. The underlying mechanism could involve changes in precipitation and temperatures that impact both hosts and vectors. It is suggested that snow also may play a key role, possibly through its effects on summer soil moisture, which is known to be instrumental for flea survival and development and sustained growth of vegetation for rodents. PMID:20810830

Self-perceived health among 'quilombolas' in northern Minas Gerais, Brazil.

PubMed

Oliveira, Stéphany Ketllin Mendes; Pereira, Mayane Moura; Guimarães, Luiz Sena; Caldeira, Antônio Prates

2015-09-01

Over a century has passed since slavery was abolished in Brazil, yet quilombola communities remain socially vulnerable, especially when it comes to health. The goal of this study was to understand self-perceived health (SPH) in quilombola communities in Northern Minas Gerais, and the factors associated with their negative -perceived their own health. A household survey of a representative sample of quilombola communities in the study region. Validated tools were used to gather data about SPH, socioeconomic conditions, demographics, lifestyle and self-referred morbidity. Following a bivariate analysis, we proceeded to conduct a hierarchical logistics regression analysis. The prevalence of negative SPH was 46.0%. The following variables were statistically associated with negative SPH: age and years of schooling as distal variables, and high blood pressure, diabetes, arthritis, depression and back problems as proximal variables. SPH is associated with demographic and socioeconomic dimensions, and in particular with self-referred morbidity. The concept of health among the quilombola communities included in this study seems to be intimately linked to the absence of disease, especially chronic disease.

[Indicators and factors of influence on the long-term follow-up of psychogenic diseases--a comparison of extreme groups].

PubMed

Franz, M; Schellberg, D; Schepank, H

1995-02-01

The present investigation aimed at the identification of possible indicators of course, predictors, and etiologically relevant factors of psychogenic diseases. According to their complaints a sample of probands suffering from psychogenic impairment of medium degree (n = 240) was chosen out of a representative sample of an urban adult population (n = 528). This procedure should ensure a relatively high intraindividual variance of course of the criterion, since a sufficient variability of course seems improbable with chronic and severe psychogenic impaired or stabile healthy probands. Within 10 years the sample was investigated three times by psychodynamically trained physicians and psychologists. By means of cluster analysis the sample was subdivided in different types of course of psychogenic impairment. Both extreme types of course-the probands who showed the most positive and the most negative spontaneous longterm course-were investigated univariately and by means of a multivariate discriminant analysis with regard to potentially course determining variables. It became obvious that personality variables and conditions of early childhood considerably influenced the spontaneous longterm course of psychogenic impairment.

A brief review and clinical application of heart rate variability biofeedback in sports, exercise, and rehabilitation medicine.

PubMed

Prinsloo, Gabriell E; Rauch, H G Laurie; Derman, Wayne E

2014-05-01

An important component of the effective management of chronic noncommunicable disease is the assessment and management of psychosocial stress. The measurement and modulation of heart rate variability (HRV) may be valuable in this regard. To describe the measurement and physiological control of HRV; to describe the impact of psychosocial stress on cardiovascular disease, metabolic syndrome, and chronic respiratory disease, and the relationship between these diseases and changes in HRV; and to describe the influence of biofeedback and exercise on HRV and the use of HRV biofeedback in the management of chronic disease. The PubMed, Medline, and Embase databases were searched (up to August 2013). Additional articles were obtained from the reference lists of relevant articles and reviews. Articles were individually selected for further review based on the quality and focus of the study, and the population studied. Heart rate variability is reduced in stress and in many chronic diseases, and may even predict the development and prognosis of some diseases. Heart rate variability can be increased with both exercise and biofeedback. Although the research on the effect of exercise is conflicting, there is evidence that aerobic training may increase HRV and cardiac vagal tone both in healthy individuals and in patients with disease. Heart rate variability biofeedback is also an effective method of increasing HRV and cardiac vagal tone, and has been shown to decrease stress and reduce the morbidity and mortality of disease. The assessment and management of psychosocial stress is a challenging but important component of effective comprehensive lifestyle interventions for the management of noncommunicable disease. It is, therefore, important for the sports and exercise physician to have an understanding of the therapeutic use of HRV modulation, both in the reduction of stress and in the management of chronic disease.

Variability in adherence to clinical practice guidelines and recommendations in COPD outpatients: a multi-level, cross-sectional analysis of the EPOCONSUL study.

PubMed

Calle Rubio, Myriam; López-Campos, José Luis; Soler-Cataluña, Juan J; Alcázar Navarrete, Bernardino; Soriano, Joan B; Rodríguez González-Moro, José Miguel; Fuentes Ferrer, Manuel E; Rodríguez Hermosa, Juan Luis

2017-12-02

Clinical audits have reported considerable variability in COPD medical care and frequent inconsistencies with recommendations. The objectives of this study were to identify factors associated with a better adherence to clinical practice guidelines and to explore determinants of this variability at the the hospital level. EPOCONSUL is a Spanish nationwide clinical audit that evaluates the outpatient management of COPD. Multilevel logistic regression with two levels was performed to assess the relationships between individual and disease-related factors, as well as hospital characteristics. A total of 4508 clinical records of COPD patients from 59 Spanish hospitals were evaluated. High variability was observed among hospitals in terms of medical care. Some of the patient's characteristics (airflow obstruction, degree of dyspnea, exacerbation risk, presence of comorbidities), the hospital factors (size and respiratory nurses available) and treatment at a specialized COPD outpatient clinic were identified as factors associated with a better adherence to recommendations, although this only explains a small proportion of the total variance. To be treated at a specialized COPD outpatient clinic and some intrinsic patient characteristics were factors associated with a better adherence to guideline recommendations, although these variables were only explaining part of the high variability observed among hospitals in terms of COPD medical care.

Seronegative celiac disease: Shedding light on an obscure clinical entity.

PubMed

Volta, Umberto; Caio, Giacomo; Boschetti, Elisa; Giancola, Fiorella; Rhoden, Kerry J; Ruggeri, Eugenio; Paterini, Paola; De Giorgio, Roberto

2016-09-01

Although serological tests are useful for identifying celiac disease, it is well established that a minority of celiacs are seronegative. To define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy. Starting from 810 celiac disease diagnoses, seronegative patients were retrospectively characterized for clinical, histological and laboratory findings. Of the 810 patients, fourteen fulfilled the diagnostic criteria for seronegative celiac disease based on antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Compared to seropositive, seronegative celiac disease showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype (i.e., malabsorption), autoimmune disorders and severe villous atrophy. The most frequent diagnosis in the 31 cases with seronegative flat mucosa was celiac disease (45%), whereas other diagnoses were Giardiasis (20%), common variable immunodeficiency (16%) and autoimmune enteropathy (10%). Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Patterns of oral disease in adults with chronic kidney disease treated with hemodialysis.

PubMed

Palmer, Suetonia C; Ruospo, Marinella; Wong, Germaine; Craig, Jonathan C; Petruzzi, Massimo; De Benedittis, Michele; Ford, Pauline; Johnson, David W; Tonelli, Marcello; Natale, Patrizia; Saglimbene, Valeria; Pellegrini, Fabio; Celia, Eduardo; Gelfman, Ruben; Leal, Miguel R; Torok, Marietta; Stroumza, Paul; Frantzen, Luc; Bednarek-Skublewska, Anna; Dulawa, Jan; Del Castillo, Domingo; Bernat, Amparo G; Hegbrant, Jorgen; Wollheim, Charlotta; Schon, Staffan; Gargano, Letizia; Bots, Casper P; Strippoli, Giovanni F M

2016-10-01

Oral disease is a potentially treatable determinant of mortality and quality of life. No comprehensive multinational study to quantify oral disease burden and to identify candidate preventative strategies has been performed in the dialysis setting. The ORAL disease in hemoDialysis (ORALD) study was a prospective study in adults treated with hemodialysis in Europe (France, Hungary, Italy, Poland, Portugal and Spain) and Argentina. Oral disease was assessed using standardized WHO methods. Participants self-reported oral health practices and symptoms. Sociodemographic and clinical factors associated with oral diseases were determined and assessed within nation states. Of 4726 eligible adults, 4205 (88.9%) participated. Overall, 20.6% were edentulous [95% confidence interval (CI), 19.4-21.8]. Participants had on average 22 (95% CI 21.7-22.2) decayed, missing or filled teeth, while moderate to severe periodontitis affected 40.6% (95% CI 38.9-42.3). Oral disease patterns varied markedly across countries, independent of participant demographics, comorbidity and health practices. Participants in Spain, Poland, Italy and Hungary had the highest mean adjusted odds of edentulousness (2.31, 1.90, 1.90 and 1.54, respectively), while those in Poland, Hungary, Spain and Argentina had the highest odds of ≥14 decayed, missing or filled teeth (23.2, 12.5, 8.14 and 5.23, respectively). Compared with Argentina, adjusted odds ratios for periodontitis were 58.8, 58.3, 27.7, 12.1 and 6.30 for Portugal, Italy, Hungary, France and Poland, respectively. National levels of tobacco consumption, diabetes and child poverty were associated with edentulousness within countries. Oral disease in adults on hemodialysis is very common, frequently severe and highly variable among countries, with much of the variability unexplained by participant characteristics or healthcare. Given the national variation and high burden of disease, strategies to improve oral health in hemodialysis patients will require implementation at a country level rather than at the level of individuals. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation

PubMed Central

Dopazo, Joaquín; Amadoz, Alicia; Bleda, Marta; Garcia-Alonso, Luz; Alemán, Alejandro; García-García, Francisco; Rodriguez, Juan A.; Daub, Josephine T.; Muntané, Gerard; Rueda, Antonio; Vela-Boza, Alicia; López-Domingo, Francisco J.; Florido, Javier P.; Arce, Pablo; Ruiz-Ferrer, Macarena; Méndez-Vidal, Cristina; Arnold, Todd E.; Spleiss, Olivia; Alvarez-Tejado, Miguel; Navarro, Arcadi; Bhattacharya, Shomi S.; Borrego, Salud; Santoyo-López, Javier; Antiñolo, Guillermo

2016-01-01

Recent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalog of local variability motivated the whole-exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one-third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including ∼10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes, and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies to distinguish real disease associations from population-specific polymorphisms. PMID:26764160

Historical Compilation and Georeferencing of Dengue and Chikungunya outbreak data for Disease Modeling

USDA-ARS?s Scientific Manuscript database

The risk of vector-borne disease spread is increasing due to significant changes and variability in the global climate and increasing global travel and trade. Understanding the relationships between climate variability and disease outbreak patterns are critical to the design and construction of pred...

Effect of meteorological variables on the incidence of hand, foot, and mouth disease in children: a time-series analysis in Guangzhou, China.

PubMed

Huang, Yong; Deng, Te; Yu, Shicheng; Gu, Jing; Huang, Cunrui; Xiao, Gexin; Hao, Yuantao

2013-03-13

Over the last decade, major outbreaks of hand, foot, and mouth disease (HFMD) have been reported in Asian countries, resulting in thousands of deaths among children. However, less is known regarding the effect of meteorological variables on the incidence of HFMD in children. This study aims at quantifying the relationship between meteorological variables and the incidence of HFMD among children in Guangzhou, China. The association between weekly HFMD cases in children aged <15 years and meteorological variables in Guangzhou from 2008 to 2011 were analyzed using the generalized additive model (GAM) and time-series method, after controlling for long-term trend and seasonality, holiday effects, influenza period and delayed effects. Temperature and relative humidity with one week lag were significantly associated with HFMD infection among children. We found that a 1°C increase in temperature led to an increase of 1.86% (95% CI: 0.92, 2.81%) in the weekly number of cases in the 0-14 years age group. A one percent increase in relative humidity may lead to an increase of 1.42% (95% CI: 0.97, 1.87%) in the weekly number of cases in the 0-14 years age group. This study provides quantitative evidence that the incidence of HFMD in children was associated with high average temperature and high relative humidity. The one-week delay in the effects of temperature and relative humidity on HFMD is consistent with the enterovirus incubation period and the potential time lag between onset of children's sickness and parental awareness and response.

Favorable Local Control From Consolidative Radiation Therapy in High-Risk Neuroblastoma Despite Gross Residual Disease, Positive Margins, or Nodal Involvement

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

Ferris, Matthew J., E-mail: mjferri@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; Danish, Hasan

Purpose: To report the influence of radiation therapy (RT) dose and surgical pathology variables on disease control and overall survival (OS) in patients treated for high-risk neuroblastoma at a single institution. Methods and Materials: We conducted a retrospective study of 67 high-risk neuroblastoma patients who received RT as part of definitive management from January 2003 until May 2014. Results: At a median follow-up of 4.5 years, 26 patients (38.8%) failed distantly; 4 of these patients also failed locally. One patient progressed locally without distant failure. Local control was 92.5%, and total disease control was 59.5%. No benefit was demonstrated for RT doses over 21.6 Gymore » with respect to local relapse–free survival (P=.55), disease-free survival (P=.22), or OS (P=.72). With respect to local relapse–free survival, disease-free survival, and OS, no disadvantage was seen for positive lymph nodes on surgical pathology, positive surgical margins, or gross residual disease. Of the patients with gross residual disease, 75% (6 of 8) went on to have no evidence of disease at time of last follow-up, and the 2 patients who failed did so distantly. Conclusions: Patients with high-risk neuroblastoma in this series maintained excellent local control, with no benefit demonstrated for radiation doses over 21.6 Gy, and no disadvantage demonstrated for gross residual disease after surgery, positive surgical margins, or pathologic lymph node positivity. Though the limitations of a retrospective review for an uncommon disease must be kept in mind, with small numbers in some of the subgroups, it seems that dose escalation should be considered only in exceptional circumstances.« less

A method for screening climate change-sensitive infectious diseases.

PubMed

Wang, Yunjing; Rao, Yuhan; Wu, Xiaoxu; Zhao, Hainan; Chen, Jin

2015-01-14

Climate change is a significant and emerging threat to human health, especially where infectious diseases are involved. Because of the complex interactions between climate variables and infectious disease components (i.e., pathogen, host and transmission environment), systematically and quantitatively screening for infectious diseases that are sensitive to climate change is still a challenge. To address this challenge, we propose a new statistical indicator, Relative Sensitivity, to identify the difference between the sensitivity of the infectious disease to climate variables for two different climate statuses (i.e., historical climate and present climate) in non-exposure and exposure groups. The case study in Anhui Province, China has demonstrated the effectiveness of this Relative Sensitivity indicator. The application results indicate significant sensitivity of many epidemic infectious diseases to climate change in the form of changing climatic variables, such as temperature, precipitation and absolute humidity. As novel evidence, this research shows that absolute humidity has a critical influence on many observed infectious diseases in Anhui Province, including dysentery, hand, foot and mouth disease, hepatitis A, hemorrhagic fever, typhoid fever, malaria, meningitis, influenza and schistosomiasis. Moreover, some infectious diseases are more sensitive to climate change in rural areas than in urban areas. This insight provides guidance for future health inputs that consider spatial variability in response to climate change.

A Method for Screening Climate Change-Sensitive Infectious Diseases

PubMed Central

Wang, Yunjing; Rao, Yuhan; Wu, Xiaoxu; Zhao, Hainan; Chen, Jin

2015-01-01

Climate change is a significant and emerging threat to human health, especially where infectious diseases are involved. Because of the complex interactions between climate variables and infectious disease components (i.e., pathogen, host and transmission environment), systematically and quantitatively screening for infectious diseases that are sensitive to climate change is still a challenge. To address this challenge, we propose a new statistical indicator, Relative Sensitivity, to identify the difference between the sensitivity of the infectious disease to climate variables for two different climate statuses (i.e., historical climate and present climate) in non-exposure and exposure groups. The case study in Anhui Province, China has demonstrated the effectiveness of this Relative Sensitivity indicator. The application results indicate significant sensitivity of many epidemic infectious diseases to climate change in the form of changing climatic variables, such as temperature, precipitation and absolute humidity. As novel evidence, this research shows that absolute humidity has a critical influence on many observed infectious diseases in Anhui Province, including dysentery, hand, foot and mouth disease, hepatitis A, hemorrhagic fever, typhoid fever, malaria, meningitis, influenza and schistosomiasis. Moreover, some infectious diseases are more sensitive to climate change in rural areas than in urban areas. This insight provides guidance for future health inputs that consider spatial variability in response to climate change. PMID:25594780

Taste phenotype associates with cardiovascular disease risk factors via diet quality in multivariate modeling.

PubMed

Sharafi, Mastaneh; Rawal, Shristi; Fernandez, Maria Luz; Huedo-Medina, Tania B; Duffy, Valerie B

2018-05-08

Sensations from foods and beverages drive dietary choices, which in turn, affect risk of diet-related diseases. Perception of these sensation varies with environmental and genetic influences. This observational study aimed to examine associations between chemosensory phenotype, diet and cardiovascular disease (CVD) risk. Reportedly healthy women (n = 110, average age 45 ± 9 years) participated in laboratory-based measures of chemosensory phenotype (taste and smell function, propylthiouracil (PROP) bitterness) and CVD risk factors (waist circumference, blood pressure, serum lipids). Diet variables included preference and intake of sweet/high-fat foods, dietary restraint, and diet quality based on reported preference (Healthy Eating Preference Index-HEPI) and intake (Healthy Eating Index-HEI). We found that females who reported high preference yet low consumption of sweet/high-fat foods had the highest dietary restraint and depressed quinine taste function. PROP nontasters were more likely to report lower diet quality; PROP supertasters more likely to consume but not like a healthy diet. Multivariate structural models were fitted to identify predictors of CVD risk factors. Reliable latent taste (quinine taste function, PROP tasting) and smell (odor intensity) variables were identified, with taste explaining more variance in the CVD risk factors. Lower bitter taste perception was associated with elevated risk. In multivariate models, the HEPI completely mediated the taste-adiposity and taste-HDL associations and partially mediated the taste-triglyceride or taste-systolic blood pressure associations. The taste-LDL pathway was significant and direct. The HEI could not replace HEPI in adequate models. However, using a latent diet quality variable with HEPI and HEI, increased the strength of association between diet quality and adiposity or CVD risk factors. In conclusion, bitter taste phenotype was associated with CVD risk factors via diet quality, particularly when assessed by level of food liking/disliking. Copyright © 2018 Elsevier Inc. All rights reserved.

Bayesian dynamic modeling of time series of dengue disease case counts

PubMed Central

López-Quílez, Antonio; Torres-Prieto, Alexander

2017-01-01

The aim of this study is to model the association between weekly time series of dengue case counts and meteorological variables, in a high-incidence city of Colombia, applying Bayesian hierarchical dynamic generalized linear models over the period January 2008 to August 2015. Additionally, we evaluate the model’s short-term performance for predicting dengue cases. The methodology shows dynamic Poisson log link models including constant or time-varying coefficients for the meteorological variables. Calendar effects were modeled using constant or first- or second-order random walk time-varying coefficients. The meteorological variables were modeled using constant coefficients and first-order random walk time-varying coefficients. We applied Markov Chain Monte Carlo simulations for parameter estimation, and deviance information criterion statistic (DIC) for model selection. We assessed the short-term predictive performance of the selected final model, at several time points within the study period using the mean absolute percentage error. The results showed the best model including first-order random walk time-varying coefficients for calendar trend and first-order random walk time-varying coefficients for the meteorological variables. Besides the computational challenges, interpreting the results implies a complete analysis of the time series of dengue with respect to the parameter estimates of the meteorological effects. We found small values of the mean absolute percentage errors at one or two weeks out-of-sample predictions for most prediction points, associated with low volatility periods in the dengue counts. We discuss the advantages and limitations of the dynamic Poisson models for studying the association between time series of dengue disease and meteorological variables. The key conclusion of the study is that dynamic Poisson models account for the dynamic nature of the variables involved in the modeling of time series of dengue disease, producing useful models for decision-making in public health. PMID:28671941

Longitudinal follow-up of fibrosing interstitial pneumonia: relationship between physiologic testing, computed tomography changes, and survival rate.

PubMed

Hwang, Jeong-Hwa; Misumi, Shigeki; Curran-Everett, Douglas; Brown, Kevin K; Sahin, Hakan; Lynch, David A

2011-08-01

The aim of this study was to evaluate the prognostic implications of computed tomography (CT) and physiologic variables at baseline and on sequential evaluation in patients with fibrosing interstitial pneumonia. We identified 72 patients with fibrosing interstitial pneumonia (42 with idiopathic disease, 30 with collagen vascular disease). Pulmonary function tests and CT were performed at the time of diagnosis and at a median follow-up of 12 months, respectively. Two chest radiologists scored the extent of specific abnormalities and overall disease on baseline and follow-up CT. Rate of survival was estimated using the Kaplan-Meier method. Three Cox proportional hazards models were constructed to evaluate the relationship between CT and physiologic variables and rate of survival: model 1 included only baseline variables, model 2 included only serial change variables, and model 3 included both baseline and serial change variables. On follow-up CT, the extent of mixed ground-glass and reticular opacities (P<0.001), pure reticular opacity (P=0.04), honeycombing (P=0.02), and overall extent of disease (P<0.001) was increased in the idiopathic group, whereas these variables remained unchanged in the collagen vascular disease group. Patients with idiopathic disease had a shorter rate of survival than those with collagen vascular disease (P=0.03). In model 1, the extent of honeycombing on baseline CT was the only independent predictor of mortality (P=0.02). In model 2, progression in honeycombing was the only predictor of mortality (P=0.005). In model 3, baseline extent of honeycombing and progression of honeycombing were the only independent predictors of mortality (P=0.001 and 0.002, respectively). Neither baseline nor serial change physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival. The extent of honeycombing at baseline and its progression on follow-up CT are important determinants of rate of survival in patients with fibrosing interstitial pneumonia.

Influence of Pulmonary Nodules on Chest Computed Tomography and Risk of Recurrence in Stage IV Wilms Tumor

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

Kirkland, Robert S.; Nanda, Ronica H., E-mail: rhazari@emory.edu; Alazraki, Adina

Purpose: Chest computed tomography (CT) is currently accepted as the main modality for initial disease staging and response assessment in Wilms tumor (WT). However, there is great variability in the number and size of lung metastases at the time of diagnosis and after induction chemotherapy. There is a lack of clinical evidence as to how this variability in tumor burden affects choice of therapy and disease outcome. This study sought to evaluate a previously proposed lung metastases risk stratification system based on CT findings and clinical outcomes in stage IV WT patients. Methods and Materials: Thirty-five pediatric patients with amore » diagnosis of stage IV WT with evaluable pre- and postdiagnosis CT scans between 1997 and 2012 were included in the analysis. Patients were divided into low-, intermediate-, and high-risk categories based on the size and number of pulmonary metastases before and after 6 weeks of chemotherapy. Association of the lung risk groups with lung recurrence-free survival and overall survival at each time point was analyzed with relevant covariates. Results: Risk group distribution both at diagnosis and after induction chemotherapy was not influenced by tumor histology. Initial risk grouping suggested an association with disease-free survival at 5 years (P=.074); however, the most significant correlation was with postinduction chemotherapy disease status (P=.027). In patients with an intermediate or high burden of disease after 6 weeks of chemotherapy, despite receiving whole-lung and boost irradiation, survival outcomes were poorer. Conclusions: Pulmonary tumor burden in stage IV WT on chest CT can predict disease outcome. Patients with intermediate- or low-risk disease, especially after induction therapy, have a higher risk for recurrence. After prospective validation, this method may become a valuable tool in adaptation of therapy to improve outcome.« less

Impact of anxiety, apathy and reduced functional autonomy on perceived quality of life in Parkinson's disease.

PubMed

D'Iorio, Alfonsina; Vitale, Carmine; Piscopo, Fausta; Baiano, Chiara; Falanga, Anna Paola; Longo, Katia; Amboni, Marianna; Barone, Paolo; Santangelo, Gabriella

2017-10-01

Parkinson's disease (PD) is characterized by a wide spectrum of non-motor symptoms that may impact negatively on the activities of the patient's daily life and reduce Health-related quality of life (HRQoL). The present study explored the impact of specific non-motor symptoms on the HRQoL in PD. Eighty-four outpatients underwent the Montreal Cognitive Assessment (MoCA) assessing global functioning and several questionnaires to assess depression, apathy, impulse control disorders (ICD), anxiety, anhedonia and functional impact of cognitive impairment. The perceived QoL was assessed by Parkinson's Disease Questionnaire (PDQ-8). The PD sample was divided into patients with high and low HRQoL around the median of PDQ-8 and compared on clinical features, cognitive and neuropsychiatric variables. A linear regression analysis, in which the global functioning, apathy, depression, anxiety, anhedonia, ICD and the functional autonomy scores were entered as independent variables and PDQ-8 score as dependent variable, was applied. Patients with lower HRQoL were more depressed, apathetic, anxious and showed more severe reduction of functional autonomy and global functioning than patients with high HRQoL. The regression analysis revealed that higher level of anxiety, executive apathy and more reduced functional autonomy were significantly associated with higher score on PDQ-8. The finding indicated that anxiety, apathy associated with impaired planning, attention and organization (i.e., executive apathy evaluated by the Dimensional Apathy Scale) and reduced functional autonomy contribute significantly to reduce the HRQoL in PD. Therefore, early identification and management of these neuropsychiatric symptoms should be relevant to preserve HRQoL in PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hotspot detection using space-time scan statistics on children under five years of age in Depok

NASA Astrophysics Data System (ADS)

Verdiana, Miranti; Widyaningsih, Yekti

2017-03-01

Some problems that affect the health level in Depok is the high malnutrition rates from year to year and the more spread infectious and non-communicable diseases in some areas. Children under five years old is a vulnerable part of population to get the malnutrition and diseases. Based on this reason, it is important to observe the location and time, where and when, malnutrition in Depok happened in high intensity. To obtain the location and time of the hotspots of malnutrition and diseases that attack children under five years old, space-time scan statistics method can be used. Space-time scan statistic is a hotspot detection method, where the area and time of information and time are taken into account simultaneously in detecting the hotspots. This method detects a hotspot with a cylindrical scanning window: the cylindrical pedestal describes the area, and the height of cylinder describe the time. Cylinders formed is a hotspot candidate that may occur, which require testing of hypotheses, whether a cylinder can be summed up as a hotspot. Hotspot detection in this study carried out by forming a combination of several variables. Some combination of variables provides hotspot detection results that tend to be the same, so as to form groups (clusters). In the case of infant health level in Depok city, Beji health care center region in 2011-2012 is a hotspot. According to the combination of the variables used in the detection of hotspots, Beji health care center is most frequently as a hotspot. Hopefully the local government can take the right policy to improve the health level of children under five in the city of Depok.

Imaging and histologic prognostic factors in triple-negative breast cancer and carcinoma in situ as a prognostic factor.

PubMed

Sebastián Sebastián, C; García Mur, C; Cruz Ciria, S; Rosero Cuesta, D S; Gros Bañeres, B

2016-01-01

To analyze what factors in magnetic resonance imaging (MRI) and histological study of triple-negative breast cancers are related to tumor recurrence and to shorter disease-free survival. To analyze survival and recurrence in function of the presence of an in situ component. This was a retrospective study of MRI staging examinations in 122 women with triple-negative breast cancer done from 2007 through 2014. In the MRI, we evaluated morphological variables (size, margins, morphology, internal signal in T2-weighted sequences) and dynamic variables (perfusion and diffusion). In the histological study, we evaluated Ki67, p53, CK5/6, nuclear grade, and Scarff-Bloom grade, as well as the presence of an in situ component and tumor grade (high grade or not high grade). We compared the variables between patients with tumor recurrence and those without, and we conducted a survival analysis. Non-nodular enhancement was more common in patients with tumor recurrence (p=0.038) and was associated with shorter disease-free survival (p=0.023). Neither diffusion restriction (p=0.079) nor ki67 (p=0.052) was associated with a worse prognosis. An in situ component was detected in 44% of triple-negative tumors, and a greater proportion of patients in the group with tumor recurrence had an in situ component; however, the presence of an in situ component was not associated with shorter survival (p = 0.185). Non-nodular enhancement was associated with a worse prognosis. Diffusion restriction, ki67, and the presence of an in situ component were not associated with shorter disease-free survival. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Pharmacokinetics and relative bioavailability of clofazimine in relation to food, orange juice and antacid.

PubMed

Nix, D E David E; Adam, R D Rodney D; Auclair, Barbara; Krueger, T S Todd S; Godo, P G Paul G; Peloquin, C A Charles A

2004-01-01

Clofazimine is potentially useful for the treatment of disease due to multidrug resistant Mycobacterium tuberculosis, as well as leprosy and certain chronic skin diseases. Its pharmacokinetics have been incompletely characterized. This study was conducted to explore issues relating to bioavailability in the presence of food, orange juice, and antacid. A 5 drug regimen consisting of clofazimine, cycloserine, ethionamide, para-aminosalicyclic acid, and pyridoxime was administered to healthy subjects four times using a four period cross-over design with two weeks washout between treatments. Subjects also received orange juice, a high fat meal, aluminum/magnesium antacid, or only water in random order with the drug regimen. The pharmacokinetics of clofazimine were assessed using individual- and population-based methods and relative bioavailability compared to fasting administration was determined. Clofazimine exhibited a sometimes prolonged and variable lag-time and considerable variability in plasma concentrations. From the population analysis (one-compartment model), the mean oral clearance was 76.7 l/h (CV=74.2%) and mean apparent volume of distribution was 1470 l (CV=36.3%). The first-order absorption rate constant ranged from 0.716 to 1.33 h(-1) (pooled CV=61.7%). Residual (proportional) error was 49.1%. Estimates of bioavailability compared to fasting administration were 145% (90% CI, 107-183%) for administration with high fat food, 82.0% (63.2-101%) for administration with orange juice, and 78.5% (55.1-102%) for administration with antacid. Administration of clofazimine with a high fat meal provides the greatest bioavailability, however, bioavailability is associated with high inter- and intra-subject variability. Both orange juice and aluminum-magnesium antacid produced a reduction in mean bioavailability of clofazimine.

Mapping of the antigenic determinants of the T. cruzi kinetoplastid membrane protein-11. Identification of a linear epitope specifically recognized by human Chagasic sera.

PubMed

Thomas, M C; Longobardo, M V; Carmelo, E; Marañón, C; Planelles, L; Patarroyo, M E; Alonso, C; López, M C

2001-03-01

The high variability among strains and isolates of Trypanosoma cruzi and the existence of shared antigenic determinants with other pathogens, particularly with members of the Leishmania genus make difficult the specific diagnosis of Chagas' disease. The data reported in this paper show that the T. cruzi KMP11 protein is an immunodominant antigen highly recognized by the sera from chagasic and leishmaniasis patients. By the use of amino- and carboxyl-terminal truncated KMP11 recombinant proteins and synthetic peptides, evidence is provided that while the sera from chagasic patients recognize linear peptides the sera from patients with visceral leishmaniasis must be predominantly directed against conformational epitopes. We found that a particular linear determinant, located in the carboxyl-terminal region of the protein, is recognized with high specificity and sensitivity only by sera from Chagas' disease patients, suggesting it could be a good candidate for differential serodiagnosis of Chagas' disease.

Mapping of the antigenic determinants of the T. cruzi kinetoplastid membrane protein-11. Identification of a linear epitope specifically recognized by human Chagasic sera

PubMed Central

Thomas, M C; Longobardo, M V; Carmelo, E; Marañón, C; Planelles, L; Patarroyo, M E; Alonso, C; López, M C

2001-01-01

The high variability among strains and isolates of Trypanosoma cruzi and the existence of shared antigenic determinants with other pathogens, particularly with members of the Leishmania genus make difficult the specific diagnosis of Chagas' disease. The data reported in this paper show that the T. cruzi KMP11 protein is an immunodominant antigen highly recognized by the sera from chagasic and leishmaniasis patients. By the use of amino- and carboxyl-terminal truncated KMP11 recombinant proteins and synthetic peptides, evidence is provided that while the sera from chagasic patients recognize linear peptides the sera from patients with visceral leishmaniasis must be predominantly directed against conformational epitopes. We found that a particular linear determinant, located in the carboxyl-terminal region of the protein, is recognized with high specificity and sensitivity only by sera from Chagas' disease patients, suggesting it could be a good candidate for differential serodiagnosis of Chagas' disease. PMID:11298135

The impact of glycaemic variability on wound healing in the diabetic foot - A retrospective study of new ulcers presenting to a specialist multidisciplinary foot clinic.

PubMed

Dhatariya, Ketan K; Li Ping Wah-Pun Sin, Edwin; Cheng, Joyce Oi Suet; Li, Francesca Yan Nok; Yue, Anson Wei Yue; Gooday, Catherine; Nunney, Ian

2018-01-01

Glycaemic variability - the visit-to-visit variation in HbA1c - plays a possible role in the development of micro and macrovascular disease in patients with diabetes. Whether HbA1c variability is a factor determining wound healing in diabetic foot ulcers remains unknown. We aimed to determine whether HbA1c variability is associated with foot ulcer healing time. A retrospective analysis of patients presenting to our specialist multidisciplinary foot clinic between July 2013 and March 2015, with at least three HbA1c measurements within five years of presentation and more than two follow-up reviews. HbA1c variation was measured by magnitude of standard deviation. 629 new referrals were seen between July 2013 and March 2015. Of these, 172 patients had their number of days to healing recorded and sufficient numbers of HbA1c values to determine variability. The overall geometric mean days to heal was 91.1 days (SD 80.8-102.7). In the low HbA1c variability group the geometric mean days to heal was 78.0 days (60.2-101.2) vs 126.9 days (102.0-158.0) in the high Hb1Ac variability group (p = .032). Those with low HbA1c (<58 mmol/mol) and low variability healed faster than those with high HbA1c and high variability (73.5 days [59.5-90.8] vs 111.0 days [92.0-134.0], p = .007). Additionally, our results show that time to healing is more dependent on the mean HbA1c than the variability in HbA1c (p = .007). Our data suggest that there was a significant association between HbA1c variability and healing time in diabetic foot ulcers. Copyright © 2017 Elsevier B.V. All rights reserved.

Do elevated nutrients and organic carbon on Philippine reefs increase the prevalence of coral disease?

NASA Astrophysics Data System (ADS)

Kaczmarsky, L.; Richardson, L. L.

2011-03-01

Characterizations of Philippine coral diseases are very limited. The two most common, ulcerative white spot disease (UWS) and massive Porites growth anomalies (MPGA), target the genus Porites, a dominant reef-building genus. This is the first investigation in the Philippines to detect positive correlations between coral disease, nutrient levels, and organic carbon. A total of 5,843 Porites colonies were examined. Water and sediment samples were collected for analyses of nutrients (total nitrogen and phosphorus) and total organic carbon at 15 sites along a 40.5 km disease gradient, which was previously shown to positively correlate with human population levels. Results suggest that outbreaks of UWS and MPGAs are driven by elevated nutrient and organic carbon levels. Although the variables analyzed could be proxies for other causative agents (e.g., high sediment levels), the results provide quantitative evidence linking relatively higher coral disease prevalence to an anthropogenically impacted environment.

Laboratory-based surveillance of Neisseria meningitidis isolates from disease cases in Latin American and Caribbean countries, SIREVA II 2006-2010.

PubMed

Ibarz-Pavón, Ana Belén; Lemos, Ana Paula; Gorla, Maria Cecilia; Regueira, Mabel; Gabastou, Jean-Marc

2012-01-01

Published data on the epidemiology of meningococcal disease in Latin America and the Caribbean region is scarce and, when available, it is often published in Spanish and/or in non-peer-reviewed journals, making it difficult for the international scientific community to have access. Laboratory data on 4,735 Neisseria meningitidis strains was collected and reported by the National Reference Laboratories in 19 Latin American countries and the Caribbean Epidemiology Centre (CAREC) between 2006 and 2010 as part of the work carried out by the SIREVA II network. Serogroup and MIC to penicillin, rifampin and chloramphenicol were determined. Isolates were mainly obtained from patients <5 years, but each year around 25% of isolates came from adult patients. Serogroup distribution was highly variable among countries. Serogroup C was the main cause of disease in Brazil; the majority of disease seen in the Southern cone was caused by serogroup B, but serogroup W135 strains have increased in recent years. In the Andean and Mexico, Central America and Caribbean regions, serogroups B and C were equally present, and serogroup Y was frequently isolated. Isolates were generally susceptible to chloramphenicol, penicillin and rifampin, but almost 60% of isolates characterized in Southern cone countries presented intermediate resistance to penicillin. Five rifampin-resistant isolates have been isolated in Uruguay and Brazil. Serogroup distribution is highly variable among countries, but some geographic structuring can be inferred from these data. Epidemiological and laboratory data are scarce among Andean and Mexico, Central America and Caribbean countries. Evaluation and implementation of corrective measures on disease surveillance and reporting systems and the implementation of molecular diagnostic techniques and molecular characterization on meningococcal isolates are advised.

Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers.

PubMed

Lewis, James S; Scantlebury, Juliette B; Luo, Jingqin; Thorstad, Wade L

2012-07-01

Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any × 40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any × 40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (P<0.001), and both also correlated with histologic type (P<0.001 and P=0.01, respectively), p16 status (P=0.09 and 0.03, respectively), and partially with nodal extracapsular extension. There was no correlation with any of the other variables. In univariate analysis, cases showing anaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (P<0.006 for all). Higher T-stage, keratinizing histologic type, extracapsular extension, and smoking also all correlated with worse survival. In multivariate analysis, anaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P=0.04; and hazard ratio 11.9, P=0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival.

Tumor Cell Anaplasia and Multinucleation Are Predictors of Disease Recurrence in Oropharyngeal Squamous Cell Carcinoma, Including Among Just the Human Papillomavirus-Related Cancers

PubMed Central

Lewis, James S.; Scantlebury, Juliette B.; Luo, Jingqin; Thorstad, Wade L.

2013-01-01

Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any ×40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any ×40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (P < 0.001), and both also correlated with histologic type (P < 0.001 and P = 0.01, respectively), p16 status (P = 0.09 and 0.03, respectively), and partially with nodal extracapsular extension. There was no correlation with any of the other variables. In univariate analysis, cases showing anaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (P < 0.006 for all). Higher T-stage, keratinizing histologic type, extracapsular extension, and smoking also all correlated with worse survival. In multivariate analysis, anaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P = 0.04; and hazard ratio 11.9, P = 0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival. PMID:22743286

Iron deficiency across chronic kidney disease stages: Is there a reverse gender pattern?

PubMed

Aoun, Mabel; Karam, Rita; Sleilaty, Ghassan; Antoun, Leony; Ammar, Walid

2018-01-01

In non-dialysis chronic kidney disease patients, looking for iron deficiency is highly variable in practice and there is a great variability regarding the cutoffs used to treat iron deficiency. The aim of this study is to investigate the degree of iron deficiency in non-dialysis chronic kidney disease patients on erythropoiesis-stimulating agents. We included all non-dialysis chronic kidney disease patients that applied to the Lebanese Ministry of Public Health for erythropoiesis-stimulating agents' coverage during a 5-month period. Iron requirement was assessed based on two guidelines' target-to-treat cutoffs: 1-ferritin <100 ng/ml and/or TSAT < 20% (KDOQI 2006), 2- ferritin ≤500 ng/ml and TSAT ≤30% (KDIGO 2012). A total of 238 CKD patients were included over 5 months. All patients had a ferritin level in their record and 64% had an available TSAT. Median age was 71.0 (59.8-79.3) years and 61.8% were female. All had an eGFR<60 ml/min. The proportion of patients found to require iron therapy ranged between 48 and 78% with a trend towards higher values when using KDIGO-based criteria. Using ANCOVA test, inverse normal transformations of ferritin and TSAT showed a reverse pattern between men and women with women being more iron deficient in the early stage. Iron deficiency is highly prevalent in non-dialysis chronic kidney disease patients on erythropoiesis-stimulating agents' therapy. These findings reflect a lack in effective iron supplementation when managing anemia in pre-dialysis patients, especially in men at advanced stages. Renal societies should spread awareness about iron deficiency screening in those patients.

Quality of life of patients undergoing surgery by videolaparoscopy for GERD treatment.

PubMed

Andrade, Francisco José Cavalcante; de Almeida, Eliete Rodrigues; dos Santos, Maria Teresa Botti Rodrigues; Soares-Filho, Eurípedes; Lopes, João Batista; Veras e Silva, Roberto Cavalcante

2012-01-01

Gastroesophageal reflux disease is a chronic disease of high prevalence in Western countries, with negative effects on quality of life. Surgery is indicated for patients with intolerance to continuous medication, prolonged treatment or control, or in complicated forms of the disease. To evaluate the quality of life of patients undergoing surgery by videolaparoscopy for gastroesophageal reflux disease treatment. Sample comprised 43 patients of both genders (mean age = 51.4 years). For quality of life evaluation was made using the questionnaire Gastroesophageal Reflux Disease Health Related Quality of Life, translated and validated into Portuguese. Data were analyzed by Epi Info version 3.5.1, using Duncan test and Pearson's correlation coefficient, with 5% for null hypothesis (p ≤ 0.05). Over 50% of participants showed good quality of life (scores <5 of the questionnaire), more than 90% indicated satisfaction with their health. A significant positive correlation between most variables related to heartburn and the time after surgery was observed (p ≤ 0.05). Patients presented good quality of life and high level of satisfaction with their postoperative condition.

Time- and frequency-domain parameters of heart rate variability and sympathetic skin response in Parkinson's disease.

PubMed

Maetzler, Walter; Karam, Marie; Berger, Monika Fruhmann; Heger, Tanja; Maetzler, Corina; Ruediger, Heinz; Bronzova, Juliana; Lobo, Patricia Pita; Ferreira, Joaquim J; Ziemssen, Tjalf; Berg, Daniela

2015-03-01

The autonomic nervous system (ANS) is regularly affected in Parkinson's disease (PD). Information on autonomic dysfunction can be derived from e.g. altered heart rate variability (HRV) and sympathetic skin response (SSR). Such parameters can be quantified easily and measured repeatedly which might be helpful for evaluating disease progression and therapeutic outcome. In this 2-center study, HRV and SSR of 45 PD patients and 26 controls were recorded. HRV was measured during supine metronomic breathing and analyzed in time- and frequency-domains. SSR was evoked by repetitive auditory stimulation. Various ANS parameters were compared (1) between patients and healthy controls, (2) to clinical scales (Unified Parkinson's disease rating scale, Mini-Mental State Examination, Becks Depression Inventory), and (3) to disease duration. Root mean square of successive differences (RMSSD) and low frequency/high frequency (LF/HF) ratio differed significantly between PD and controls. Both, HRV and SSR parameters showed low or no association with clinical scores. Time-domain parameters tended to be affected already at early PD stages but did not consistently change with longer disease duration. In contrast, frequency-domain parameters were not altered in early PD phases but tended to be lower (LF, LF/HF ratio), respectively higher (HF) with increasing disease duration. This report confirms previous results of altered ANS parameters in PD. In addition, it suggests that (1) these ANS parameters are not relevantly associated with motor, behavioral, and cognitive changes in PD, (2) time-domain parameters are useful for the assessment of early PD, and (3) frequency-domain parameters are more closely associated with disease duration.

Health transition: examples from the western Pacific.

PubMed

Baker, P T; Garruto, R M

1992-12-01

The Industrial Revolution ushered in a rapid transition from agriculture to industrialization. Some biological effects of this transition included increasing life expectancy, reduced infant mortality, and some decline in fertility. Reduced infant mortality first brought about an increase in life expectancy, but as humans were able to control infectious diseases, child and adult mortality also decreased. Now, accidents and chronic diseases are responsible for most mortality in many age groups. This shift from infectious diseases to accidents and chronic diseases is called the health transition. Japan and US are Pacific Basin countries which have relatively high life expectancy and low infant mortality (1988, 75.54 years vs. 71.38 years, and 4.4 vs. 9.9, respectively). These figures suggest that these countries rather advanced in the health transition. Japan may have better life expectancy than the US because of the effect of environmental factors, ethnic diversity, and health care differentials by social class on cardiovascular disease and cancer mortality. China and Thailand hold intermediate positions (67.98 years (1985-1990) vs. 63.82 years (1985-1986), and 32.4 vs. 39, respectively). Some research indicates that urban conditions and factory work increase the cardiovascular disease risk among the Chinese. Recent research suggests that access to immunization and modern medical care for acute disease are the only critical variables of the health transition rather than other variables. Papua New Guinea is not progressing very well (53.18 years and 58). Papua New Guinea has not yet been able to control infectious diseases, especially malaria. This comparison illustrates that populations progress through the health transition at different rates.

[Risk and protection food consumption factors for chronic non-communicable diseases and their association with body fat: a study of employees in the health area of a public university in Recife in the state of Pernambuco, Brazil].

PubMed

Azevedo, Edynara Cristiane de Castro; Dias, Fábia Morgana Rodrigues da Silva; Diniz, Alcides da Silva; Cabral, Poliana Coelho

2014-05-01

This article seeks to assess the consumption of risk and protection foods for chronic non-communicable diseases and its association with body fat by health area workers in a public university in Recife in the state of Pernambuco. This cross-sectional study involved 267 adults. Two food groups were considered: risk and protection foods. Food consumption was assessed by a food frequency questionnaire with measurements converted to scores. The conceptual model considered socio-demographic, behavioral, and anthropometric variables. A high prevalence of overweight and low consumption of protection foods was detected. The average scores of risk and protection food consumption were similar in all variables analyzed, except for a higher consumption of protection foods observed in obese individuals (p = 0.000). The study highlights the complexity involved in the relation between food consumption, body fat, and chronic non-communicable diseases, indicating the need of future studies with more appropriate designs to provide input for future interventions in this population.

[Waardenburg syndrome. A heterogenic disorder with variable penetrance].

PubMed

Apaydin, F; Bereketoglu, M; Turan, O; Hribar, K; Maassen, M M; Günhan, O; Zenner, H-P; Pfister, M

2004-06-01

Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary anomalies of the skin, hairs, eyes and various defects of other neural crest derived tissues. It accounts for over 2% of congenital hearing impairment. At least four types are recognized on the basis of clinical and genetic criteria. Based on a screening of congenitally hearing impaired children, 12 families with WS type II were detected. Of special interest was the phenotype of these families, in particular the reduced penetrance of hearing impairment within the families. In all cases a high variability of the disease phenotype was detected and the penetrance of the clinical traits varied accordingly. Therefore, it is not possible to predict the clinical phenotype even in a single family. Based on these studies, we plan to identify the pathogenetic cause of the disease in order to perform a detailed genotype/phenotype analysis.

Mortality and Morbidity Risks and Economic Behavior

PubMed Central

Stoler, Avraham; Meltzer, David

2012-01-01

There are theoretical reasons to expect that high risk of mortality or morbidity during young adulthood decreases investment in human capital. However, investigation of this hypothesis is complicated by a variety of empirical challenges, including difficulties in inferring causation due to omitted variables and reverse causation. For example, to compare two groups with substantially different mortality rates, one typically has to use samples from different countries or time periods, making it difficult to control for other relevant variables. Reverse causation is important because human capital investment can affect mortality and morbidity. To counter these problems, we collected data on human capital investments, fertility decisions, and other economic choices of people at risk for Huntington’s disease. Huntington’s disease is a fatal genetic disorder that introduces a large and exogenous risk of early mortality and morbidity. We find a strong negative relation between mortality and morbidity risks and human capital investment. PMID:22308067

Dimension reduction techniques for the integrative analysis of multi-omics data

PubMed Central

Zeleznik, Oana A.; Thallinger, Gerhard G.; Kuster, Bernhard; Gholami, Amin M.

2016-01-01

State-of-the-art next-generation sequencing, transcriptomics, proteomics and other high-throughput ‘omics' technologies enable the efficient generation of large experimental data sets. These data may yield unprecedented knowledge about molecular pathways in cells and their role in disease. Dimension reduction approaches have been widely used in exploratory analysis of single omics data sets. This review will focus on dimension reduction approaches for simultaneous exploratory analyses of multiple data sets. These methods extract the linear relationships that best explain the correlated structure across data sets, the variability both within and between variables (or observations) and may highlight data issues such as batch effects or outliers. We explore dimension reduction techniques as one of the emerging approaches for data integration, and how these can be applied to increase our understanding of biological systems in normal physiological function and disease. PMID:26969681

Periodontal disease and its connection to systemic biomarkers of cardiovascular disease in young American Indian/Alaskan natives.

PubMed

Delange, Nicole; Lindsay, Suzanne; Lemus, Hector; Finlayson, Tracy L; Kelley, Scott T; Gottlieb, Roberta A

2018-02-01

Periodontal disease has been shown to be associated with cardiovascular disease (CVD). No known studies evaluate the relationship between periodontal disease status and biomarkers of CVD risk in the American Indian/Alaskan Native (AI/AN) population despite their disproportionately high rates of poor oral health and cardiovascular disease-related outcomes. This study compared levels of interleukin (IL)-6 and C-reactive protein (CRP) across increasing severity of periodontal disease status among younger adults between the ages of 21 and 43 years. Plasma levels of IL-6 and CRP were measured in adult participants (ages 21 to 43 years) as part of a study of periodontal disease and CVD risk among an AI/AN population in southern California (n = 59). Periodontal evaluations were performed and disease status was classified into three categories based on highest probing depth (none/mild: < 3 mm; moderate: 4 to 5 mm; severe: ≥6 mm). Participants with known systemic disease or active infection were excluded. Severe periodontitis was significantly associated with increased levels of IL-6 compared with those with none or mild periodontitis before controlling for other variables (P = 0.02), but lacked significance after controlling for sex, BMI, smoking status, and high-density lipoprotein (P = 0.09). Moderate periodontal disease was positively associated with IL-6 levels after controlling for potential confounders (P = 0.01). Periodontal status was not associated with CRP, before or after adjusting for covariates. In this otherwise healthy AI/AN adult sample, moderate periodontal disease compared with none or mild periodontal disease was associated with increased levels of IL-6. High levels of CRP found in this population warrant further research. © 2018 American Academy of Periodontology.

Monogenic autoimmune diseases of the endocrine system.

PubMed

Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

2016-10-01

The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel Strategy to Evaluate Infectious Salmon Anemia Virus Variants by High Resolution Melting

PubMed Central

Sepúlveda, Dagoberto; Cárdenas, Constanza; Carmona, Marisela; Marshall, Sergio H.

2012-01-01

Genetic variability is a key problem in the prevention and therapy of RNA-based virus infections. Infectious Salmon Anemia virus (ISAv) is an RNA virus which aggressively attacks salmon producing farms worldwide and in particular in Chile. Just as with most of the Orthomyxovirus, ISAv displays high variability in its genome which is reflected by a wider infection potential, thus hampering management and prevention of the disease. Although a number of widely validated detection procedures exist, in this case there is a need of a more complex approach to the characterization of virus variability. We have adapted a procedure of High Resolution Melting (HRM) as a fine-tuning technique to fully differentiate viral variants detected in Chile and projected to other infective variants reported elsewhere. Out of the eight viral coding segments, the technique was adapted using natural Chilean variants for two of them, namely segments 5 and 6, recognized as virulence-associated factors. Our work demonstrates the versatility of the technique as well as its superior resolution capacity compared with standard techniques currently in use as key diagnostic tools. PMID:22719837

Climatic, high tide and vector variables and the transmission of Ross River virus.

PubMed

Tong, S; Hu, W; Nicholls, N; Dale, P; MacKenzie, J S; Patz, J; McMichael, A J

2005-11-01

This report assesses the impact of the variability in environmental and vector factors on the transmission of Ross River virus (RRV) in Brisbane, Australia. Poisson time series regression analyses were conducted using monthly data on the counts of RRV cases, climate variables (Southern Oscillation Index and rainfall), high tides and mosquito density for the period of 1998-2001. The results indicate that increases in the high tide (relative risk (RR): 1.65; 95% confidence interval (CI): 1.20-2.26), rainfall (RR: 1.45; 95% CI: 1.21-1.73), mosquito density (RR: 1.17; 95% CI: 1.09-1.27), the density of Culex annulirostris (RR: 1.25; 95% CI: 1.13-1.37) and the density of Ochlerotatus vigilax (RR: 2.39; 95% CI: 2.30-2.48), each at a lag of 1 month, were statistically significantly associated with the rise of monthly RRV incidence. The results of the present study might facilitate the development of early warning systems for reducing the incidence of this wide-spread disease in Australia and other Pacific island nations.

High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease.

PubMed

Bristow, Robert E; Chang, Jenny; Ziogas, Argyrios; Randall, Leslie M; Anton-Culver, Hoda

2014-02-01

To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers. Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥20 cases/year), high-volume physicians (HVP) (≥10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables. A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16-1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22-2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07-2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46-4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90-4.23). Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities. Copyright © 2013 Elsevier Inc. All rights reserved.

Relation between lung function, exercise capacity, and exposure to asbestos cement.

PubMed Central

Wollmer, P; Eriksson, L; Jonson, B; Jakobsson, K; Albin, M; Skerfving, S; Welinder, H

1987-01-01

A group of 137 male workers with known exposure (mean 20 fibre years per millilitre) to asbestos cement who had symptoms or signs of pulmonary disease was studied together with a reference group of 49 healthy industrial workers with no exposure to asbestos. Lung function measurements were made at rest and during exercise. Evidence of lung fibrosis was found as well as of obstructive airways disease in the exposed group compared with the reference group. Asbestos cement exposure was related to variables reflecting lung fibrosis but not to variables reflecting airflow obstruction. Smoking was related to variables reflecting obstructive lung disease. Exercise capacity was reduced in the exposed workers and was related to smoking and to lung function variables, reflecting obstructive airways disease. There was no significant correlation between exercise capacity and exposure to asbestos cement. PMID:3651353

Coherent Somatic Mutation in Autoimmune Disease

PubMed Central

Ross, Kenneth Andrew

2014-01-01

Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases. PMID:24988487

The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention

PubMed Central

DePalma, Ralph G.; Shamayeva, Galina; Chow, Bruce K.

2013-01-01

Objectives. We postulated the existence of a statin–iron nexus by which statins improve cardiovascular disease outcomes at least partially by countering proinflammatory effects of excess iron stores. Methods. Using data from a clinical trial of iron (ferritin) reduction in advanced peripheral arterial disease, the Iron and Atherosclerosis Study, we compared effects of ferritin levels versus high-density lipoprotein to low-density lipoprotein ratios (both were randomization variables) on clinical outcomes in participants receiving and not receiving statins. Results. Statins increased high-density lipoprotein to low-density lipoprotein ratios and reduced ferritin levels by noninteracting mechanisms. Improved clinical outcomes were associated with lower ferritin levels but not with improved lipid status. Conclusions. There are commonalities between the clinical benefits of statins and the maintenance of physiologic iron levels. Iron reduction may be a safe and low-cost alternative to statins. PMID:23409890

International travellers from New Jersey: piloting a travel health module in the 2011 Behavioral Risk Factor Surveillance System survey.

PubMed

Stoney, Rhett J; Kozarsky, Phyllis; Bostick, Roberd M; Sotir, Mark J

2016-01-01

In 2011, the Centers for Disease Control and Prevention and the New Jersey Department of Health used the New Jersey Behavioral Risk Factor Survey (NJBRFS), a state component of the national Behavioral Risk Factor Surveillance System (BRFSS) to pilot a travel health module designed to collect population-based data on New Jersey residents travelling internationally. Our objective was to use this population-based travel health information to serve as a baseline to evaluate trends in US international travellers. A representative sample of New Jersey residents was identified through a random-digit-dialing method and administered the travel health module, which asked five questions: travel outside of USA during the previous year; destination; purpose; if a healthcare provider was visited before travel and any travel-related illness. Additional health variables from the larger NJBRFS were considered and included in bivariate analyses and multiple logistic regression; weights were assigned to variables to account for survey design complexity. Of 4029 participants, 841 (21%) travelled internationally. Top destinations included Mexico (10%), Canada (9%), Dominican Republic (6%), Bahamas (5%) and Italy (5%). Variables positively associated with travel included foreign birth, ≥$75 000 annual household income, college education and no children living in the household. One hundred fifty (18%) of 821 travellers with known destinations went to high-risk countries; 40% were visiting friends and relatives and only 30% sought pre-travel healthcare. Forty-eight (6%) of 837 responding travellers reported travel-related illness; 44% visited high-risk countries. Approximately one in five NJBRFS respondents travelled internationally during the previous year, a sizeable proportion to high-risk destinations. Few reported becoming ill as a result of travel but almost one-half of those ill had travelled to high-risk destinations. Population-based surveillance data on travellers can help document trends in destinations, traveller type and disease prevalence and evaluate the effectiveness of disease prevention programmmes. Published by Oxford University Press International Society of Travel Medicine 2016. This work is written by US Government employees and is in the public domain in the US.

A comparison of urinary tract pathology and morbidity in adult populations from endemic and non-endemic zones for urinary schistosomiasis on Unguja Island, Zanzibar

PubMed Central

2009-01-01

Background Renal tract involvement is implicated in both early and late schistosomiasis leading to increased disease burden. Despite there being good estimates of disease burden due to renal tract disease secondary to schistosomiasis at the global level, it is often difficult to translate these estimates into local communities. The aim of this study was to assess the burden of urinary tract pathology and morbidity due to schistosomiasis in Zanzibar and identify reliable clinical predictors of schistosomiasis associated renal disease. Methods A cross-sectional comparison of Ungujan men and women living within either high or low endemic areas for urinary schistosomiasis was conducted. Using urine analysis with reagent strips, parasitological egg counts, portable ultrasonography and a qualitative case-history questionnaire. Data analysis used single and multiple predictor variable logistic regression. Results One hundred and sixty people were examined in the high endemic area (63% women and 37% men), and 101 people in the low endemic area (61% women and 39% men). In the high endemic area, egg-patent schistosomiasis and urinary tract pathology were much more common (p = 1 × 10-3, 8 × 10-6, respectively) in comparison with the low endemic area. Self-reported frothy urine, self-reported haematuria, dysuria and urgency to urinate were associated with urinary tract pathology (p = 1.8 × 10-2, p = 1.1 × 10-4, p = 1.3 × 10-6, p = 1.1 × 10-7, respectively) as assessed by ultrasonography. In a multi-variable logistic regression model, self-reporting of schistosomiasis in the past year, self-reporting of urgency to urinate and having an egg-positive urine sample were all independently associated with detectable urinary tract abnormality, consistent with schistosomiasis-specific disease. Having two or more of these features was moderately sensitive (70%) as a predictor for urinary tract abnormality with high specificity (92%). Conclusion Having two out of urgency to urinate, self reporting of previous infections and detection of eggs in the urine were good proxy predictors of urinary tract abnormality as detected by ultrasound. PMID:19943968

A comparison of urinary tract pathology and morbidity in adult populations from endemic and non-endemic zones for urinary schistosomiasis on Unguja Island, Zanzibar.

PubMed

Lyons, Beatrice; Stothard, Russel; Rollinson, David; Khamis, Simba; Simai, Khamis A; Hunter, Paul R

2009-11-29

Renal tract involvement is implicated in both early and late schistosomiasis leading to increased disease burden. Despite there being good estimates of disease burden due to renal tract disease secondary to schistosomiasis at the global level, it is often difficult to translate these estimates into local communities. The aim of this study was to assess the burden of urinary tract pathology and morbidity due to schistosomiasis in Zanzibar and identify reliable clinical predictors of schistosomiasis associated renal disease. A cross-sectional comparison of Ungujan men and women living within either high or low endemic areas for urinary schistosomiasis was conducted. Using urine analysis with reagent strips, parasitological egg counts, portable ultrasonography and a qualitative case-history questionnaire. Data analysis used single and multiple predictor variable logistic regression. One hundred and sixty people were examined in the high endemic area (63% women and 37% men), and 101 people in the low endemic area (61% women and 39% men). In the high endemic area, egg-patent schistosomiasis and urinary tract pathology were much more common (p = 1 x 10-3, 8 x 10-6, respectively) in comparison with the low endemic area. Self-reported frothy urine, self-reported haematuria, dysuria and urgency to urinate were associated with urinary tract pathology (p = 1.8 x 10-2, p = 1.1 x 10-4, p = 1.3 x 10-6, p = 1.1 x 10-7, respectively) as assessed by ultrasonography. In a multi-variable logistic regression model, self-reporting of schistosomiasis in the past year, self-reporting of urgency to urinate and having an egg-positive urine sample were all independently associated with detectable urinary tract abnormality, consistent with schistosomiasis-specific disease. Having two or more of these features was moderately sensitive (70%) as a predictor for urinary tract abnormality with high specificity (92%). Having two out of urgency to urinate, self reporting of previous infections and detection of eggs in the urine were good proxy predictors of urinary tract abnormality as detected by ultrasound.

Melorheostosis: a rare entity: a case report.

PubMed

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease.

Melorheostosis: a rare entity: a case report

PubMed Central

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease. PMID:25489356

Application of a new approach for characterization and denomination of races of cucurbit powdery mildews – a case study on the Czech pathogen population

USDA-ARS?s Scientific Manuscript database

Golovinomyces cichoracearum (Gc) and Podosphaera xanthii (Px) (Ascomycetes, Erysiphaceae) are the most important fungal species causing cucurbit powdery mildew (CPM), a serious disease of field and greenhouse cucurbits. Both species are highly variable, as indicated by the existence of large number ...

Validity of Suicidality Items from the Youth Risk Behavior Survey in a High School Sample

ERIC Educational Resources Information Center

May, Alexis; Klonsky, E. David

2011-01-01

The Youth Risk Behavior Survey (YRBS) is used by the United States Centers for Disease Control to estimate rates of suicidal thoughts and behaviors in adolescents. This study investigated the validity of the YRBS suicidality items by examining their relationship to criterion variables including loneliness, anxiety, depression, substance use, and…

Quantitative contrast enhanced magnetic resonance imaging for the evaluation of peripheral arterial disease: a comparative study versus standard digital angiography.

PubMed

Pavlovic, Chris; Futamatsu, Hideki; Angiolillo, Dominick J; Guzman, Luis A; Wilke, Norbert; Siragusa, Daniel; Wludyka, Peter; Percy, Robert; Northrup, Martin; Bass, Theodore A; Costa, Marco A

2007-04-01

The purpose of this study is to evaluate the accuracy of semiautomated analysis of contrast enhanced magnetic resonance angiography (MRA) in patients who have undergone standard angiographic evaluation for peripheral vascular disease (PVD). Magnetic resonance angiography is an important tool for evaluating PVD. Although this technique is both safe and noninvasive, the accuracy and reproducibility of quantitative measurements of disease severity using MRA in the clinical setting have not been fully investigated. 43 lesions in 13 patients who underwent both MRA and digital subtraction angiography (DSA) of iliac and common femoral arteries within 6 months were analyzed using quantitative magnetic resonance angiography (QMRA) and quantitative vascular analysis (QVA). Analysis was repeated by a second operator and by the same operator in approximately 1 month time. QMRA underestimated percent diameter stenosis (%DS) compared to measurements made with QVA by 2.47%. Limits of agreement between the two methods were +/- 9.14%. Interobserver variability in measurements of %DS were +/- 12.58% for QMRA and +/- 10.04% for QVA. Intraobserver variability of %DS for QMRA was +/- 4.6% and for QVA was +/- 8.46%. QMRA displays a high level of agreement to QVA when used to determine stenosis severity in iliac and common femoral arteries. Similar levels of interobserver and intraobserver variability are present with each method. Overall, QMRA represents a useful method to quantify severity of PVD.

Development of a novel diagnostic algorithm to predict NASH in HCV-positive patients.

PubMed

Gallotta, Andrea; Paneghetti, Laura; Mrázová, Viera; Bednárová, Adriana; Kružlicová, Dáša; Frecer, Vladimir; Miertus, Stanislav; Biasiolo, Alessandra; Martini, Andrea; Pontisso, Patrizia; Fassina, Giorgio

2018-05-01

Non-alcoholic steato-hepatitis (NASH) is a severe disease characterised by liver inflammation and progressive hepatic fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that in hepatitis C virus patients steatosis and NASH are associated with faster fibrosis progression and hepatocellular carcinoma. A safe and reliable non-invasive diagnostic method to detect NASH at its early stages is still needed to prevent progression of the disease. We prospectively enrolled 91 hepatitis C virus-positive patients with histologically proven chronic liver disease: 77 patients were included in our study; of these, 10 had NASH. For each patient, various clinical and serological variables were collected. Different algorithms combining squamous cell carcinoma antigen-immunoglobulin-M (SCCA-IgM) levels with other common clinical data were created to provide the probability of having NASH. Our analysis revealed a statistically significant correlation between the histological presence of NASH and SCCA-IgM, insulin, homeostasis model assessment, haemoglobin, high-density lipoprotein and ferritin levels, and smoke. Compared to the use of a single marker, algorithms that combined four, six or seven variables identified NASH with higher accuracy. The best diagnostic performance was obtained with the logistic regression combination, which included all seven variables correlated with NASH. The combination of SCCA-IgM with common clinical data shows promising diagnostic performance for the detection of NASH in hepatitis C virus patients.

Parameter estimation and prediction for the course of a single epidemic outbreak of a plant disease.

PubMed

Kleczkowski, A; Gilligan, C A

2007-10-22

Many epidemics of plant diseases are characterized by large variability among individual outbreaks. However, individual epidemics often follow a well-defined trajectory which is much more predictable in the short term than the ensemble (collection) of potential epidemics. In this paper, we introduce a modelling framework that allows us to deal with individual replicated outbreaks, based upon a Bayesian hierarchical analysis. Information about 'similar' replicate epidemics can be incorporated into a hierarchical model, allowing both ensemble and individual parameters to be estimated. The model is used to analyse the data from a replicated experiment involving spread of Rhizoctonia solani on radish in the presence or absence of a biocontrol agent, Trichoderma viride. The rate of primary (soil-to-plant) infection is found to be the most variable factor determining the final size of epidemics. Breakdown of biological control in some replicates results in high levels of primary infection and increased variability. The model can be used to predict new outbreaks of disease based upon knowledge from a 'library' of previous epidemics and partial information about the current outbreak. We show that forecasting improves significantly with knowledge about the history of a particular epidemic, whereas the precision of hindcasting to identify the past course of the epidemic is largely independent of detailed knowledge of the epidemic trajectory. The results have important consequences for parameter estimation, inference and prediction for emerging epidemic outbreaks.

Cryptic chytridiomycosis linked to climate and genetic variation in amphibian populations of the southeastern United States

PubMed Central

Hoffman, Eric A.; Tye, Matthew R.; Hether, Tyler D.; Savage, Anna E.

2017-01-01

North American amphibians have recently been impacted by two major emerging pathogens, the fungus Batrachochytrium dendrobatidis (Bd) and iridoviruses in the genus Ranavirus (Rv). Environmental factors and host genetics may play important roles in disease dynamics, but few studies incorporate both of these components into their analyses. Here, we investigated the role of environmental and genetic factors in driving Bd and Rv infection prevalence and severity in a biodiversity hot spot, the southeastern United States. We used quantitative PCR to characterize Bd and Rv dynamics in natural populations of three amphibian species: Notophthalmus perstriatus, Hyla squirella and Pseudacris ornata. We combined pathogen data, genetic diversity metrics generated from neutral markers, and environmental variables into general linear models to evaluate how these factors impact infectious disease dynamics. Occurrence, prevalence and intensity of Bd and Rv varied across species and populations, but only one species, Pseudacris ornata, harbored high Bd intensities in the majority of sampled populations. Genetic diversity and climate variables both predicted Bd prevalence, whereas climatic variables alone predicted infection intensity. We conclude that Bd is more abundant in the southeastern United States than previously thought and that genetic and environmental factors are both important for predicting amphibian pathogen dynamics. Incorporating both genetic and environmental information into conservation plans for amphibians is necessary for the development of more effective management strategies to mitigate the impact of emerging infectious diseases. PMID:28448517

Heart rate variability is differentially altered in multiple sclerosis: implications for acute, worsening and progressive disability.

PubMed

Studer, Valeria; Rocchi, Camilla; Motta, Caterina; Lauretti, Benedetta; Perugini, Jacopo; Brambilla, Laura; Pareja-Gutierrez, Lorena; Camera, Giorgia; Barbieri, Francesca Romana; Marfia, Girolama A; Centonze, Diego; Rossi, Silvia

2017-01-01

Sympathovagal imbalance has been associated with poor prognosis in chronic diseases, but there is conflicting evidence in multiple sclerosis. The objective of this study was to investigate the autonomic nervous system dysfunction correlation with inflammation and progression in multiple sclerosis. Heart rate variability was analysed in 120 multiple sclerosis patients and 60 healthy controls during supine rest and head-up tilt test; the normalised units of low frequency and high frequency power were considered to assess sympathetic and vagal components, respectively. Correlation analyses with clinical and radiological markers of disease activity and progression were performed. Sympathetic dysfunction was closely related to the progression of disability in multiple sclerosis: progressive patients showed altered heart rate variability with respect to healthy controls and relapsing-remitting patients, with higher rest low frequency power and lacking the expected low frequency power increase during the head-up tilt test. In relapsing-remitting patients, disease activity, even subclinical, was associated with lower rest low frequency power, whereas stable relapsing-remitting patients did not differ from healthy controls. Less sympathetic reactivity and higher low frequency power at rest were associated with incomplete recovery from relapse. Autonomic balance appears to be intimately linked with both the inflammatory activity of multiple sclerosis, which is featured by an overall hypoactivity of the sympathetic nervous system, and its compensatory plastic processes, which appear inefficient in case of worsening and progressive multiple sclerosis.

The Quality of Rare Disease Registries: Evaluation and Characterization.

PubMed

Coi, Alessio; Santoro, Michele; Villaverde-Hueso, Ana; Lipucci Di Paola, Michele; Gainotti, Sabina; Taruscio, Domenica; Posada de la Paz, Manuel; Bianchi, Fabrizio

2016-01-01

The focus on the quality of the procedures for data collection, storing, and analysis in the definition and implementation of a rare disease registry (RDR) is the basis for developing a valid and long-term sustainable tool. The aim of this study was to provide useful information for characterizing a quality profile for RDRs using an analytical approach applied to RDRs participating in the European Platform for Rare Disease Registries 2011-2014 (EPIRARE) survey. An indicator of quality was defined by choosing a small set of quality-related variables derived from the survey. The random forest method was used to identify the variables best defining a quality profile for RDRs. Fisher's exact test was employed to assess the association with the indicator of quality, and the Cochran-Armitage test was used to check the presence of a linear trend along different levels of quality. The set of variables found to characterize high-quality RDRs focused on ethical and legal issues, governance, communication of activities and results, established procedures to regulate access to data and security, and established plans to ensure long-term sustainability. The quality of RDRs is usually associated with a good oversight and governance mechanism and with durable funding. The results suggest that RDRs would benefit from support in management, information technology, epidemiology, and statistics. © 2016 S. Karger AG, Basel.

Disease and thermal acclimation in a more variable and unpredictable climate

NASA Astrophysics Data System (ADS)

Raffel, Thomas R.; Romansic, John M.; Halstead, Neal T.; McMahon, Taegan A.; Venesky, Matthew D.; Rohr, Jason R.

2013-02-01

Global climate change is shifting the distribution of infectious diseases of humans and wildlife with potential adverse consequences for disease control. As well as increasing mean temperatures, climate change is expected to increase climate variability, making climate less predictable. However, few empirical or theoretical studies have considered the effects of climate variability or predictability on disease, despite it being likely that hosts and parasites will have differential responses to climatic shifts. Here we present a theoretical framework for how temperature variation and its predictability influence disease risk by affecting host and parasite acclimation responses. Laboratory experiments conducted in 80 independent incubators, and field data on disease-associated frog declines in Latin America, support the framework and provide evidence that unpredictable temperature fluctuations, on both monthly and diurnal timescales, decrease frog resistance to the pathogenic chytrid fungus Batrachochytrium dendrobatidis. Furthermore, the pattern of temperature-dependent growth of the fungus on frogs was opposite to the pattern of growth in culture, emphasizing the importance of accounting for the host-parasite interaction when predicting climate-dependent disease dynamics. If similar acclimation responses influence other host-parasite systems, as seems likely, then present models, which generally ignore small-scale temporal variability in climate, might provide poor predictions for climate effects on disease.

Differential modulation of eastern oyster ( Crassostrea virginica) disease parasites by the El-Niño-Southern Oscillation and the North Atlantic Oscillation

NASA Astrophysics Data System (ADS)

Soniat, Thomas M.; Hofmann, Eileen E.; Klinck, John M.; Powell, Eric N.

2009-02-01

The eastern oyster ( Crassostrea virginica) is affected by two protozoan parasites, Perkinsus marinus which causes Dermo disease and Haplosporidium nelsoni which causes MSX (Multinucleated Sphere Unknown) disease. Both diseases are largely controlled by water temperature and salinity and thus are potentially sensitive to climate variations resulting from the El Niño-Southern Oscillation (ENSO), which influences climate along the Gulf of Mexico coast, and the North Atlantic Oscillation (NAO), which influences climate along the Atlantic coast of the United States. In this study, a 10-year time series of temperature and salinity and P. marinus infection intensity for a site in Louisiana on the Gulf of Mexico coast and a 52-year time series of air temperature and freshwater inflow and oyster mortality from Delaware Bay on the Atlantic coast of the United States were analyzed to determine patterns in disease and disease-induced mortality in C. virginica populations that resulted from ENSO and NAO climate variations. Wavelet analysis was used to decompose the environmental, disease infection intensity and oyster mortality time series into a time-frequency space to determine the dominant modes of variability and the time variability of the modes. For the Louisiana site, salinity and Dermo disease infection intensity are correlated at a periodicity of 4 years, which corresponds to ENSO. The influence of ENSO on Dermo disease along the Gulf of Mexico is through its effect on salinity, with high salinity, which occurs during the La Niña phase of ENSO at this location, favoring parasite proliferation. For the Delaware Bay site, the primary correlation was between temperature and oyster mortality, with a periodicity of 8 years, which corresponds to the NAO. Warmer temperatures, which occur during the positive phase of the NAO, favor the parasites causing increased oyster mortality. Thus, disease prevalence and intensity in C. virginica populations along the Gulf of Mexico coast is primarily regulated by salinity, whereas temperature regulates the disease process along the United States east coast. These results show that the response of an organism to climate variability in a region is not indicative of the response that will occur over the entire range of a particular species. This has important implications for management of marine resources, especially those that are commercially harvested.

Dengue: recent past and future threats

PubMed Central

Rogers, David J.

2015-01-01

This article explores four key questions about statistical models developed to describe the recent past and future of vector-borne diseases, with special emphasis on dengue: (1) How many variables should be used to make predictions about the future of vector-borne diseases?(2) Is the spatial resolution of a climate dataset an important determinant of model accuracy?(3) Does inclusion of the future distributions of vectors affect predictions of the futures of the diseases they transmit?(4) Which are the key predictor variables involved in determining the distributions of vector-borne diseases in the present and future?Examples are given of dengue models using one, five or 10 meteorological variables and at spatial resolutions of from one-sixth to two degrees. Model accuracy is improved with a greater number of descriptor variables, but is surprisingly unaffected by the spatial resolution of the data. Dengue models with a reduced set of climate variables derived from the HadCM3 global circulation model predictions for the 1980s are improved when risk maps for dengue's two main vectors (Aedes aegypti and Aedes albopictus) are also included as predictor variables; disease and vector models are projected into the future using the global circulation model predictions for the 2020s, 2040s and 2080s. The Garthwaite–Koch corr-max transformation is presented as a novel way of showing the relative contribution of each of the input predictor variables to the map predictions. PMID:25688021

Assessing the risk of bovine fasciolosis using linear regression analysis for the state of Rio Grande do Sul, Brazil.

PubMed

Silva, Ana Elisa Pereira; Freitas, Corina da Costa; Dutra, Luciano Vieira; Molento, Marcelo Beltrão

2016-02-15

Fasciola hepatica is the causative agent of fasciolosis, a disease that triggers a chronic inflammatory process in the liver affecting mainly ruminants and other animals including humans. In Brazil, F. hepatica occurs in larger numbers in the most Southern state of Rio Grande do Sul. The objective of this study was to estimate areas at risk using an eight-year (2002-2010) time series of climatic and environmental variables that best relate to the disease using a linear regression method to municipalities in the state of Rio Grande do Sul. The positivity index of the disease, which is the rate of infected animal per slaughtered animal, was divided into three risk classes: low, medium and high. The accuracy of the known sample classification on the confusion matrix for the low, medium and high rates produced by the estimated model presented values between 39 and 88% depending of the year. The regression analysis showed the importance of the time-based data for the construction of the model, considering the two variables of the previous year of the event (positivity index and maximum temperature). The generated data is important for epidemiological and parasite control studies mainly because F. hepatica is an infection that can last from months to years. Copyright © 2015 Elsevier B.V. All rights reserved.

Test-Retest Reliability of Diffusion Tensor Imaging in Huntington's Disease.

PubMed

Cole, James H; Farmer, Ruth E; Rees, Elin M; Johnson, Hans J; Frost, Chris; Scahill, Rachael I; Hobbs, Nicola Z

2014-03-21

Diffusion tensor imaging (DTI) has shown microstructural abnormalities in patients with Huntington's Disease (HD) and work is underway to characterise how these abnormalities change with disease progression. Using methods that will be applied in longitudinal research, we sought to establish the reliability of DTI in early HD patients and controls. Test-retest reliability, quantified using the intraclass correlation coefficient (ICC), was assessed using region-of-interest (ROI)-based white matter atlas and voxelwise approaches on repeat scan data from 22 participants (10 early HD, 12 controls). T1 data was used to generate further ROIs for analysis in a reduced sample of 18 participants. The results suggest that fractional anisotropy (FA) and other diffusivity metrics are generally highly reliable, with ICCs indicating considerably lower within-subject compared to between-subject variability in both HD patients and controls. Where ICC was low, particularly for the diffusivity measures in the caudate and putamen, this was partly influenced by outliers. The analysis suggests that the specific DTI methods used here are appropriate for cross-sectional research in HD, and give confidence that they can also be applied longitudinally, although this requires further investigation. An important caveat for DTI studies is that test-retest reliability may not be evenly distributed throughout the brain whereby highly anisotropic white matter regions tended to show lower relative within-subject variability than other white or grey matter regions.

Virological and serological findings in dogs with naturally occurring distemper.

PubMed

Elia, Gabriella; Camero, Michele; Losurdo, Michele; Lucente, Maria Stella; Larocca, Vittorio; Martella, Vito; Decaro, Nicola; Buonavoglia, Canio

2015-03-01

Canine distemper virus (CDV) is the cause of a severe and highly contagious disease in dogs. The unpredictable and variable course of CDV-related disease may hamper correct diagnosis of infection and makes it crucial the collection of samples suitable for laboratory confirmation. In the present study we were able to follow the disease in two dogs infected naturally, collecting different biological matrices during the entire period of infection. By real time RT-PCR, viral RNA was detected and quantified, suggesting that urine and rectal swabs would be useful for ante-mortem diagnosis of distemper in dogs, regardless of the clinical stage and form of the illness. Copyright © 2015 Elsevier B.V. All rights reserved.

Correlates of protection against human rotavirus disease and the factors influencing protection in low-income settings.

PubMed

Clarke, E; Desselberger, U

2015-01-01

Rotaviruses (RV) are the leading cause of gastroenteritis in infants and children worldwide and are associated with high mortality predominately in low-income settings. The virus is classified into G and P serotypes and further into P genotypes based on differences in the surface-exposed proteins VP7 and VP4, respectively. Infection results in a variable level of protection from subsequent reinfection and disease. This protection is predominantly homotypic in some settings, whereas broader heterotypic protection is reported in other cohorts. Two antigenically distinct oral RV vaccines are licensed and are being rolled out widely, including in resource-poor setting, with funding provided by the GAVI alliance. First is a monovalent vaccine derived from a live-attenuated human RV strain, whereas the second is a pentavalent bovine-human reassortment vaccine. Both vaccines are highly efficacious in high-income settings, but greatly reduced levels of protection are reported in low-income countries. Here, the current challenges facing mucosal immunologists and vaccinologists aiming to define immunological correlates and to understand the variable levels of protection conferred by these vaccines in humans is considered. Such understanding is critical to maximize the public health impact of the current vaccines and also to the development of the next generation of RV vaccines, which are needed.

Application of portfolio theory to risk-based allocation of surveillance resources in animal populations.

PubMed

Prattley, D J; Morris, R S; Stevenson, M A; Thornton, R

2007-09-14

Distribution of finite levels of resources between multiple competing tasks can be a challenging problem. Resources need to be distributed across time periods and geographic locations to increase the probability of detection of a disease incursion or significant change in disease pattern. Efforts should focus primarily on areas and populations where risk factors for a given disease reach relatively high levels. In order to target resources into these areas, the overall risk level can be evaluated periodically across locations to create a dynamic national risk landscape. Methods are described to integrate the levels of various risk factors into an overall risk score for each area, to account for the certainty or variability around those measures and then to allocate surveillance resources across this risk landscape. In addition to targeting resources into high risk areas, surveillance continues in lower risk areas where there is a small yet positive chance of disease occurrence. In this paper we describe the application of portfolio theory concepts, routinely used in finance, to design surveillance portfolios for a series of examples. The appropriate level of resource investment is chosen for each disease or geographical area and time period given the degree of disease risk and uncertainty present.

Deciphering protein signatures using color, morphological, and topological analysis of immunohistochemically stained human tissues

NASA Astrophysics Data System (ADS)

Zerhouni, Erwan; Prisacari, Bogdan; Zhong, Qing; Wild, Peter; Gabrani, Maria

2016-03-01

Images of tissue specimens enable evidence-based study of disease susceptibility and stratification. Moreover, staining technologies empower the evidencing of molecular expression patterns by multicolor visualization, thus enabling personalized disease treatment and prevention. However, translating molecular expression imaging into direct health benefits has been slow. Two major factors contribute to that. On the one hand, disease susceptibility and progression is a complex, multifactorial molecular process. Diseases, such as cancer, exhibit cellular heterogeneity, impeding the differentiation between diverse grades or types of cell formations. On the other hand, the relative quantification of the stained tissue selected features is ambiguous, tedious and time consuming, prone to clerical error, leading to intra- and inter-observer variability and low throughput. Image analysis of digital histopathology images is a fast-developing and exciting area of disease research that aims to address the above limitations. We have developed a computational framework that extracts unique signatures using color, morphological and topological information and allows the combination thereof. The integration of the above information enables diagnosis of disease with AUC as high as 0.97. Multiple staining show significant improvement with respect to most proteins, and an AUC as high as 0.99.

Perioperative Near-Infrared Spectroscopy Monitoring in Neonates With Congenital Heart Disease: Relationship of Cerebral Tissue Oxygenation Index Variability With Neurodevelopmental Outcome.

PubMed

Spaeder, Michael C; Klugman, Darren; Skurow-Todd, Kami; Glass, Penny; Jonas, Richard A; Donofrio, Mary T

2017-03-01

To evaluate the value of perioperative cerebral near-infrared spectroscopy monitoring using variability analysis in the prediction of neurodevelopmental outcomes in neonates undergoing surgery for congenital heart disease. Retrospective cohort study. Urban, academic, tertiary-care children's hospital. Neonates undergoing surgery with cardiopulmonary bypass for congenital heart disease. Perioperative monitoring of continuous cerebral tissue oxygenation index by near-infrared spectroscopy and subsequent neurodevelopmental testing at 6, 15, and 21 months of age. We developed a new measure, cerebral tissue oxygenation index variability, using the root mean of successive squared differences of averaged 1-minute cerebral tissue oxygenation index values for both the intraoperative and first 24-hours postoperative phases of monitoring. There were 62 neonates who underwent cerebral tissue oxygenation index monitoring during surgery for congenital heart disease and 44 underwent subsequent neurodevelopmental testing (12 did not survive until testing and six were lost to follow-up). Among the 44 monitored patients who underwent neurodevelopmental testing, 20 (45%) had abnormal neurodevelopmental indices. Patients with abnormal neurodevelopmental indices had lower postoperative cerebral tissue oxygenation index variability when compared with patients with normal indices (p = 0.01). Adjusting for class of congenital heart disease and duration of deep hypothermic circulatory arrest, lower postoperative cerebral tissue oxygenation index variability was associated with poor neurodevelopmental outcome (p = 0.02). We found reduced postoperative cerebral tissue oxygenation index variability in neonatal survivors of congenital heart disease surgery with poor neurodevelopmental outcomes. We hypothesize that reduced cerebral tissue oxygenation index variability may be a surrogate for impaired cerebral metabolic autoregulation in the immediate postoperative period. Further research is needed to investigate clinical implications of this finding and opportunities for using this measure to drive therapeutic interventions.

Assessment of Human Health Vulnerability to Climate Variability and Change in Cuba

PubMed Central

Bultó, Paulo Lázaro Ortíz; Rodríguez, Antonio Pérez; Valencia, Alina Rivero; Vega, Nicolás León; Gonzalez, Manuel Díaz; Carrera, Alina Pérez

2006-01-01

In this study we assessed the potential effects of climate variability and change on population health in Cuba. We describe the climate of Cuba as well as the patterns of climate-sensitive diseases of primary concern, particularly dengue fever. Analyses of the associations between climatic anomalies and disease patterns highlight current vulnerability to climate variability. We describe current adaptations, including the application of climate predictions to prevent disease outbreaks. Finally, we present the potential economic costs associated with future impacts due to climate change. The tools used in this study can be useful in the development of appropriate and effective adaptation options to address the increased climate variability associated with climate change. PMID:17185289

Rare diseases, rare presentations: recognizing atypical inherited kidney disease phenotypes in the age of genomics.

PubMed

Ars, Elisabet; Torra, Roser

2017-10-01

A significant percentage of adults (10%) and children (20%) on renal replacement therapy have an inherited kidney disease (IKD). The new genomic era, ushered in by the next generation sequencing techniques, has contributed to the identification of new genes and facilitated the genetic diagnosis of the highly heterogeneous IKDs. Consequently, it has also allowed the reclassification of diseases and has broadened the phenotypic spectrum of many classical IKDs. Various genetic, epigenetic and environmental factors may explain 'atypical' phenotypes. In this article, we examine different mechanisms that may contribute to phenotypic variability and also provide case examples that illustrate them. The aim of the article is to raise awareness, among nephrologists and geneticists, of rare presentations that IKDs may show, to facilitate diagnosis.

Ambulatory blood pressure monitoring-derived short-term blood pressure variability is increased in Cushing's syndrome.

PubMed

Rebellato, Andrea; Grillo, Andrea; Dassie, Francesca; Sonino, Nicoletta; Maffei, Pietro; Martini, Chiara; Paoletta, Agostino; Fabris, Bruno; Carretta, Renzo; Fallo, Francesco

2014-11-01

Cushing's syndrome is associated with high cardiovascular morbility and mortality. Blood pressure (BP) variability within a 24-h period is increasingly recognized as an independent predictor of cardiovascular risk. The aim of our study was to investigate the short-term BP variability indices in Cushing's syndrome. Twenty-five patients with Cushing's syndrome (mean age 49 ± 13 years, 4 males; 21 Cushing's disease and 4 adrenal adenoma patients) underwent 24-h ambulatory BP monitoring (ABPM) and evaluation of cardiovascular risk factors. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 17 hypertensive (HYP-CUSH) patients and were compared with 20 normotensive (NOR-CTR) and 20 hypertensive (HYP-CTR) age-, sex-, and BMI-matched control subjects. Short-term BP variability was derived from ABPM and calculated as the following: (1) standard deviation (SD) of 24-h, daytime, and nighttime BP; (2) 24-h weighted SD of BP; and (3) average real variability (ARV), i.e., the average of the absolute differences between consecutive BP measurements over 24 h. In comparison with controls, patients with Cushing's syndrome, either normotensive or hypertensive, had higher 24-h and daytime SD of BP, as well as higher 24-h weighted SD and ARV of BP (P = 0.03 to P < 0.0001). No difference in metabolic parameters was observed between NOR-CTR and NOR-CUSH or between HYP-CTR and HYP-CUSH subgroups. ABPM-derived short-term BP variability is increased in Cushing's syndrome, independent of BP elevation. It may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in BP variability has to be further clarified.

Epstein-Barr Virus Latent Membrane Protein 1 Genetic Variability in Peripheral Blood B Cells and Oropharyngeal Fluids

PubMed Central

Renzette, Nicholas; Somasundaran, Mohan; Brewster, Frank; Coderre, James; Weiss, Eric R.; McManus, Margaret; Greenough, Thomas; Tabak, Barbara; Garber, Manuel; Kowalik, Timothy F.

2014-01-01

ABSTRACT We report the diversity of latent membrane protein 1 (LMP1) gene founder sequences and the level of Epstein-Barr virus (EBV) genome variability over time and across anatomic compartments by using virus genomes amplified directly from oropharyngeal wash specimens and peripheral blood B cells during acute infection and convalescence. The intrahost nucleotide variability of the founder virus was 0.02% across the region sequences, and diversity increased significantly over time in the oropharyngeal compartment (P = 0.004). The LMP1 region showing the greatest level of variability in both compartments, and over time, was concentrated within the functional carboxyl-terminal activating regions 2 and 3 (CTAR2 and CTAR3). Interestingly, a deletion in a proline-rich repeat region (amino acids 274 to 289) of EBV commonly reported in EBV sequenced from cancer specimens was not observed in acute infectious mononucleosis (AIM) patients. Taken together, these data highlight the diversity in circulating EBV genomes and its potential importance in disease pathogenesis and vaccine design. IMPORTANCE This study is among the first to leverage an improved high-throughput deep-sequencing methodology to investigate directly from patient samples the degree of diversity in Epstein-Barr virus (EBV) populations and the extent to which viral genome diversity develops over time in the infected host. Significant variability of circulating EBV latent membrane protein 1 (LMP1) gene sequences was observed between cellular and oral wash samples, and this variability increased over time in oral wash samples. The significance of EBV genetic diversity in transmission and disease pathogenesis are discussed. PMID:24429365

Epstein-Barr virus latent membrane protein 1 genetic variability in peripheral blood B cells and oropharyngeal fluids.

PubMed

Renzette, Nicholas; Somasundaran, Mohan; Brewster, Frank; Coderre, James; Weiss, Eric R; McManus, Margaret; Greenough, Thomas; Tabak, Barbara; Garber, Manuel; Kowalik, Timothy F; Luzuriaga, Katherine

2014-04-01

We report the diversity of latent membrane protein 1 (LMP1) gene founder sequences and the level of Epstein-Barr virus (EBV) genome variability over time and across anatomic compartments by using virus genomes amplified directly from oropharyngeal wash specimens and peripheral blood B cells during acute infection and convalescence. The intrahost nucleotide variability of the founder virus was 0.02% across the region sequences, and diversity increased significantly over time in the oropharyngeal compartment (P = 0.004). The LMP1 region showing the greatest level of variability in both compartments, and over time, was concentrated within the functional carboxyl-terminal activating regions 2 and 3 (CTAR2 and CTAR3). Interestingly, a deletion in a proline-rich repeat region (amino acids 274 to 289) of EBV commonly reported in EBV sequenced from cancer specimens was not observed in acute infectious mononucleosis (AIM) patients. Taken together, these data highlight the diversity in circulating EBV genomes and its potential importance in disease pathogenesis and vaccine design. This study is among the first to leverage an improved high-throughput deep-sequencing methodology to investigate directly from patient samples the degree of diversity in Epstein-Barr virus (EBV) populations and the extent to which viral genome diversity develops over time in the infected host. Significant variability of circulating EBV latent membrane protein 1 (LMP1) gene sequences was observed between cellular and oral wash samples, and this variability increased over time in oral wash samples. The significance of EBV genetic diversity in transmission and disease pathogenesis are discussed.

CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis.

PubMed

Rossi, Daniela; Volanti, Paolo; Brambilla, Liliana; Colletti, Tiziana; Spataro, Rossella; La Bella, Vincenzo

2018-03-01

Elevated cerebrospinal fluid (CSF), Neurofilament Light (NF-L) and phosphorylated Heavy (pNF-H) chain levels have been found in Amyotrophic Lateral Sclerosis (ALS), with studies reporting a correlation of both neurofilaments (NFs) with the disease progression. Here, we measured NF-L and pNF-H concentrations in the CSF of ALS patients from a single tertiary Center and investigated their relationship with disease-related variables. A total of 190 ALS patients (Bulbar, 29.9%; Spinal, 70.1%; M/F = 1.53) and 130 controls with mixed neurological diseases were recruited. Demographic and clinical variables were recorded, and ΔFS was used to rate the disease progression. Controls were divided into two cohorts: (1) patients with non-inflammatory neurological diseases (CTL-1); (2) patients with acute/subacute inflammatory diseases and tumors, expected to lead to significant axonal and tissue damage (CTL-2). For each patient and control, CSF was taken at the time of the diagnostic work-up and stored following the published guidelines. CSF NF-L and pNF-H were assayed with commercially available ELISA-based methods. Standard curves (from independent ELISA kits) were highly reproducible for both NFs, with a coefficient of variation < 20%. We found that CSF NF-L and pNF-H levels in ALS were significantly increased when compared to CTL-1 (NF-L: ALS, 4.7 ng/ml vs CTL-1, 0.61 ng/ml, p < 0.001; pNF-H: ALS, 1.7 ng/ml vs CTL-1, 0.03 ng/ml, p < 0.0001), but not to CTL-2. Analysis of different clinical and prognostic variables disclosed meaningful correlations with both NF-L and pNF-H levels. Our results, from a relatively large ALS cohort, confirm that CSF NF-L and pNF-H represent valuable diagnostic and prognostic biomarkers in ALS.

Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses’ Health Studies: a prospective cohort study

PubMed Central

2013-01-01

Background Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies. Methods Women in the Nurses’ Health Study and Nurses’ Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid. Results Over 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results. Conclusions Single measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated. PMID:24034517

Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses' Health Studies: a prospective cohort study.

PubMed

Townsend, Mary K; Franke, Adrian A; Li, Xingnan; Hu, Frank B; Eliassen, A Heather

2013-09-13

Associations of bisphenol A and phthalates with chronic disease health outcomes are increasingly being investigated in epidemiologic studies. The majority of previous studies of within-person variability in urinary bisphenol A and phthalate metabolite concentrations have focused on reproducibility over short time periods. Long-term reproducibility data are needed to assess the potential usefulness of these biomarkers for prospective studies, particularly those examining risk of diseases with long latency periods. Low within-person reproducibility may attenuate relative risk estimates and reduce statistical power to detect associations with disease. Therefore, we assessed within-person reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in spot urine samples over 1 to 3 years among women enrolled in two large cohort studies. Women in the Nurses' Health Study and Nurses' Health Study II provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for analyses of phthalic acid). To measure within-person reproducibility, we calculated Spearman rank correlation coefficients and intraclass correlation coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate metabolites, and phthalic acid. Over 1 to 3 years, within-person variability of bisphenol A was high relative to total variability (intraclass correlation coefficient = 0.14) and rankings of bisphenol A levels between time-points were weakly correlated (Spearman correlation = 0.19). Seven of the eight phthalate metabolites and phthalic acid demonstrated moderate within-person stability over time (Spearman correlation or intraclass correlation coefficient = 0.39-0.55). Restricting analyses to first-morning urine samples did not alter results. Single measurements of bisphenol A in spot urine samples were highly variable within women over 1 to 3 years, indicating that investigation of associations between a single urinary bisphenol A measurement and disease risk may be challenging in epidemiologic studies. The majority of urinary phthalate metabolites and phthalic acid appeared moderately reproducible within women over time, suggesting single measurements may be useful in epidemiologic studies, although observed relative risks can be substantially attenuated.

Relationship between the percentage of predicted cardiorespiratory fitness and cardiovascular disease risk factors in premenopausal women: a MONET study.

PubMed

Abdulnour, J; Boulay, P; Brochu, M; Rabasa-Lhoret, R; Yasari, S; Prud'homme, D

2010-08-01

To determine the relationships between the percentage predicted cardiorespiratory fitness (%CRF) and the anthropometric and metabolic cardiovascular disease risk factors in asymptomatic, premenopausal women. Data are baseline values obtained in 97 healthy premenopausal women (age 49.9 +/- 1.9 years; body mass index 23.2 +/- 2.2 kg/m(2)) participating in a longitudinal study from 2004 to 2009. The outcome measures were peak oxygen consumption (VO(2) peak), body mass index, body composition (percentage fat, fat mass, fat-free mass), waist circumference, abdominal subcutaneous fat, visceral fat, resting blood pressure and fasting lipids, glucose and insulin levels. The %CRF was negatively associated with body mass index, fat mass, percentage fat, waist circumference, abdominal subcutaneous fat, visceral fat, triglycerides, triglyceride/high density lipoprotein cholesterol, total cholesterol, total cholesterol/high density lipoprotein cholesterol, fasting insulin levels and HOMA-IR (- 0.59 < or = r < or = - 0.20; 0.01 < p < 0.05) and positively associated with insulin sensitivity index (r = 0.23; p < 0.05). VO(2) peak was associated with the same variables; however, correlations were slightly better (- 0.70 < or = r < or = 0.30; 0.01 < p < 0.05). Stepwise multiple regression analysis showed that %CRF was only independently correlated with plasma triglyceride levels. The results of this study suggest that %CRF was not a major predictor of anthropometric and metabolic variables associated with an increased risk of cardiovascular disease in asymptomatic premenopausal women. Finally, the VO(2) peak is a better predictor than the %CRF to assess the risk of cardiovascular disease in asymptomatic premenopausal women.

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

PubMed

Georgianos, Panagiotis I; Champidou, Eleni; Liakopoulos, Vassilios; Balaskas, Elias V; Zebekakis, Pantelis E

2018-04-01

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

Climate Predictors of the Spatial Distribution of Human Plague Cases in the West Nile Region of Uganda

PubMed Central

MacMillan, Katherine; Monaghan, Andrew J.; Apangu, Titus; Griffith, Kevin S.; Mead, Paul S.; Acayo, Sarah; Acidri, Rogers; Moore, Sean M.; Mpanga, Joseph Tendo; Enscore, Russel E.; Gage, Kenneth L.; Eisen, Rebecca J.

2012-01-01

East Africa has been identified as a region where vector-borne and zoonotic diseases are most likely to emerge or re-emerge and where morbidity and mortality from these diseases is significant. Understanding when and where humans are most likely to be exposed to vector-borne and zoonotic disease agents in this region can aid in targeting limited prevention and control resources. Often, spatial and temporal distributions of vectors and vector-borne disease agents are predictable based on climatic variables. However, because of coarse meteorological observation networks, appropriately scaled and accurate climate data are often lacking for Africa. Here, we use a recently developed 10-year gridded meteorological dataset from the Advanced Weather Research and Forecasting Model to identify climatic variables predictive of the spatial distribution of human plague cases in the West Nile region of Uganda. Our logistic regression model revealed that within high elevation sites (above 1,300 m), plague risk was positively associated with rainfall during the months of February, October, and November and negatively associated with rainfall during the month of June. These findings suggest that areas that receive increased but not continuous rainfall provide ecologically conducive conditions for Yersinia pestis transmission in this region. This study serves as a foundation for similar modeling efforts of other vector-borne and zoonotic disease in regions with sparse observational meteorologic networks. PMID:22403328

Modeling the spatial distribution of Chagas disease vectors using environmental variables and people´s knowledge.

PubMed

Hernández, Jaime; Núñez, Ignacia; Bacigalupo, Antonella; Cattan, Pedro E

2013-05-31

Chagas disease is caused by the protozoan Trypanosoma cruzi, which is transmitted to mammal hosts by triatomine insect vectors. The goal of this study was to model the spatial distribution of triatomine species in an endemic area. Vector's locations were obtained with a rural householders' survey. This information was combined with environmental data obtained from remote sensors, land use maps and topographic SRTM data, using the machine learning algorithm Random Forests to model species distribution. We analysed the combination of variables on three scales: 10 km, 5 km and 2.5 km cell size grids. The best estimation, explaining 46.2% of the triatomines spatial distribution, was obtained for 5 km of spatial resolution. Presence probability distribution increases from central Chile towards the north, tending to cover the central-coastal region and avoiding areas of the Andes range. The methodology presented here was useful to model the distribution of triatomines in an endemic area; it is best explained using 5 km of spatial resolution, and their presence increases in the northern part of the study area. This study's methodology can be replicated in other countries with Chagas disease or other vectorial transmitted diseases, and be used to locate high risk areas and to optimize resource allocation, for prevention and control of vectorial diseases.

Dispositional optimism, depression, disability and quality of life in Parkinson’s disease

PubMed Central

Gison, Annalisa; Dall’Armi, Valentina; Donati, Valentina; Rizza, Federica; Giaquinto, Salvatore

2014-01-01

Summary Very little research on dispositional optimism (DO) has been carried out in the field of Parkinson’s disease (PD). The present cross-sectional study, focusing on this personality trait, was performed with two main aims: i) to compare DO between patients with PD and a control group (CG); ii) to perform, in the PD group, a regression analysis including health-related variables, such as depression, anxiety, quality of life (QoL) and activities of daily living. Seventy PD participants and 70 healthy volunteers were enrolled in the study. The Mann-Whitney test was used to compare life orientation between the PD and CG groups. In the PD group, Pearson’s correlation analysis was used to investigate the relationship between the measures of DO and the other variables. Means of log-linear regression were also used. Mean ratios adjusted for sex, age, education, and severity of disease were estimated, with relative 95% confidence intervals and p-values. The main results were as follows: i) no significant difference in DO was found between the PD participants and the CG; ii) DO was positively associated with QoL and emotional distress and inversely correlated with the Unified Parkinson’s Disease Rating Scale; iii) DO was not correlated with disability. In conclusion, high DO predicts a satisfactory quality of life, low emotional distress and reduced disease severity in PD. PMID:25306121

Modeling the spatial distribution of Chagas disease vectors using environmental variables and people´s knowledge

PubMed Central

2013-01-01

Background Chagas disease is caused by the protozoan Trypanosoma cruzi, which is transmitted to mammal hosts by triatomine insect vectors. The goal of this study was to model the spatial distribution of triatomine species in an endemic area. Methods Vector’s locations were obtained with a rural householders’ survey. This information was combined with environmental data obtained from remote sensors, land use maps and topographic SRTM data, using the machine learning algorithm Random Forests to model species distribution. We analysed the combination of variables on three scales: 10 km, 5 km and 2.5 km cell size grids. Results The best estimation, explaining 46.2% of the triatomines spatial distribution, was obtained for 5 km of spatial resolution. Presence probability distribution increases from central Chile towards the north, tending to cover the central-coastal region and avoiding areas of the Andes range. Conclusions The methodology presented here was useful to model the distribution of triatomines in an endemic area; it is best explained using 5 km of spatial resolution, and their presence increases in the northern part of the study area. This study’s methodology can be replicated in other countries with Chagas disease or other vectorial transmitted diseases, and be used to locate high risk areas and to optimize resource allocation, for prevention and control of vectorial diseases. PMID:23724993

Characterization of the common bean host and Pseudocercospora griseola the causative agent of angular leaf spot disease in Tanzania

USDA-ARS?s Scientific Manuscript database

Angular leaf spot (ALS) caused by the fungus Pseudocercospora griseola is one of the most important diseases of common bean in Tanzania. Breeding for resistance to this disease is complicated by the variable nature of the pathogen. In Tanzania no thorough analysis of the variability of this pathogen...

Ambient soil cation exchange capacity inversely associates with infectious and parasitic disease risk in regional Australia.

PubMed

Liddicoat, Craig; Bi, Peng; Waycott, Michelle; Glover, John; Breed, Martin; Weinstein, Philip

2018-06-01

Human contact with soil may be important for building and maintaining normal healthy immune defence mechanisms, however this idea remains untested at the population-level. In this continent-wide, cross-sectional study we examine the possible public health benefit of ambient exposures to soil of high cation exchange capacity (CEC), a surrogate for potential immunomodulatory soil microbial diversity. We compare distributions of normalized mean 2011/12-2012/13 age-standardized public hospital admission rates (cumulative incidence) for infectious and parasitic diseases across regional Australia (representing an average of 29,516 patients/year in 228 local government areas), within tertiles of socioeconomic status and soil exposure. To test the significance of soil CEC, we use probabilistic individual-level environmental exposure data (with or without soil), and group-level variables, in robust non-parametric multilevel modelling to predict disease rates in unseen groups. Our results show that in socioeconomically-deprived areas with high CEC soils, rates of infectious and parasitic disease are significantly lower than areas with low CEC soils. Also, health inequality (relative risk) due to socioeconomic status is significantly lower in areas with high CEC soils compared to low CEC soils (Δ relative risk = 0.47; 95% CI: 0.13, 0.82). Including soil exposure when modelling rates of infectious and parasitic disease significantly improves prediction performance, explaining an additional 7.5% (Δ r 2  = 0.075; 95% CI: 0.05, 0.10) of variation in disease risk, in local government areas that were not used for model building. Our findings suggest that exposure to high CEC soils (typically high soil biodiversity) associates with reduced risk of infectious and parasitic diseases, particularly in lower socioeconomic areas. Copyright © 2018 Elsevier B.V. All rights reserved.

[Self-perception of disease in patients with chronic diseases].

PubMed

Adrián-Arrieta, L; Casas-Fernández de Tejerina, J M

2017-11-18

The aim of this study is to assess the self-perception of disease by patients with chronic diseases and determine factors related to their perception of disease. Cross-sectional descriptive study performed between September 2014 and April 2015 in nine (6 urban and 3 rural) Health Centres of Navarra, Spain. The participants were recruited by convenience sampling of 196 patients aged over 65 years with at least one chronic disease. The outcome variable was: Perception of disease evaluated through The Brief Illness Perception Questionnaire (9 items. Assessment of the cognitive and emotional representation of the disease. A higher total score indicates a greater threat of disease to the patient). Explanatory variables: Evaluation of the care received through the Patient Assessment of Chronic Illness Care, Katz index, Gijon's socio-family evaluation scale and quality of life using the EQ5D questionnaire. Other variables studied were: gender, age, education, Charlson index, and number of chronic diseases. The association between the total The Brief Illness Perception Questionnaire value and the rest of the variables was calculated. The self-perception of disease is more negative for a larger number of diseases (rho: 0.242; p=.001), greater patient dependence (rho: -0.193; P=.007), and a poorer self-perceived quality of life (EQ VAS rho: -0.484; P<.001. EQ5D5L Index value rho: -0.507; P<.001). The perception that chronic patients have about their disease worsens as their diseases and their dependence increase, and also worsens their quality of life. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

The Environmental Domain of Quality of Life in Patients with Chronic Respiratory Diseases.

PubMed

Kurpas, Donata; Szwamel, Katarzyna; Mroczek, Bożena

2016-01-01

The literature lacks reports on the role played by the Environmental domain of quality of life (QoL) in care for patients with chronic respiratory diseases. Such information has a high potential for implementation in modern medicine based on a 'tailor-made' holistic healthcare model. The purpose of this study was to determine the components that shape the Environmental domain of QoL in patients with chronic respiratory diseases. The study group consisted of 305 adult patients (median age 65 years) with at least one chronic respiratory disease. The greatest contribution to a high value of QoL in the Environmental domain among patients with chronic respiratory diseases was made by the coexistence of high QoL levels in other domains and in satisfaction with QoL. Programs for preventing a decline in QoL in the Environmental domain should include patients with low scores for the above variables as well as those with a low level of education, those who have not shown an improvement in their psychological well-being in the past 12 months, those with a low level of positive mental attitudes or healthy eating habits, a low Camberwell index, and low levels of overall pro-health behavior.

[Contraindications to succinylcholine in the intensive care unit. A prevalence study].

PubMed

Muñoz-Martínez, T; Garrido-Santos, I; Arévalo-Cerón, R; Rojas-Viguera, L; Cantera-Fernández, T; Pérez-González, R; Díaz-Garmendia, E

2015-03-01

To determine the prevalence of contraindications to succinylcholine in patients admitted to the ICU. An observational study was carried out, describing the frequency of succinylcholine contraindication by stays, and associating the contraindications to population variables. The adult general ICU of a reference hospital. Clinical-surgical critically ill patients. Thirty consecutive days were analyzed. None. Population variables: age, sex, APACHE II and SOFA scores, illness, days of hospitalization, mechanical ventilation and renal replacement therapy. hyperkalemia, bedridden patients, rhabdomyolysis, muscle trauma, burns, infusion of neuromuscular blocking agents, acute renal failure, chronic renal failure, intraocular hypertension, intracranial hypertension, statin use, malignant hyperthermia, neuromuscular disease, spinal cord sectioning, bradycardia < 50 bpm, succinylcholine allergy, and pseudo-cholinesterase deficiency. A total of 102 patients were admitted, aged 60 ± 16 years (56.9% males), with the generation of 657 stays. Main diseases: elective heart surgery (33%), respiratory failure (22%) and sepsis (14%). We documented 466 stays (70.9%) with contraindications, particularly bedridden patients (n=140), neuromuscular blocking agents (n=101), acute renal failure (n=126), statin use (n=167), neuromuscular disease (n=159) and bradycardia (n=76). We recorded 74 stays (11.3%) at high risk of complications, secondary to hyperkalemic risk associated to receptor dysregulation. A high risk of complications was associated to advanced age, prolonged hospitalization, prolonged length of stay in the ICU, higher APACHE II and SOFA scores, mechanical ventilation and renal replacement therapy. Given the high prevalence of contraindications to succinylcholine observed, we discourage its use in patients admitted to the ICU. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Prevalence, awareness, treatment, control, and risk factors of hypertension among adults: a cross-sectional study in Iran.

PubMed

Eghbali Babadi, Maryam; Khosravi, Alireza; Feizi, Awat; Mansouri, Asieh; Mahaki, Behzad; Sarrafzadegan, Nizal

2018-05-18

hypertension (HTN) is one of important risk factors of cardiovascular disease. Considering the importance of this disease for public health, this study was designed in order to determine the prevalence, awareness, treatment, control and risk factors of hypertension in Iranian adult population. This cross-sectional study was conducted on 2107 residents of Isfahan, Iran. Samples were selected through random, multistage, cluster sampling in 2015-2016. Outcome variable was hypertension determined by measuring right arm blood pressure via an arm digital blood pressure monitor. Awareness, treatment and control of HTN was assessed by a valid and reliable researcher-made questionnaire. Other demographic and clinical variables were assessed via a demographic questionnaire. The overall prevalence of hypertension was 17.3% (18.9% and 15.5% in men and women, respectively). The prevalence of hypertension increased in both genders with age. the prevalence of awareness of HTN among people with HTN was 69.2% of which 92.4% and 59.9% had drug treatment and controlled HTN, respectively. Logistic regression identified age, BMI, having diabetes and hyperlipidemia and positive family history of HTN as determinants of awareness of HTN. The results showed that hypertension is highly prevalent in the community, especially in men and in the middle-aged and older adults. Approximately 30% of patients are unaware of their disease, and there is less awareness among younger adults. Despite high frequency of drug treatment for hypertension, hypertension is uncontrolled in more than 40% of patients. Health policies should therefore consider appropriate preventive and therapeutic strategies for these high-risk groups.

Environmental variability and the transmission of haemorrhagic fever with renal syndrome in Changsha, People's Republic of China.

PubMed

Xiao, H; Gao, L D; Li, X J; Lin, X L; Dai, X Y; Zhu, P J; Chen, B Y; Zhang, X X; Zhao, J; Tian, H Y

2013-09-01

The transmission of haemorrhagic fever with renal syndrome (HFRS) is influenced by climatic, reservoir and environmental variables. The epidemiology of the disease was studied over a 6-year period in Changsha. Variables relating to climate, environment, rodent host distribution and disease occurrence were collected monthly and analysed using a time-series adjusted Poisson regression model. It was found that the density of the rodent host and multivariate El Niño Southern Oscillation index had the greatest effect on the transmission of HFRS with lags of 2–6 months. However, a number of climatic and environmental factors played important roles in affecting the density and transmission potential of the rodent host population. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.

A role of high impact weather events in waterborne disease outbreaks in Canada, 1975 - 2001.

PubMed

Thomas, Kate M; Charron, Dominique F; Waltner-Toews, David; Schuster, Corinne; Maarouf, Abdel R; Holt, John D

2006-06-01

Recent outbreaks of Escherichia coli O157:H7, Campylobacter, and Cryptosporidium have heightened awareness of risks associated with contaminated water supply. The objectives of this research were to describe the incidence and distribution of waterborne disease outbreaks in Canada in relation to preceding weather conditions and to test the association between high impact weather events and waterborne disease outbreaks. We examined extreme rainfall and spring snowmelt in association with 92 Canadian waterborne disease outbreaks between 1975 and 2001, using case-crossover methodology. Explanatory variables including accumulated rainfall, air temperature, and peak stream flow were used to determine the relationship between high impact weather events and the occurrence of waterborne disease outbreaks. Total maximum degree-days above 0 degrees C and accumulated rainfall percentile were associated with outbreak risk. For each degree-day above 0 degrees C the relative odds of an outbreak increased by a factor of 1.007 (95% confidence interval [CI] = 1.002 - 1.012). Accumulated rainfall percentile was dichotomized at the 93rd percentile. For rainfall events greater than the 93rd percentile the relative odds of an outbreak increased by a factor of 2.283 (95% [CI] = 1.216 - 4.285). These results suggest that warmer temperatures and extreme rainfall are contributing factors to waterborne disease outbreaks in Canada. This could have implications for water management and public health initiatives.

How the economic recession has changed the likelihood of reporting poor self-rated health in Spain.

PubMed

Arroyo, Elena; Renart, Gemma; Saez, Marc

2015-12-18

Between 2006 and 2011 self-rated health (SRH) (the subjective report of an individual's health status) actually improved in Spain despite its being in the grips of a serious economic recession. This study examines whether the likelihood of reporting poor health has changed because of the global financial crisis. It also attempts to estimate the differences between SRH and other self-perceived measures of health among groups before and during the current economic crisis in Spain. Cross-sectional population-based surveys were conducted in Spain (ENSE 2006 and ENSE 2011) and in Catalonia (ESCA 2006 and ESCA 2011) in 2006 and again in 2011. In this research work we have used random effects logistic models (dependent variable SRH 1 Poor, 0 Good) and exact matching and propensity score-matching. The results of the ENSE explanatory variables are the same in both 2006 and 2011. In other words, all diseases negatively affect SRH, whereas alcohol habits positively affect SRH and obesity is the only disease unrelated to SRH. ESCA explanatory variables' results show that in 2006 all diseases are significant and have large odds ratio (OR) and consequently those individuals suffering from any of these diseases are more likely to report poor health. In 2011 the same pattern follows with the exception of allergies, obesity, high cholesterol and hypertension, albeit they are not statistically significant. Drinking habits had a positive effect on SRH in 2006 and 2011, whereas smoking is considered as unrelated to SRH. The likelihood of reporting poor health in 2006 is added as a variable in with the logistic regression of 2011 and is not, in either the ENSE data or the ESCA data, significant. Furthermore, neither is it significant when controlling by age, gender, employment status or education. The results of our analysis show that the financial crisis did not alter the likelihood of reporting poor health in 2011. Therefore, there are no differences between our perceived health in either 2006 or in 2011.

REVIEW: High pressure NMR study of proteins - seeking roots for function, evolution, disease and food applications

NASA Astrophysics Data System (ADS)

Akasaka, Kazuyuki

2010-12-01

NMR experiments at variable pressure reveal a wide range of conformation of a globular protein spanning from within the folded ensemble to the fully unfolded ensemble, herewith collectively called "high-energy conformers". The observation of "high-energy conformers" in a wide variety of globular proteins has led to the "volume theorem": the partial molar volume of a protein decreases with the decrease in its conformational order. Since "high-energy conformers" are intrinsically more reactive than the basic folded conformer, they could play decisive roles in all phenomena of proteins, namely function, environmental adaptation and misfolding. Based on the information on high-energy conformers and the rules on their partial volume in its monomeric state and amyloidosis, one may have a general view on what is happening on proteins under pressure. Moreover, one may even choose a high-energy conformer of a protein with pressure as variable for a particular purpose. Bridging "high-energy conformers" to macroscopic pressure effects could be a key to success in pressure application to biology, medicine, food technology and industry in the near future.

267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation.

PubMed

Dopazo, Joaquín; Amadoz, Alicia; Bleda, Marta; Garcia-Alonso, Luz; Alemán, Alejandro; García-García, Francisco; Rodriguez, Juan A; Daub, Josephine T; Muntané, Gerard; Rueda, Antonio; Vela-Boza, Alicia; López-Domingo, Francisco J; Florido, Javier P; Arce, Pablo; Ruiz-Ferrer, Macarena; Méndez-Vidal, Cristina; Arnold, Todd E; Spleiss, Olivia; Alvarez-Tejado, Miguel; Navarro, Arcadi; Bhattacharya, Shomi S; Borrego, Salud; Santoyo-López, Javier; Antiñolo, Guillermo

2016-05-01

Recent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalog of local variability motivated the whole-exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one-third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including ∼10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes, and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies to distinguish real disease associations from population-specific polymorphisms. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Risk-based management of invading plant disease.

PubMed

Hyatt-Twynam, Samuel R; Parnell, Stephen; Stutt, Richard O J H; Gottwald, Tim R; Gilligan, Christopher A; Cunniffe, Nik J

2017-05-01

Effective control of plant disease remains a key challenge. Eradication attempts often involve removal of host plants within a certain radius of detection, targeting asymptomatic infection. Here we develop and test potentially more effective, epidemiologically motivated, control strategies, using a mathematical model previously fitted to the spread of citrus canker in Florida. We test risk-based control, which preferentially removes hosts expected to cause a high number of infections in the remaining host population. Removals then depend on past patterns of pathogen spread and host removal, which might be nontransparent to affected stakeholders. This motivates a variable radius strategy, which approximates risk-based control via removal radii that vary by location, but which are fixed in advance of any epidemic. Risk-based control outperforms variable radius control, which in turn outperforms constant radius removal. This result is robust to changes in disease spread parameters and initial patterns of susceptible host plants. However, efficiency degrades if epidemiological parameters are incorrectly characterised. Risk-based control including additional epidemiology can be used to improve disease management, but it requires good prior knowledge for optimal performance. This focuses attention on gaining maximal information from past epidemics, on understanding model transferability between locations and on adaptive management strategies that change over time. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Plus disease in retinopathy of prematurity: a continuous spectrum of vascular abnormality as basis of diagnostic variability

PubMed Central

Campbell, J. Peter; Kalpathy-Cramer, Jayashree; Erdogmus, Deniz; Tian, Peng; Kedarisetti, Dharanish; Moleta, Chace; Reynolds, James D.; Hutcheson, Kelly; Shapiro, Michael J.; Repka, Michael X.; Ferrone, Philip; Drenser, Kimberly; Horowitz, Jason; Sonmez, Kemal; Swan, Ryan; Ostmo, Susan; Jonas, Karyn E.; Chan, R.V. Paul; Chiang, Michael F.

2016-01-01

Objective To identify patterns of inter-expert discrepancy in plus disease diagnosis in retinopathy of prematurity (ROP). Design We developed two datasets of clinical images of varying disease severity (100 images and 34 images) as part of the Imaging and Informatics in ROP study, and determined a consensus reference standard diagnosis (RSD) for each image, based on 3 independent image graders and the clinical exam. We recruited 8 expert ROP clinicians to classify these images and compared the distribution of classifications between experts and the RSD. Subjects, Participants, and/or Controls Images obtained during routine ROP screening in neonatal intensive care units. 8 participating experts with >10 years of clinical ROP experience and >5 peer-reviewed ROP publications. Methods, Intervention, or Testing Expert classification of images of plus disease in ROP. Main Outcome Measures Inter-expert agreement (weighted kappa statistic), and agreement and bias on ordinal classification between experts (ANOVA) and the RSD (percent agreement). Results There was variable inter-expert agreement on diagnostic classifications between the 8 experts and the RSD (weighted kappa 0 – 0.75, mean 0.30). RSD agreement ranged from 80 – 94% agreement for the dataset of 100 images, and 29 – 79% for the dataset of 34 images. However, when images were ranked in order of disease severity (by average expert classification), the pattern of expert classification revealed a consistent systematic bias for each expert consistent with unique cut points for the diagnosis of plus disease and pre-plus disease. The two-way ANOVA model suggested a highly significant effect of both image and user on the average score (P<0.05, adjusted R2=0.82 for dataset A, and P< 0.05 and adjusted R2 =0.6615 for dataset B). Conclusions and Relevance There is wide variability in the classification of plus disease by ROP experts, which occurs because experts have different “cut-points” for the amounts of vascular abnormality required for presence of plus and pre-plus disease. This has important implications for research, teaching and patient care for ROP, and suggests that a continuous ROP plus disease severity score may more accurately reflect the behavior of expert ROP clinicians, and may better standardize classification in the future. PMID:27591053

Adherence and health literacy as related to outcome of patients treated for rheumatoid arthritis : Analyses of a large-scale observational study.

PubMed

Kuipers, J G; Koller, M; Zeman, F; Müller, K; Rüffer, J U

2018-04-24

Disabilities in daily living and quality of life are key endpoints for evaluating the treatment outcome for rheumatoid arthritis (RA). Factors possibly contributing to good outcome are adherence and health literacy. The survey included a representative nationwide sample of German rheumatologists and their patients with RA. The physician questionnaire included the disease activity score (DAS28) and medical prescriptions. The patient questionnaire included fatigue (EORTC QLQ-FA13), health assessment questionnaire (HAQ), quality of life (SF-12), health literacy (HELP), and patients' listings of their medications. Adherence was operationalized as follows: patient-reported (CQR5), behavioral (concordance between physicians' and patients' listings of medications), physician-assessed, and a combined measure of physician rating (1 = very adherent, 0 = less adherent) and the match between physicians' prescriptions and patients' accounts of their medications (1 = perfect match, 0 = no perfect match) that yielded three categories of adherence: high, medium, and low. Simple and multiple linear regressions (controlling for age, sex, smoking, drinking alcohol, and sport) were calculated using adherence and health literacy as predictor variables, and disease activity and patient-reported outcomes as dependent variables. 708 pairs of patient and physician questionnaires were analyzed. The mean patient age (73% women) was 60 years (SD = 12). Multiple regression analyses showed that high adherence was significantly associated with 5/7 outcome variables and health literacy with 7/7 outcome variables. Adherence and health literacy had weak but consistent effects on most outcomes. Thus, enhancing adherence and understanding of medical information could improve outcome, which should be investigated in future interventional studies.

Association between non-cholesterol sterol concentrations and Achilles tendon thickness in patients with genetic familial hypercholesterolemia.

PubMed

Baila-Rueda, Lucía; Lamiquiz-Moneo, Itziar; Jarauta, Estíbaliz; Mateo-Gallego, Rocío; Perez-Calahorra, Sofía; Marco-Benedí, Victoria; Bea, Ana M; Cenarro, Ana; Civeira, Fernando

2018-01-15

Familial hypercholesterolemia (FH) is a genetic disorder that result in abnormally high low-density lipoprotein cholesterol levels, markedly increased risk of coronary heart disease (CHD) and tendon xanthomas (TX). However, the clinical expression is highly variable. TX are present in other metabolic diseases that associate increased sterol concentration. If non-cholesterol sterols are involved in the development of TX in FH has not been analyzed. Clinical and biochemical characteristics, non-cholesterol sterols concentrations and Aquilles tendon thickness were determined in subjects with genetic FH with (n = 63) and without (n = 40) TX. Student-t test o Mann-Whitney test were used accordingly. Categorical variables were compared using a Chi square test. ANOVA and Kruskal-Wallis tests were performed to multiple independent variables comparison. Post hoc adjusted comparisons were performed with Bonferroni correction when applicable. Correlations of parameters in selected groups were calculated applying the non-parametric Spearman correlation procedure. To identify variables associated with Achilles tendon thickness changes, multiple linear regression were applied. Patients with TX presented higher concentrations of non-cholesterol sterols in plasma than patients without xanthomas (P = 0.006 and 0.034, respectively). Furthermore, there was a significant association between 5α-cholestanol, β-sitosterol, desmosterol, 24S-hydroxycholesterol and 27-hydroxycholesterol concentrations and Achilles tendon thickness (p = 0.002, 0.012, 0.020, 0.045 and 0.040, respectively). Our results indicate that non-cholesterol sterol concentrations are associated with the presence of TX. Since cholesterol and non-cholesterol sterols are present in the same lipoproteins, further studies would be needed to elucidate their potential role in the development of TX.

Clinical features and ryanodine receptor type 1 gene mutation analysis in a Chinese family with central core disease.

PubMed

Chang, Xingzhi; Jin, Yiwen; Zhao, Haijuan; Huang, Qionghui; Wang, Jingmin; Yuan, Yun; Han, Ying; Qin, Jiong

2013-03-01

Central core disease is a rare inherited neuromuscular disorder caused by mutations in ryanodine receptor type 1 gene. The clinical phenotype of the disease is highly variable. We report a Chinese pedigree with central core disease confirmed by the gene sequencing. All 3 patients in the family presented with mild proximal limb weakness. The serum level of creatine kinase was normal, and electromyography suggested myogenic changes. The histologic analysis of muscle biopsy showed identical central core lesions in almost all of the muscle fibers in the index case. Exon 90-106 in the C-terminal domain of the ryanodine receptor type 1 gene was amplified using polymerase chain reaction. One heterozygous missense mutation G14678A (Arg4893Gln) in exon 102 was identified in all 3 patients. This is the first report of a familial case of central core disease confirmed by molecular study in mainland China.

Idiopathic pulmonary fibrosis.

PubMed

Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María

2017-02-23

Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Experimental Evidence for Reduced Rodent Diversity Causing Increased Hantavirus Prevalence

PubMed Central

Suzán, Gerardo; Marcé, Erika; Giermakowski, J. Tomasz; Mills, James N.; Ceballos, Gerardo; Ostfeld, Richard S.; Armién, Blas; Pascale, Juan M.; Yates, Terry L.

2009-01-01

Emerging and re-emerging infectious diseases have become a major global environmental problem with important public health, economic, and political consequences. The etiologic agents of most emerging infectious diseases are zoonotic, and anthropogenic environmental changes that affect wildlife communities are increasingly implicated in disease emergence and spread. Although increased disease incidence has been correlated with biodiversity loss for several zoonoses, experimental tests in these systems are lacking. We manipulated small-mammal biodiversity by removing non-reservoir species in replicated field plots in Panama, where zoonotic hantaviruses are endemic. Both infection prevalence of hantaviruses in wild reservoir (rodent) populations and reservoir population density increased where small-mammal species diversity was reduced. Regardless of other variables that affect the prevalence of directly transmitted infections in natural communities, high biodiversity is important in reducing transmission of zoonotic pathogens among wildlife hosts. Our results have wide applications in both conservation biology and infectious disease management. PMID:19421313

Relationship of left ventricular hypertrophy and diastolic function with cardiovascular and renal outcomes in African Americans with hypertensive chronic kidney disease.

PubMed

Peterson, Gail E; de Backer, Tine; Contreras, Gabriel; Wang, Xuelei; Kendrick, Cynthia; Greene, Tom; Appel, Lawrence J; Randall, Otelio S; Lea, Janice; Smogorzewski, Miroslaw; Vagaonescu, Tudor; Phillips, Robert A

2013-09-01

African Americans with hypertension are at high risk for adverse outcomes from cardiovascular and renal disease. Patients with stage 3 or greater chronic kidney disease have a high prevalence of left ventricular (LV) hypertrophy and diastolic dysfunction. Our goal was to study prospectively the relationships of LV mass and diastolic function with subsequent cardiovascular and renal outcomes in the African American Study of Kidney Disease and Hypertension cohort study. Of 691 patients enrolled in the cohort, 578 had interpretable echocardiograms and complete relevant clinical data. Exposures were LV hypertrophy and diastolic parameters. Outcomes were cardiovascular events requiring hospitalization or causing death; a renal composite outcome of doubling of serum creatinine or end-stage renal disease (censoring death); and heart failure. We found strong independent relationships between LV hypertrophy and subsequent cardiovascular (hazard ratio, 1.16; 95% confidence interval, 1.05-1.27) events, but not renal outcomes. After adjustment for LV mass and clinical variables, lower systolic tissue Doppler velocities and diastolic parameters reflecting a less compliant LV (shorter deceleration time and abnormal E/A ratio) were significantly (P<0.05) associated with future heart failure events. This is the first study to show a strong relationship among LV hypertrophy, diastolic parameters, and adverse cardiac outcomes in African Americans with hypertension and chronic kidney disease. These echocardiographic risk factors may help identify high-risk patients with chronic kidney disease for aggressive therapeutic intervention.

Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

PubMed

Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Off-pump coronary surgery: surgical strategy for the high-risk patient.

PubMed

Van Belleghem, Y; Caes, F; Maene, L; Van Overbeke, H; Moerman, A; Van Nooten, G

2003-02-01

In a retrospective study, we compared two groups of consecutive patients operated by the same team during the year 2000 for coronary artery disease with the use of extracorporeal circulation (group 1, n=230) or on the beating heart using the Octopus II plus stabiliser (group 2, n=228). High-risk patients were identified by a EuroSCORE plus 6. EuroSCORE definitions and predicted risk models were utilized to compare the variables of the groups. There were no significant differences between the preoperative variables of the groups in age, gender, left ventricular function, diabetes and peripheral vascular and renal disease as is indicated by the Euroscore (resp. 4.7/5.1 p=0.107). Calcification of the ascending aorta and chronic obstructive lung disease were statistically significant more prevalent in the beating heart group. No differences in preoperative variables in the high-risk patients group (Euroscore 8.5/8.1 p=0.356) except for calcification of the ascending aorta. All patients underwent a full revascularisation through a midline sternotomy. Significant more distal anastomoses were performed in group 1 (3.7 per patient (1-6)) with regard to group 2 (2.9 per patient (1-6)). Anesthesia, postoperative treatment and follow up were equal for both groups. A significant lower incidence of atrial fibrillation (p=0.010), shorter ICU stay (p=0.031) and renal insufficiency (p=0.033) was reported in group 2. In the low risk group, we could not diagnose any difference between the two groups, except for atrial fibrillation. The benefits of the beating heart surgery however were more pronounced in the high-risk patient as is indicated by a significant reduction of the ICU stay by 1 day (3.5d/2.5d (p=0.028)), better preservation of the renal function (p=0.017) and a significant reduction of the length of hospital stay by more than two days (p=0.040). A lower incidence of atrial fibrillation, however not significant. In our experience, beating heart surgery is a safe alternative for conventional coronary heart surgery. High-risk patients do benefit most from this technique. It became our first choice in the elderly patient and patients presenting with higher co-morbidities.

[Application of variable magnetic fields in medicine--15 years experience].

PubMed

Sieroń, Aleksander; Cieślar, Grzegorz

2003-01-01

The results of 15-year own experimental and clinical research on application of variable magnetic fields in medicine were presented. In experimental studies analgesic effect (related to endogenous opioid system and nitrogen oxide activity) and regenerative effect of variable magnetic fields with therapeutical parameters was observed. The influence of this fields on enzymatic and hormonal activity, free oxygen radicals, carbohydrates, protein and lipid metabolism, dielectric and rheological properties of blood as well as behavioural reactions and activity of central dopamine receptor in experimental animals was proved. In clinical studies high therapeutic efficacy of magnetotherapy and magnetostimulation in the treatment of osteoarthrosis, abnormal ossification, osteoporosis, nasosinusitis, multiple sclerosis, Parkinson's disease, spastic paresis, diabetic polyneuropathy and retinopathy, vegetative neurosis, peptic ulcers, colon irritable and trophic ulcers was confirmed.

Range-wide genetic variability in Pacific madrone (Arbutus menziesii): examining disease resistance, growth, and survival in a common garden study

Treesearch

Marianne Elliott; Gary A. Chastagner; Gil Dermott; Alan Kanaskie; Richard A. Sniezko; Jim Hamlin

2012-01-01

Pacific madrone (Arbutus menziesii Pursh, Ericaceae) is an important evergreen hardwood species in Pacific Northwest (PNW) forests that provides food and habitat for wildlife and has high value in urban environments. Reeves (2007) indicates that Pacific madrone provides habitat for numerous wildlife species, especially cavity-nesting birds. Its...

Global mapping of highly pathogenic avian influenza H5N1 and H5Nx clade 2.3.4.4 viruses with spatial cross-validation

PubMed Central

Dhingra, Madhur S; Artois, Jean; Robinson, Timothy P; Linard, Catherine; Chaiban, Celia; Xenarios, Ioannis; Engler, Robin; Liechti, Robin; Kuznetsov, Dmitri; Xiao, Xiangming; Dobschuetz, Sophie Von; Claes, Filip; Newman, Scott H; Dauphin, Gwenaëlle; Gilbert, Marius

2016-01-01

Global disease suitability models are essential tools to inform surveillance systems and enable early detection. We present the first global suitability model of highly pathogenic avian influenza (HPAI) H5N1 and demonstrate that reliable predictions can be obtained at global scale. Best predictions are obtained using spatial predictor variables describing host distributions, rather than land use or eco-climatic spatial predictor variables, with a strong association with domestic duck and extensively raised chicken densities. Our results also support a more systematic use of spatial cross-validation in large-scale disease suitability modelling compared to standard random cross-validation that can lead to unreliable measure of extrapolation accuracy. A global suitability model of the H5 clade 2.3.4.4 viruses, a group of viruses that recently spread extensively in Asia and the US, shows in comparison a lower spatial extrapolation capacity than the HPAI H5N1 models, with a stronger association with intensively raised chicken densities and anthropogenic factors. DOI: http://dx.doi.org/10.7554/eLife.19571.001 PMID:27885988

Association of comorbid depression, anxiety, and stress disorders with Type 2 diabetes in Bahrain, a country with a very high prevalence of Type 2 diabetes.

PubMed

Almawi, W; Tamim, H; Al-Sayed, N; Arekat, M R; Al-Khateeb, G M; Baqer, A; Tutanji, H; Kamel, C

2008-11-01

This study examined the association of depression, anxiety, and stress with Type 2 diabetes (T2DM) in Bahrain, an island-country with a very high prevalence of T2DM. This was a cross-sectional study involving administering Depression Anxiety Stress Scales (DASS)-21 structured depression, anxiety, and stress scale to 143 T2DM patients and 132 healthy controls. Higher proportion of T2DM patients were found in the mild-moderate and severe- extremely severe depression (p=0.002), anxiety (p<0.001), and stress (p<0.001) groups. Chronic disease and disease duration were significantly associated with the 3 disturbances, while employment status was associated with anxiety and depression. Logistic regression analysis showed that anxiety, depression, and stress were associated with T2DM after adjusting for all variables, while age was the only significant variable associated with stress. These results suggest a positive contribution of T2DM to increased depressive and/or anxiety and/or stress disorders among the patients examined, thereby recommending counseling for T2DM patients.

Heart rate recovery and heart rate variability are unchanged in patients with coronary artery disease following 12 weeks of high-intensity interval and moderate-intensity endurance exercise training.

PubMed

Currie, Katharine D; Rosen, Lee M; Millar, Philip J; McKelvie, Robert S; MacDonald, Maureen J

2013-06-01

Decreased heart rate variability and attenuated heart rate recovery following exercise are associated with an increased risk of mortality in cardiac patients. This study investigated the effects of 12 weeks of moderate-intensity endurance exercise (END) and a novel low-volume high-intensity interval exercise protocol (HIT) on measures of heart rate recovery and heart rate variability in patients with coronary artery disease (CAD). Fourteen males with CAD participated in 12 weeks of END or HIT training, each consisting of 2 supervised exercise sessions per week. END consisted of 30-50 min of continuous cycling at 60% peak power output (PPO). HIT involved ten 1-min intervals at 88% PPO separated by 1-min intervals at 10% PPO. Heart rate recovery at 1 min and 2 min was measured before and after training (pre- and post-training, respectively) using a submaximal exercise bout. Resting time and spectral and nonlinear domain measures of heart rate variability were calculated. Following 12 weeks of END and HIT, there was no change in heart rate recovery at 1 min (END, 40 ± 12 beats·min(-1) vs. 37 ± 19 beats·min(-1); HIT, 31 ± 8 beats·min(-1) vs. 35 ± 8 beats·min(-1); p ≥ 0.05 for pre- vs. post-training) or 2 min (END, 44 ± 18 beats·min(-1) vs. 43 ± 19 beats·min(-1); HIT, 42 ± 10 beats·min(-1) vs. 50 ± 6 beats·min(-1); p ≥ 0.05 for pre- vs. post-training). All heart rate variability indices were unchanged following END and HIT training. In conclusion, neither END nor HIT exercise programs elicited training-induced improvements in cardiac autonomic function in patients with CAD. The absence of improvements with training may be attributed to the optimal medical management and normative pretraining state of our sample.

Controlling for high-density lipoprotein cholesterol does not affect the magnitude of the relationship between alcohol and coronary heart disease.

PubMed

Magnus, Per; Bakke, Eirin; Hoff, Dominic A; Høiseth, Gudrun; Graff-Iversen, Sidsel; Knudsen, Gun Peggy; Myhre, Ronny; Normann, Per Trygve; Næss, Øyvind; Tambs, Kristian; Thelle, Dag S; Mørland, Jørg

2011-11-22

This study tested the hypothesis that moderate alcohol intake exerts its cardioprotective effect mainly through an increase in the serum level of high-density lipoprotein cholesterol. In the Cohort of Norway (CONOR) study, 149 729 adult participants, recruited from 1994 to 2003, were followed by linkage to the Cause of Death Registry until 2006. At recruitment, questionnaire data on alcohol intake were collected, and the concentration of high-density lipoprotein cholesterol in serum was measured. Using Cox regression, we found that the adjusted hazard ratio for men for dying from coronary heart disease was 0.52 (95% confidence interval, 0.39-0.69) when consuming alcohol more than once a week compared with never or rarely. The ratio changed only slightly, to 0.55 (0.41-0.73), after the regression model included the serum level of high-density cholesterol. For women, the corresponding hazard ratios were 0.62 (0.32-1.23) and 0.68 (0.34-1.34), respectively. Alcohol intake is related to a reduced risk of death from coronary heart disease in the follow-up of a large, population-based Norwegian cohort study with extensive control for confounding factors. Our findings suggest that the serum level of high-density cholesterol is not an important intermediate variable in the possible causal pathway between moderate alcohol intake and coronary heart disease.

TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy.

PubMed

Fiorillo, Alyson A; Heier, Christopher R; Novak, James S; Tully, Christopher B; Brown, Kristy J; Uaesoontrachoon, Kitipong; Vila, Maria C; Ngheim, Peter P; Bello, Luca; Kornegay, Joe N; Angelini, Corrado; Partridge, Terence A; Nagaraju, Kanneboyina; Hoffman, Eric P

2015-09-08

The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dedifferentiated Chondrosarcoma of the Larynx.

PubMed

Fidai, Shiraz S; Ginat, Daniel T; Langerman, Alexander J; Cipriani, Nicole A

2016-09-01

Primary dedifferentiated chondrosarcoma occurring in the larynx is a rare head and neck malignancy. The cases reported in the literature suggest male gender predilection and variable clinical outcomes ranging from disease-free survival to disease-related death. Although a calcified matrix is suggestive of chondrosarcoma, the dedifferentiated component is not readily appreciated on conventional imaging modalities and thorough tissue sampling is necessary for confirming the diagnosis. Histologically, there is an abrupt transition from a well-differentiated chondrosarcoma to a high-grade spindle cell component, which can show focal heterologous differentiation. These features are exemplified in this sine qua non radiology-pathology correlation article.

The parasite that causes whirling disease, Myxobolus cerebralis, is genetically variable within and across spatial scales.

PubMed

Lodh, Nilanjan; Kerans, Billie L; Stevens, Lori

2012-01-01

Understanding the genetic structure of parasite populations on the natural landscape can reveal important aspects of disease ecology and epidemiology and can indicate parasite dispersal across the landscape. Myxobolus cerebralis (Myxozoa: Myxosporea), the causative agent of whirling disease in the definitive host Tubifex tubifex, is native to Eurasia and has spread to more than 25 states in the USA. The small amounts of data available to date suggest that M. cerebralis has little genetic variability. We examined the genetic variability of parasites infecting the definitive host T. tubifex in the Madison River, MT, and also from other parts of North America and Europe. We cloned and sequenced 18S ribosomal DNA and the internal transcribed spacer-1 (ITS-1) gene. Five oligochaetes were examined for 18S and five for ITS-1, only one individual was examined for both genes. We found two different 18S rRNA haplotypes of M. cerebralis from five worms and both intra- and interworm genetic variation for ITS-1, which showed 16 different haplotypes from among 20 clones. Comparison of our sequences with those from other studies revealed M. cerebralis from MT was similar to the parasite collected from Alaska, Oregon, California, and Virginia in the USA and from Munich, Germany, based on 18S, whereas parasite sequences from West Virginia were very different. Combined with the high haplotype diversity of ITS-1 and uniqueness of ITS-1 haplotypes, our results show that M. cerebralis is more variable than previously thought and raises the possibility of multiple introductions of the parasite into North America. © 2011 The Author(s) Journal of Eukaryotic Microbiology © 2011 International Society of Protistologists.

Programming and execution of movement in Parkinson's disease.

PubMed

Sheridan, M R; Flowers, K A; Hurrell, J

1987-10-01

Programming and execution of arm movements in Parkinson's disease were investigated in choice and simple reaction time (RT) situations in which subjects made aimed movements at a target. A no-aiming condition was also studied. Reaction time was fractionated using surface EMG recording into premotor (central) and motor (peripheral) components. Premotor RT was found to be greater for parkinsonian patients than normal age-matched controls in the simple RT condition, but not in the choice condition. This effect did not depend on the parameters of the impending movement. Thus, paradoxically, parkinsonian patients were not inherently slower at initiating aiming movements from the starting position, but seemed unable to use advance information concerning motor task demands to speed up movement initiation. For both groups, low velocity movements took longer to initiate than high velocity ones. In the no-aiming condition parkinsonian RTs were markedly shorter than when aiming, but were still significantly longer than control RTs. Motor RT was constant across all conditions and was not different for patient and control subjects. In all conditions, parkinsonian movements were around 37% slower than control movements, and their movement times were more variable, the differences showing up early on in the movement, that is, during the initial ballistic phase. The within-subject variability of movement endpoints was also greater in patients. The motor dysfunction displayed in Parkinson's disease involves a number of components: (1) a basic central problem with simply initiating movements, even when minimal programming is required (no-aiming condition); (2) difficulty in maintaining computed forces for motor programs over time (simple RT condition); (3) a basic slowness of movement (bradykinesia) in all conditions; and (4) increased variability of movement in both time and space, presumably caused by inherent variability in force production.

Additional value of anaerobic threshold in a general mortality prediction model in a urban patient cohort with Chagas cardiomyopathy.

PubMed

Silva, Roberto Ribeiro da; Reis, Michel Silva; Pereira, Basílio de Bragança; Nascimento, Emilia Matos do; Pedrosa, Roberto Coury

2017-12-01

Anaerobic threshold (AT) is recognized as objective and direct measurement that reflects variations in metabolism of skeletal muscles during exercise. Its prognostic value in heart diseases of non-chagasic etiology is well established. However, the assessment of risk of death in Chagas heart disease is relatively well established by Rassi score. But, the added value that AT can bring to Rassi score has not been studied yet. To assess whether AT presents additional effect to Rassi score in patients with chronic Chagas' heart disease. Prospective research of dynamic cohort by review of 150 medical records of patients. Were selected for cohort 45 medical records of patients who underwent cardiopulmonary exercise testing between 1996-1997 and followed until September 2015. Data analysis to detect association between studied variables can be seen using a logistic regression model. The suitability of the models was verified using ROC curves and the coefficient of determination R 2 . 8 patients (17.78%) died by September 2015, with 7 of them (87.5%) from cardiovascular causes, of which 4 (57.14%) were considered on high risk by Rassi score. With Rassi score as independent variable, and death being the outcome, we obtained an area under the curve (AUC)=0.711, with R 2 =0.214. Instituting AT as independent variable, we found AUC=0.706, with R 2 =0.078. When we define Rassi score and AT as independent variables, it was obtained AUC=0.800 and R 2 =0.263. when AT is included in logistic regression, it increases by 5% the explanation (R 2 ) to the death estimation. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Forecasting disease risk for increased epidemic preparedness in public health

NASA Technical Reports Server (NTRS)

Myers, M. F.; Rogers, D. J.; Cox, J.; Flahault, A.; Hay, S. I.

2000-01-01

Emerging infectious diseases pose a growing threat to human populations. Many of the world's epidemic diseases (particularly those transmitted by intermediate hosts) are known to be highly sensitive to long-term changes in climate and short-term fluctuations in the weather. The application of environmental data to the study of disease offers the capability to demonstrate vector-environment relationships and potentially forecast the risk of disease outbreaks or epidemics. Accurate disease forecasting models would markedly improve epidemic prevention and control capabilities. This chapter examines the potential for epidemic forecasting and discusses the issues associated with the development of global networks for surveillance and prediction. Existing global systems for epidemic preparedness focus on disease surveillance using either expert knowledge or statistical modelling of disease activity and thresholds to identify times and areas of risk. Predictive health information systems would use monitored environmental variables, linked to a disease system, to be observed and provide prior information of outbreaks. The components and varieties of forecasting systems are discussed with selected examples, along with issues relating to further development.

Forecasting Disease Risk for Increased Epidemic Preparedness in Public Health

PubMed Central

Myers, M.F.; Rogers, D.J.; Cox, J.; Flahault, A.; Hay, S.I.

2011-01-01

Emerging infectious diseases pose a growing threat to human populations. Many of the world’s epidemic diseases (particularly those transmitted by intermediate hosts) are known to be highly sensitive to long-term changes in climate and short-term fluctuations in the weather. The application of environmental data to the study of disease offers the capability to demonstrate vector–environment relationships and potentially forecast the risk of disease outbreaks or epidemics. Accurate disease forecasting models would markedly improve epidemic prevention and control capabilities. This chapter examines the potential for epidemic forecasting and discusses the issues associated with the development of global networks for surveillance and prediction. Existing global systems for epidemic preparedness focus on disease surveillance using either expert knowledge or statistical modelling of disease activity and thresholds to identify times and areas of risk. Predictive health information systems would use monitored environmental variables, linked to a disease system, to be observed and provide prior information of outbreaks. The components and varieties of forecasting systems are discussed with selected examples, along with issues relating to further development. PMID:10997211

Glaucoma Structural and Functional Progression in American and Korean Cohorts

PubMed Central

Kostanyan, Tigran; Sung, Kyung Rim; Schuman, Joel S.; Ling, Yun; Lucy, Katie A.; Bilonick, Richard A.; Ishikawa, Hiroshi; Kagemann, Larry; Lee, Jin Y.; Wollstein, Gadi

2016-01-01

Objective To compare the rate of glaucoma structural and functional progression in American and Korean cohorts. Design Retrospective longitudinal study. Participants 313 eyes from 189 glaucoma and glaucoma suspects, followed for an average of 38 months. Methods All subjects were examined semiannually with visual field (VF) testing and spectral-domain optical coherence tomography. All subjects had ≥5 reliable visits. Main Outcome Measurements The rates of change of retinal nerve fiber layer (RNFL) thickness, cup-to-disc (C/D) ratios, and VF mean deviation (MD) were compared between the cohorts. Variables affecting the rate of change for each parameter were determined, including ethnicity, refraction, baseline age and severity, disease subtype (high vs. normal tension glaucoma), clinical diagnosis (glaucoma vs. glaucoma suspect), and the interactions between variables. Results The Korean cohort was predominantly normal tension glaucoma, while the American cohort was high tension glaucoma. Cohorts had similar VF parameters at baseline, but the Korean eyes had significantly thinner mean RNFL and larger cups. Korean glaucoma eyes showed a faster thinning of mean RNFL (mean: −0.71 vs. −0.24μm/year, p<0.01). There was no detectable difference in the rate of change between the glaucoma cohorts for C/D ratios and VF MD and for all parameters in glaucoma suspect eyes. Different combinations of the tested variables significantly impacted the rate of change. Conclusion Ethnicity, baseline severity, disease subtype, and clinical diagnosis should be considered when comparing glaucoma progression studies. PMID:26778345

Impact of temperature variability on childhood hand, foot and mouth disease in Huainan, China.

PubMed

Xu, J; Zhao, D; Su, H; Xie, M; Cheng, J; Wang, X; Li, K; Yang, H; Wen, L; Wang, B

2016-05-01

The short-term temperature variation has been shown to be significantly associated with human health. However, little is known about whether temperature change between neighbouring days (TCN) and diurnal temperature range (DTR) have any effect on childhood hand, foot and mouth disease (HFMD). This study aims to explore whether temperature variability has any effect on childhood HFMD. Ecological study. The association between meteorological variables and HFMD cases in Huainan, China, from January 1st 2012 to December 31st 2014 was analysed using Poisson generalized linear regression combined with distributed lag non-linear model (DLNM) after controlling for long-term trend and seasonality, mean temperature and relative humidity. An adverse effect of TCN on childhood HFMD was observed, and the impact of TCN was the greatest at five days lag, with a 10% (95% CI: 4%-15%) increase of daily number of HFMD cases per 3 °C (10th percentile) decrease of TCN. Male children, children aged 0-5 years, scattered children and children in high-risk areas appeared to be more vulnerable to the TCN effect than others. However, there was no significant association between DTR and childhood HFMD. Our findings indicate that TCN drops may increase the incidence of childhood HFMD in Huainan, highlighting the importance of protecting children from forthcoming TCN drops, particularly for those who are male, young, scattered and from high-risk areas. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

[A study on the thermographic diagnosis of vibration disease of tie-tamper operators in the Japanese National Railways].

PubMed

Hirahata, H

1984-01-01

There have been many studies of thermographic diagnosis of vibration disease, but few of them seem to have discussed tie-tamping machines as a cause. This study focuses on thermographic diagnosis of vibration disease in tie-tamper operators of the Japanese National Railways. In the diagnosis the subject's both hands were immersed in water at 10 degrees C for 3 minutes before being examined. Variables such as season, age, type of vibration tool used and total operating time were considered. These were selected as outside variables and thermographic results as dependent variables, in Quantification Method II. Season and confirmation of vibration disease were found to have a relationship to thermographic scaling, but no such relationship was found for age, type of vibration tool used, or total operating time. A cross-analysis of variables confirmed the relationship with season, and revealed that there were fewer confirmed cases of vibration disease in spring and summer than in fall and winter. It was finally concluded that thermographic analysis is more reliable in colder weather.

The validity of the Gait Variability Index for individuals with mild to moderate Parkinson's disease.

PubMed

Rennie, Linda; Dietrichs, Espen; Moe-Nilssen, Rolf; Opheim, Arve; Franzén, Erika

2017-05-01

Increased step-to-step variability is a feature of gait in individuals with Parkinson's disease (PD) and is associated with increased disease severity and reductions in balance and mobility. The Gait Variability Index (GVI) quantifies gait variability in spatiotemporal variables where a score ≥100 indicates a similar level of gait variability as the control group, and lower scores denote increased gait variability. The study aim was to explore mean GVI score and investigate construct validity of the index for individuals with mild to moderate PD. 100 (57 males) subjects with idiopathic PD, Hoehn & Yahr 2 (n=44) and 3, and ≥60 years were included. Data on disease severity, dynamic balance, mobility and spatiotemporal gait parameters at self-selected speed (GAITRite) was collected. The results showed a mean overall GVI: 97.5 (SD 11.7) and mean GVI for the most affected side: 94.5 (SD 10.6). The associations between the GVI and Mini- BESTest and TUG were low (r=0.33 and 0.42) and the GVI could not distinguish between Hoehn & Yahr 2 and 3 (AUC=0.529, SE=0.058, p=0.622). The mean GVI was similar to previously reported values for older adults, contrary to consistent reports of increased gait variability in PD compared to healthy peers. Therefore, the validity of the GVI could not be confirmed for individuals with mild to moderate PD in its current form due to low associations with validated tests for functional balance and mobility and poor discriminatory ability. Future work should aim to establish which spatiotemporal variables are most informative regarding gait variability in individuals with PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Sparse PLS discriminant analysis: biologically relevant feature selection and graphical displays for multiclass problems.

PubMed

Lê Cao, Kim-Anh; Boitard, Simon; Besse, Philippe

2011-06-22

Variable selection on high throughput biological data, such as gene expression or single nucleotide polymorphisms (SNPs), becomes inevitable to select relevant information and, therefore, to better characterize diseases or assess genetic structure. There are different ways to perform variable selection in large data sets. Statistical tests are commonly used to identify differentially expressed features for explanatory purposes, whereas Machine Learning wrapper approaches can be used for predictive purposes. In the case of multiple highly correlated variables, another option is to use multivariate exploratory approaches to give more insight into cell biology, biological pathways or complex traits. A simple extension of a sparse PLS exploratory approach is proposed to perform variable selection in a multiclass classification framework. sPLS-DA has a classification performance similar to other wrapper or sparse discriminant analysis approaches on public microarray and SNP data sets. More importantly, sPLS-DA is clearly competitive in terms of computational efficiency and superior in terms of interpretability of the results via valuable graphical outputs. sPLS-DA is available in the R package mixOmics, which is dedicated to the analysis of large biological data sets.

Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel

PubMed Central

Jiang, Xi-Ling; Samant, Snehal; Lesko, Lawrence J.; Schmidt, Stephan

2017-01-01

Acute coronary syndromes (ACS) remain life-threatening disorders that are associated with high morbidity and mortality. Dual-antiplatelet therapy with aspirin and clopidogrel has shown to reduce cardiovascular events in patients with ACS. However, there is substantial inter-individual variability in response to clopidogrel treatment in addition to prolonged recovery of platelet reactivity as a result of irreversible binding to P2Y12 receptors. This high inter-individual variability in treatment response has primarily been associated with genetic polymorphisms in the genes encoding for cytochrome (CYP) 2C19 that affect clopidogrel’s pharmacokinetics. While FDA has issued a boxed warning for CYP2C19 poor metabolizers due to a potentially reduced efficacy in these patients, results from multivariate analyses suggest that additional factors, including age, sex, obesity, concurrent diseases and drug-drug interactions, may all contribute to the overall between-subject variability in treatment response. However, the extent to which each of these factors contributes to the overall variability and how they are interrelated is currently unclear. The objective of this review article is to provide a comprehensive update on the different factors that influence clopidogrel’s pharmacokinetics and pharmacodynamics and how they mechanistically contribute to inter-individual differences in response to clopidogrel treatment. PMID:25559342

Day-by-Day Variability of Home Blood Pressure and Incident Cardiovascular Disease in Clinical Practice: The J-HOP Study (Japan Morning Surge-Home Blood Pressure).

PubMed

Hoshide, Satoshi; Yano, Yuichiro; Mizuno, Hiroyuki; Kanegae, Hiroshi; Kario, Kazuomi

2018-01-01

We assessed the relationship between day-by-day home blood pressure (BP) variability and incident cardiovascular disease (CVD) in clinical practice. J-HOP study (Japan Morning Surge-Home Blood Pressure) participants underwent home BP monitoring in the morning and evening for a 14-day period, and their BP levels and BP variability independent of the mean (VIM) were assessed. Incident CVD events included coronary heart disease and stroke. Cox models were fitted to assess the home BP variability-CVD risk association. Among 4231 participants (mean±SD age, 64.9±10.9 years; 53.3% women; 79.1% taking antihypertensive medication), mean (SD) home systolic BP (SBP) levels over time and VIM SBP were 134.2 (14.3) and 6.8 (2.5) mm Hg, respectively. During a 4-year follow-up period (16 750.3 person-years), 148 CVD events occurred. VIM SBP was associated with CVD risk (hazard ratio per 1-SD increase, 1.32; 95% confidence interval [CI], 1.15-1.52), independently of mean home SBP levels over time and circulating B-type natriuretic peptide levels or urine albumin-to-creatinine ratio. Adding VIM SBP to the CVD prediction model improved the discrimination (C statistic, 0.785 versus 0.770; C statistic difference, 0.015; 95% CI, 0.003-0.028). Changes in continuous net reclassification improvement (0.259; 95% CI, 0.052-0.537), absolute integrated discrimination improvement (0.010; 95% CI, 0.003-0.016), and relative integrated discrimination improvement (0.104; 95% CI, 0.037-0.166) were also observed with the addition of VIM SBP to the CVD prediction models. In addition to the assessments of mean home SBP levels and cardiovascular end-organ damage, home BP variability measurements may provide a clinically useful distinction between high- and low-risk groups among Japanese outpatients. © 2017 American Heart Association, Inc.

Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non-muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review.

PubMed

Soukup, Viktor; Čapoun, Otakar; Cohen, Daniel; Hernández, Virginia; Babjuk, Marek; Burger, Max; Compérat, Eva; Gontero, Paolo; Lam, Thomas; MacLennan, Steven; Mostafid, A Hugh; Palou, Joan; van Rhijn, Bas W G; Rouprêt, Morgan; Shariat, Shahrokh F; Sylvester, Richard; Yuan, Yuhong; Zigeuner, Richard

2017-11-01

Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. This article summarises the utility of two different grading systems for non-muscle-invasive bladder cancer. Both systems predict progression and recurrence, although pathologists vary in their reporting; suggestions for further improvements are made. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Asymptomatic peripheral artery disease can limit maximal exercise capacity in chronic obstructive pulmonary disease patients regardless of airflow obstruction and lung hyperinflation.

PubMed

Crisafulli, Ernesto; Scelfo, Chiara; Tzani, Panagiota; Aiello, Marina; Bertorelli, Giuseppina; Chetta, Alfredo

2017-06-01

Background Silent/asymptomatic peripheral artery disease may occur in patients with chronic obstructive pulmonary disease, but it is poorly investigated. The primary aim of this study was to evaluate in chronic obstructive pulmonary disease patients the impact of asymptomatic/silent peripheral artery disease on maximal exercise capacity; the secondary aim was to search for predictors of peripheral artery disease. Methods We prospectively enrolled chronic obstructive pulmonary disease outpatients. Data on anthropometric characteristics, lung function, cardiopulmonary exercise test and ankle-brachial index were recorded. The cut-off of ankle-brachial index used to define patients with peripheral artery disease was ≤0.90. Results We studied 47 patients and found 24 patients (51%) who showed peripheral artery disease. As compared to patients without peripheral artery disease, patients with peripheral artery disease had lower values of peak oxygen uptake, peak workload, energy expenditure (metabolic equivalents) and heart rate recovery, but showed the same degree of airflow obstruction and static and dynamic hyperinflation. In a multivariate linear regression model performed to identify variables predicting metabolic equivalents, ankle-brachial index (β 2.59; 95% confidence interval 0.51-4.67; p = 0.016) was an independent variable. In the search for predictors of peripheral artery disease, heart rate recovery (odds ratio 8.80; 95% confidence interval 1.30-59.35; p = 0.026) increased the risk of peripheral artery disease, whereas metabolic equivalents (odds ratio 0.50; 95% confidence interval 0.26-0.94, p = 0.033) and inhaled corticosteroids+long-acting β 2 agonists (odds ratio 0.13; 95% confidence interval 0.02-0.83; p = 0.030) reduced this risk. Conclusions In chronic obstructive pulmonary disease outpatients, asymptomatic/silent peripheral artery disease affects the maximal exercise capacity regardless of airflow obstruction and lung hyperinflation. A delay of heart rate recovery increase the risk of peripheral artery disease, whereas high values of metabolic equivalents and the use of inhaled corticosteroids+long-acting β 2 agonists reduces this risk.

Variations in non-prescription drug consumption and expenditure: Determinants and policy implications.

PubMed

Otto, Monica; Armeni, Patrizio; Jommi, Claudio

2018-01-31

This paper analyses the determinants of cross-regional variations in expenditure and consumption for non-prescription drugs using the Italian Health Care Service as a case study. This research question has never been posed in other literature contributions. Per capita income, the incidence of elderly people, the presence of distribution points alternative to community pharmacies (para-pharmacies and drug corners in supermarkets), and the disease prevalence were included as possible explanatory variables. A trade-off between consumption of non-prescription and prescription-only drugs was also investigated. Correlation was tested through linear regression models with regional fixed-effects. Demand-driven variables, including the prevalence of the target diseases and income, were found to be more influential than supply-side variables, such as the presence of alternative distribution points. Hence, the consumption of non-prescription drugs appears to respond to needs and is not induced by the supply. The expected trade-off between consumption for prescription-only and non-prescription drugs was not empirically found: increasing the use of non-prescription drugs did not automatically imply savings on prescription-only drugs covered by third payers. Despite some caveats (the short period of time covered by the longitudinal data and some missing monthly data), the regression model revealed a high explanatory power of the variability and a strong predictive ability of future values. Copyright © 2018 Elsevier B.V. All rights reserved.

Young Age at Diagnosis of Type 1 Diabetes Is Associated with the Development of Celiac Disease-Associated Antibodies in Children Living in Newfoundland and Labrador, Canada.

PubMed

Pall, Harpreet; Newhook, Leigh A; Aaron, Hillary; Curtis, Joseph; Randell, Ed

2015-10-14

The objectives of this study were to establish the prevalence of positive antibodies to endomysium (EMA) and tissue transglutaminase (tTG) in children with type 1 diabetes living in Newfoundland and Labrador (NL), and to examine clinical features associated with positive antibodies. Patients were recruited from the pediatric diabetes clinic. One hundred sixty-seven children with type 1 diabetes from the 280 children followed at the clinic were prospectively screened for celiac disease using EMA and tTG. The variables of Irish descent, age at onset of diabetes, duration of diabetes, sex, family history of celiac disease, hemoglobin A1C (A1C), ferritin, gastrointestinal symptoms, and body mass index were compiled for all patients. The group of patients with positive antibodies to EMA and/or tTG was compared to the group with negative antibodies. The prevalence of patients with positive antibodies to EMA and/or tTG was 16.8% (n = 28). One patient had also been previously diagnosed with symptomatic celiac disease. The two statistically significant variables with positive antibodies were an earlier age at onset of diabetes (Mann-Whitney U two-tailed test: mean difference 3.2 years, 95% CI 1.7-4.8 years, p < 0.0001) and longer duration of diabetes (Mann-Whitney U two-tailed test: mean difference 2.9 years, 95% CI 1.3-4.4 years, p < 0.0001). Irish descent was associated with positive antibodies but did not reach statistical significance. On logistic regression analysis performed with these three variables together, only age at onset of diabetes remained significant. There is a high prevalence of celiac disease-associated antibodies in children living in NL with type 1 diabetes. Unlike other clinical features, an earlier age at onset of diabetes was predictive for positive antibodies. As the majority of children with positive antibodies did not have signs or symptoms of celiac disease, routine screening for celiac disease in type 1 diabetes is recommended.

Association between climate factors and diarrhoea in a Mekong Delta area

NASA Astrophysics Data System (ADS)

Phung, Dung; Huang, Cunrui; Rutherford, Shannon; Chu, Cordia; Wang, Xiaoming; Nguyen, Minh; Nguyen, Nga Huy; Manh, Cuong Do; Nguyen, Trung Hieu

2015-09-01

The Mekong Delta is vulnerable to changes in climate and hydrological events which alter environmental conditions, resulting in increased risk of waterborne diseases. Research exploring the association between climate factors and diarrhoea, the most frequent waterborne disease in Mekong Delta region, is sparse. This study evaluated the climate-diarrhoea association in Can Tho city, a typical Mekong Delta area in Vietnam. Climate data (temperature, relative humidity, and rainfall) were obtained from the Southern Regional Hydro-Meteorological Centre, and weekly counts of diarrhoea visits were obtained from Can Tho Preventive Medicine Centre from 2004 to 2011. Analysis of climate and health variables was carried out using spline function to adjust for seasonal and long-term trends of variables. A distributed lag model was used to investigate possible delayed effects of climate variables on diarrhoea (considering 0-4 week lag periods), then the multivariate Poisson regression was used to examine any potential association between climate factors and diarrhoea. The results indicated that the diarrhoea incidence peaked within the period August-October annually. Significant positive associations were found between increased diarrhoea and high temperature at 4 weeks prior to the date of hospital visits (IRR = 1.07; 95 % CI = 1.04-1.08), high relative humidity (IRR = 1.13; 95 % CI = 1.12-1.15) and high (>90th percentile) cumulative rainfall (IRR = 1.05; 95 % CI = 1.05-1.08). The association between climate factors and diarrhoea was stronger in rural than urban areas. These findings in the context of the projected changes of climate conditions suggest that climate change will have important implications for residential health in Mekong Delta region.

High interpatient variability of treosulfan exposure is associated with early toxicity in paediatric HSCT: a prospective multicentre study.

PubMed

van der Stoep, M Y Eileen C; Bertaina, Alice; Ten Brink, Marloes H; Bredius, Robbert G; Smiers, Frans J; Wanders, Dominique C M; Moes, Dirk Jan A R; Locatelli, Franco; Guchelaar, Henk-Jan; Zwaveling, Juliëtte; Lankester, Arjan C

2017-12-01

Treosulfan-based conditioning is increasingly employed in paediatric haematopoietic stem cell transplantation (HSCT). Data on treosulfan pharmacokinetics in children are scarce, and the relationship between treosulfan exposure, toxicity and clinical outcome is unresolved. In this multicentre prospective observational study, we studied treosulfan pharmacokinetics and the drug's relationship with regimen-related toxicity and early clinical outcome in 77 paediatric patients. Treosulfan dose was 30 g/m 2 , administered over 3 consecutive days in infants <1 year old (n = 12) and 42 g/m 2 in children ≥1 year old (n = 65). Mean day 1 treosulfan exposure was 1744 ± 795 mg*h/l (10 g/m 2 ) and 1561 ± 511 mg*h/l (14 g/m 2 ), with an inter-individual variability of 56 and 33% in the respective groups. High treosulfan exposure (>1650 mg*h/l) was associated with an increased risk of mucosal [Odds ratio (OR) 4·40; 95% confidence interval (CI) 1·19-16·28, P = 0·026] and skin toxicity (OR 4·51; 95% CI 1·07-18·93, P = 0·040). No correlation was found between treosulfan exposure and the early clinical outcome parameters: engraftment, acute graft-versus-host disease and donor chimerism. Our study provides the first evidence in a large cohort of paediatric patients of high variability in treosulfan pharmacokinetics and an association between treosulfan exposure and early toxicity. Ongoing studies will reveal whether treosulfan exposure is related to long-term disease-specific outcome and late treatment-related toxicity. © 2017 John Wiley & Sons Ltd.

Clinical and Microbiological Features of HIV-Associated Tuberculous Meningitis in Vietnamese Adults

PubMed Central

Torok, M. Estee; Chau, Tran Thi Hong; Mai, Pham Phuong; Phong, Nguyen Duy; Dung, Nguyen Thi; Chuong, Ly Van; Lee, Sue J.; Caws, M.; de Jong, Menno D.; Hien, Tran Tinh; Farrar, Jeremy J.

2008-01-01

Methods The aim of this prospective, observational cohort study was to determine the clinical and microbiological features, outcome, and baseline variables predictive of death, in Vietnamese adults with HIV-associated tuberculous meningitis (TBM). 58 patients were admitted to the Hospital for Tropical Diseases in Ho Chi Minh City and underwent routine clinical and laboratory assessments. Treatment was with standard antituberculous therapy and adjunctive dexamethasone; antiretroviral therapy was not routinely available. Patients were followed up until the end of TB treatment or death. Results The median symptom duration was 11 days (range 2–90 days), 21.8% had a past history of TB, and 41.4% had severe (grade 3) TBM. The median CD4 count was 32 cells/mm3. CSF findings were as follows: median leucocyte count 438×109cells/l (63% neutrophils), 69% smear positive and 87.9% culture positive. TB drug resistance rates were high (13% mono-resistance 32.6% poly-resistance 8.7% multidrug resistance). 17% patients developed further AIDS-defining illnesses. 67.2% died (median time to death 20 days). Three baseline variables were predictive of death by multivariate analysis: increased TBM grade [adjusted hazard ratio (AHR) 1.73, 95% CI 1.08–2.76, p = 0.02], lower serum sodium (AHR 0.93, 95% CI 0.89 to 0.98, p = 0.002) and decreased CSF lymphocyte percentage (AHR 0.98, 95% CI 0.97 to 0.99, p = 0.003). Conclusions HIV-associated TBM is devastating disease with a dismal prognosis. CSF findings included CSF neutrophil predominance, high rates of smear and culture positivity, and high rates of antituberculous drug resistance. Three baseline variables were independently associated with death: increased TBM grade; low serum sodium and decreased CSF lymphocyte percentage. PMID:18350135

Random Survival Forest in practice: a method for modelling complex metabolomics data in time to event analysis.

PubMed

Dietrich, Stefan; Floegel, Anna; Troll, Martina; Kühn, Tilman; Rathmann, Wolfgang; Peters, Anette; Sookthai, Disorn; von Bergen, Martin; Kaaks, Rudolf; Adamski, Jerzy; Prehn, Cornelia; Boeing, Heiner; Schulze, Matthias B; Illig, Thomas; Pischon, Tobias; Knüppel, Sven; Wang-Sattler, Rui; Drogan, Dagmar

2016-10-01

The application of metabolomics in prospective cohort studies is statistically challenging. Given the importance of appropriate statistical methods for selection of disease-associated metabolites in highly correlated complex data, we combined random survival forest (RSF) with an automated backward elimination procedure that addresses such issues. Our RSF approach was illustrated with data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, with concentrations of 127 serum metabolites as exposure variables and time to development of type 2 diabetes mellitus (T2D) as outcome variable. Out of this data set, Cox regression with a stepwise selection method was recently published. Replication of methodical comparison (RSF and Cox regression) was conducted in two independent cohorts. Finally, the R-code for implementing the metabolite selection procedure into the RSF-syntax is provided. The application of the RSF approach in EPIC-Potsdam resulted in the identification of 16 incident T2D-associated metabolites which slightly improved prediction of T2D when used in addition to traditional T2D risk factors and also when used together with classical biomarkers. The identified metabolites partly agreed with previous findings using Cox regression, though RSF selected a higher number of highly correlated metabolites. The RSF method appeared to be a promising approach for identification of disease-associated variables in complex data with time to event as outcome. The demonstrated RSF approach provides comparable findings as the generally used Cox regression, but also addresses the problem of multicollinearity and is suitable for high-dimensional data. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Beyond Trisomy 21: Phenotypic Variability in People with Down Syndrome Explained by Further Chromosome Mis-segregation and Mosaic Aneuploidy

PubMed Central

Potter, Huntington

2017-01-01

Phenotypic variability is a fundamental feature of the human population and is particularly evident among people with Down syndrome and/or Alzheimer’s disease. Herein, we review current theories of the potential origins of this phenotypic variability and propose a novel mechanism based on our finding that the Alzheimer’s disease-associated Aβ peptide, encoded on chromosome 21, disrupts the mitotic spindle, induces abnormal chromosome segregation, and produces mosaic populations of aneuploid cells in all tissues of people with Alzheimer’s disease and in mouse and cell models thereof. Thus, individuals exposed to increased levels of the Aβ peptide should accumulate mosaic populations of aneuploid cells, with different chromosomes affected in different tissues and in different individuals. Specifically, people with Down syndrome, who express elevated levels of Aβ peptide throughout their lifetimes, would be predicted to accumulate additional types of aneuploidy, beyond trisomy 21 and including changes in their trisomy 21 status, in mosaic cell populations. Such mosaic aneuploidy would introduce a novel form of genetic variability that could potentially underlie much of the observed phenotypic variability among people with Down syndrome, and possibly also among people with Alzheimer’s disease. This mosaic aneuploidy theory of phenotypic variability in Down syndrome is supported by several observations, makes several testable predictions, and identifies a potential approach to reducing the frequency of some of the most debilitating features of Down syndrome, including Alzheimer’s disease. PMID:29516054

Effects of Parkinson's Disease on Fundamental Frequency Variability in Running Speech.

PubMed

Bowen, Leah K; Hands, Gabrielle L; Pradhan, Sujata; Stepp, Cara E

2013-09-01

In Parkinson's Disease (PD), qualitative speech changes such as decreased variation in pitch and loudness are common, but quantitative vocal changes are not well documented. The variability of fundamental frequency (F0) in 32 individuals (23 male) with PD both ON and OFF levodopa medication was compared with 32 age-matched healthy controls (23 male). Participants read a single paragraph and estimates of fundamental frequency (F0) variability were determined for the entire reading passage as well as for the first and last sentences of the passage separately. F0 variability was significantly increased in controls relative to both PD groups and PD patients showed significantly higher F0 variability while ON medication relative to OFF. No significant effect of group was seen in the change in F0 variability from the beginning to the end of the reading passage. Female speakers were found to have higher F0 variability than males. F0 variability was both significantly reduced in PD relative to controls and significantly increased in patients with PD during use of dopaminergic medications. F0 variability changes over the course of reading a paragraph may not be indicative of PD but rather dependent on non-disease factors such as the linguistic characteristics of the text.

European hospital adherence to GOLD recommendations for chronic obstructive pulmonary disease (COPD) exacerbation admissions.

PubMed

Roberts, C Michael; Lopez-Campos, Jose Luis; Pozo-Rodriguez, Francisco; Hartl, Sylvia

2013-12-01

Understanding how European care of chronic obstructive pulmonary disease (COPD) admissions vary against guideline standards provides an opportunity to target appropriate quality improvement interventions. In 2010-2011 an audit of care against the 2010 'Global initiative for chronic Obstructive Lung Disease' (GOLD) standards was performed in 16 018 patients from 384 hospitals in 13 countries. Clinicians prospectively identified consecutive COPD admissions over a period of 8 weeks, recording clinical care measures on a web-based data tool. Data were analysed comparing adherence to 10 key management recommendations. Adherence varied between hospitals and across countries. The lack of available spirometry results and variable use of oxygen and non-invasive ventilation (NIV) are high impact areas identified for improvement.

Precision Medicine: The New Frontier in Idiopathic Pulmonary Fibrosis.

PubMed

Brownell, Robert; Kaminski, Naftali; Woodruff, Prescott G; Bradford, Williamson Z; Richeldi, Luca; Martinez, Fernando J; Collard, Harold R

2016-06-01

Precision medicine is defined by the National Institute of Health's Precision Medicine Initiative Working Group as an approach to disease treatment that takes into account individual variability in genes, environment, and lifestyle. There has been increased interest in applying the concept of precision medicine to idiopathic pulmonary fibrosis, in particular to search for genetic and molecular biomarker-based profiles (so called endotypes) that identify mechanistically distinct disease subgroups. The relevance of precision medicine to idiopathic pulmonary fibrosis is yet to be established, but we believe that it holds great promise to provide targeted and highly effective therapies to patients. In this manuscript, we describe the field's nascent efforts in genetic/molecular endotype identification and how environmental and behavioral subgroups may also be relevant to disease management.

A Personalized Approach to Managing Inflammatory Bowel Disease

PubMed Central

Kingsley, Michael J.

2016-01-01

The management of inflammatory bowel disease (IBD) requires a personalized approach to treat what is a heterogeneous group of patients with inherently variable disease courses. In its current state, personalized care of the IBD patient involves identifying patients at high risk for rapid progression to complications, selecting the most appropriate therapy for a given patient, using therapeutic drug monitoring, and achieving the individualized goal that is most appropriate for that patient. The growing body of research in this area allows clinicians to better predict outcomes for individual patients. Some paradigms, especially within the realm of therapeutic drug monitoring, have begun to change as therapy is targeted to individual patient results and goals. Future personalized medical decisions may allow specific therapeutic plans to draw on serologic, genetic, and microbial data for Crohn’s disease and ulcerative colitis patients. PMID:27499713

Attachment, childhood abuse, and IBD-related quality of life and disease activity outcomes.

PubMed

Caplan, Rachel A; Maunder, Robert G; Stempak, Joanne M; Silverberg, Mark S; Hart, Tae L

2014-05-01

This study examined attachment style as a moderator of the relationship between childhood abuse and inflammatory bowel disease (IBD)-related outcomes. Study participants were 205 patients with IBD from Mount Sinai Hospital in Toronto. Participants completed self-report questionnaires regarding personal relationships, abuse history, and IBD-related information. Multiple regression models were fit using 3 outcome variables: disease-related quality of life (QOL), disease activity for ulcerative colitis, and disease activity for Crohn's disease. Patients reporting less severe abuse and low levels of avoidant attachment had the highest levels of QOL, whereas patients reporting high levels of avoidant attachment had the lowest levels of QOL, regardless of abuse severity. Patients reporting greater anxious attachment had lower QOL scores. Patients reporting less severe abuse and low levels of avoidant attachment had the lowest levels of disease activity, whereas patients reporting high levels of avoidant attachment had the highest levels of ulcerative colitis-related disease activity, regardless of abuse severity. However, for anxious attachment, there was no significant main effect or significant interaction of abuse by anxious attachment on ulcerative colitis-related disease activity. Childhood abuse and attachment style were not found to be associated with Crohn's disease-related disease activity. Adult attachment style may moderate the relationship between childhood abuse and IBD-related outcomes, by impacting one's QOL and disease activity. Distinct types of insecure attachment styles may impact these relationships differently. Psychological interventions focusing on attachment styles of patients with IBD have the potential to improve IBD-related QOL and disease activity.

Plus Disease in Retinopathy of Prematurity: A Continuous Spectrum of Vascular Abnormality as a Basis of Diagnostic Variability.

PubMed

Campbell, J Peter; Kalpathy-Cramer, Jayashree; Erdogmus, Deniz; Tian, Peng; Kedarisetti, Dharanish; Moleta, Chace; Reynolds, James D; Hutcheson, Kelly; Shapiro, Michael J; Repka, Michael X; Ferrone, Philip; Drenser, Kimberly; Horowitz, Jason; Sonmez, Kemal; Swan, Ryan; Ostmo, Susan; Jonas, Karyn E; Chan, R V Paul; Chiang, Michael F

2016-11-01

To identify patterns of interexpert discrepancy in plus disease diagnosis in retinopathy of prematurity (ROP). We developed 2 datasets of clinical images as part of the Imaging and Informatics in ROP study and determined a consensus reference standard diagnosis (RSD) for each image based on 3 independent image graders and the clinical examination results. We recruited 8 expert ROP clinicians to classify these images and compared the distribution of classifications between experts and the RSD. Eight participating experts with more than 10 years of clinical ROP experience and more than 5 peer-reviewed ROP publications who analyzed images obtained during routine ROP screening in neonatal intensive care units. Expert classification of images of plus disease in ROP. Interexpert agreement (weighted κ statistic) and agreement and bias on ordinal classification between experts (analysis of variance [ANOVA]) and the RSD (percent agreement). There was variable interexpert agreement on diagnostic classifications between the 8 experts and the RSD (weighted κ, 0-0.75; mean, 0.30). The RSD agreement ranged from 80% to 94% for the dataset of 100 images and from 29% to 79% for the dataset of 34 images. However, when images were ranked in order of disease severity (by average expert classification), the pattern of expert classification revealed a consistent systematic bias for each expert consistent with unique cut points for the diagnosis of plus disease and preplus disease. The 2-way ANOVA model suggested a highly significant effect of both image and user on the average score (dataset A: P < 0.05 and adjusted R 2  = 0.82; and dataset B: P < 0.05 and adjusted R 2  = 0.6615). There is wide variability in the classification of plus disease by ROP experts, which occurs because experts have different cut points for the amounts of vascular abnormality required for presence of plus and preplus disease. This has important implications for research, teaching, and patient care for ROP and suggests that a continuous ROP plus disease severity score may reflect more accurately the behavior of expert ROP clinicians and may better standardize classification in the future. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Protein-driven inference of miRNA–disease associations

PubMed Central

Mørk, Søren; Pletscher-Frankild, Sune; Palleja Caro, Albert; Gorodkin, Jan; Jensen, Lars Juhl

2014-01-01

Motivation: MicroRNAs (miRNAs) are a highly abundant class of non-coding RNA genes involved in cellular regulation and thus also diseases. Despite miRNAs being important disease factors, miRNA–disease associations remain low in number and of variable reliability. Furthermore, existing databases and prediction methods do not explicitly facilitate forming hypotheses about the possible molecular causes of the association, thereby making the path to experimental follow-up longer. Results: Here we present miRPD in which miRNA–Protein–Disease associations are explicitly inferred. Besides linking miRNAs to diseases, it directly suggests the underlying proteins involved, which can be used to form hypotheses that can be experimentally tested. The inference of miRNAs and diseases is made by coupling known and predicted miRNA–protein associations with protein–disease associations text mined from the literature. We present scoring schemes that allow us to rank miRNA–disease associations inferred from both curated and predicted miRNA targets by reliability and thereby to create high- and medium-confidence sets of associations. Analyzing these, we find statistically significant enrichment for proteins involved in pathways related to cancer and type I diabetes mellitus, suggesting either a literature bias or a genuine biological trend. We show by example how the associations can be used to extract proteins for disease hypothesis. Availability and implementation: All datasets, software and a searchable Web site are available at http://mirpd.jensenlab.org. Contact: lars.juhl.jensen@cpr.ku.dk or gorodkin@rth.dk PMID:24273243

Celiac Disease: Diagnostic Standards and Dilemmas

PubMed Central

Kaswala, Dharmesh H.; Veeraraghavan, Gopal; Kelly, Ciaran P.; Leffler, Daniel A.

2015-01-01

Celiac Disease (CD) affects at least 1% of the population and evidence suggests that prevalence is increasing. The diagnosis of CD depends on providers being alert to both typical and atypical presentations and those situations in which patients are at high risk for the disease. Because of variable presentation, physicians need to have a low threshold for celiac testing. Robust knowledge of the pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools. Highly sensitive and specific serological assays including Endomysial Antibody (EMA), tissue transglutaminase (tTG), and Deamidated Gliadin Peptide (DGP) have greatly simplified testing for CD and serve as the foundation for celiac diagnosis. In addition, genetic testing for HLA DQ2 and DQ8 has become more widely available and there has been refinement of the gluten challenge for use in diagnostic algorithms. While diagnosis is usually straightforward, in special conditions including IgA deficiency, very young children, discrepant histology and serology, and adoption of a gluten free diet prior to testing, CD can be difficult to diagnose. In this review, we provide an overview of the history and current state of celiac disease diagnosis and provide guidance for evaluation of CD in difficult diagnostic circumstances. PMID:28943611

Rumination and behavioural factors in Parkinson's disease depression.

PubMed

Julien, Camille L; Rimes, Katharine A; Brown, Richard G

2016-03-01

Parkinson's disease is associated with high rates of depression. There is growing interest in non-pharmacological management including psychological approaches such as Cognitive Behaviour Therapy. To date, little research has investigated whether processes that underpin cognitive models of depression, on which such treatment is based, apply in patients with Parkinson's disease. The study aimed to investigate the contribution of core psychological factors to the presence and degree of depressive symptoms. 104 participants completed questionnaires measuring mood, motor disability and core psychological variables, including maladaptive assumptions, rumination, cognitive-behavioural avoidance, illness representations and cognitive-behavioural responses to symptoms. Regression analyses revealed that a small number of psychological factors accounted for the majority of depression variance, over and above that explained by overall disability. Participants reporting high levels of rumination, avoidance and symptom focusing experienced more severe depressive symptoms. In contrast, pervasive negative dysfunctional beliefs did not independently contribute to depression variance. Specific cognitive (rumination and symptom focusing) and behavioural (avoidance) processes may be key psychological markers of depression in Parkinson's disease and therefore offer important targets for tailored psychological interventions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

A Study on the Characteristics of Infrequent and Frequent Outpatients Visiting Korean Traditional Medical Facilities

PubMed Central

Yoon, Jinwon; Park, Haemo; Chu, Chaeshin; Choi, Sung-Yong; Lee, Kibum; Lee, Sundong

2015-01-01

Objectives This study was intended to analyze the characteristics of infrequent and frequent outpatients visiting Korean medical facilities, and find the related variables of frequent users. Methods The data source was the Report on the Usage and Consumption of Korean Medicine (2011) published by the Ministry of Health and Welfare and Korea Institute for Health and Social Affairs. We analyzed outpatient data using SAS 9.2. Results As much as 46.6% of the patients used Korean medical services over 11 times in 3 months. The proportion of frequent users increased depending on age, and their proportion was high in the low-income and low-education group. People with musculoskeletal disease, stroke, hypertension, and obesity were more likely to use Korean medical services. In general, patients were satisfied with their treatment, with frequent outpatients being more satisfied than infrequent outpatients. In logistic regression analysis, age and musculoskeletal disease were significant determinants of frequency of use of Korean medical services. Conclusion Age, musculoskeletal disease, and specific diseases were highly associated with frequent Korean medical utilization. PMID:26430614

Sphingomyelin in High-Density Lipoproteins: Structural Role and Biological Function

PubMed Central

Martínez-Beamonte, Roberto; Lou-Bonafonte, Jose M.; Martínez-Gracia, María V.; Osada, Jesús

2013-01-01

High-density lipoprotein (HDL) levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM) is the second most abundant phospholipid component and the major sphingolipid in HDL. Considering the marked presence of SM, the present review has focused on the current knowledge about this phospholipid by addressing its variable distribution among HDL lipoparticles, how they acquire this phospholipid, and the important role that SM plays in regulating their fluidity and cholesterol efflux from different cells. In addition, plasma enzymes involved in HDL metabolism such as lecithin–cholesterol acyltransferase or phospholipid transfer protein are inhibited by HDL SM content. Likewise, HDL SM levels are influenced by dietary maneuvers (source of protein or fat), drugs (statins or diuretics) and modified in diseases such as diabetes, renal failure or Niemann–Pick disease. Furthermore, increased levels of HDL SM have been shown to be an inverse risk factor for coronary heart disease. The complexity of SM species, described using new lipidomic methodologies, and their distribution in different HDL particles under many experimental conditions are promising avenues for further research in the future. PMID:23571495

Evaluation of acute pelvic pain in women.

PubMed

Kruszka, Paul S; Kruszka, Stephen J

2010-07-15

Diagnosis of pelvic pain in women can be challenging because many symptoms and signs are insensitive and nonspecific. As the first priority, urgent life-threatening conditions (e.g., ectopic pregnancy, appendicitis, ruptured ovarian cyst) and fertility-threatening conditions (e.g., pelvic inflammatory disease, ovarian torsion) must be considered. A careful history focusing on pain characteristics, review of systems, and gynecologic, sexual, and social history, in addition to physical examination helps narrow the differential diagnosis. The most common urgent causes of pelvic pain are pelvic inflammatory disease, ruptured ovarian cyst, and appendicitis; however, many other diagnoses in the differential may mimic these conditions, and imaging is often needed. Transvaginal ultrasonography should be the initial imaging test because of its sensitivities across most etiologies and its lack of radiation exposure. A high index of suspicion should be maintained for pelvic inflammatory disease when other etiologies are ruled out, because the presentation is variable and the prevalence is high. Multiple studies have shown that 20 to 50 percent of women presenting with pelvic pain have pelvic inflammatory disease. Adolescents and pregnant and postpartum women require unique considerations.

Unemployment among women with multiple sclerosis: the role of coping and perceived stress and support in the workplace.

PubMed

Strober, L B; Arnett, P A

2016-06-01

Unemployment is high among individuals with multiple sclerosis (MS). Certain disease variables and demographics have been found to distinguish employed and unemployed individuals. However, these variables only account for 14-20% of the variance. Other factors, such as coping, perceived stress and social support, in the workforce have been proposed, but not yet fully examined. The purpose of the present investigation was to examine the role of known factors associated with unemployment in MS, as well as coping and perceived work stress and social support. Sixty-eight women with MS were asked about their employment status and reasons for leaving. They completed a comprehensive assessment including measures of cognition, disease symptoms, psychological functioning, coping and stress. Consistent with previous findings, certain disease and demographic variables were associated with being unemployed. In particular, women who left work due to their MS were found to be older, had a longer disease duration and progressive course, reported greater disability and fatigue, and performed worse on a cognitive measure. However, we also found that coping style distinguished those who were employed from those who left work due to their MS. In particular, those who left work reported utilizing maladaptive coping mechanisms such as behavioral disengagement and substance use. With regard to perceived work stress and support, individuals who were employed reported that job security and fellow co-workers were more of an uplift than a hassle in their lives, suggesting some benefit in employment. These findings suggest that further consideration be given to role of coping and perception of the benefit of employment among individuals with MS when making recommendations regarding work decisions.

The risk of disabling, surgery and reoperation in Crohn's disease - A decision tree-based approach to prognosis.

PubMed

Dias, Cláudia Camila; Pereira Rodrigues, Pedro; Fernandes, Samuel; Portela, Francisco; Ministro, Paula; Martins, Diana; Sousa, Paula; Lago, Paula; Rosa, Isadora; Correia, Luis; Moura Santos, Paula; Magro, Fernando

2017-01-01

Crohn's disease (CD) is a chronic inflammatory bowel disease known to carry a high risk of disabling and many times requiring surgical interventions. This article describes a decision-tree based approach that defines the CD patients' risk or undergoing disabling events, surgical interventions and reoperations, based on clinical and demographic variables. This multicentric study involved 1547 CD patients retrospectively enrolled and divided into two cohorts: a derivation one (80%) and a validation one (20%). Decision trees were built upon applying the CHAIRT algorithm for the selection of variables. Three-level decision trees were built for the risk of disabling and reoperation, whereas the risk of surgery was described in a two-level one. A receiver operating characteristic (ROC) analysis was performed, and the area under the curves (AUC) Was higher than 70% for all outcomes. The defined risk cut-off values show usefulness for the assessed outcomes: risk levels above 75% for disabling had an odds test positivity of 4.06 [3.50-4.71], whereas risk levels below 34% and 19% excluded surgery and reoperation with an odds test negativity of 0.15 [0.09-0.25] and 0.50 [0.24-1.01], respectively. Overall, patients with B2 or B3 phenotype had a higher proportion of disabling disease and surgery, while patients with later introduction of pharmacological therapeutic (1 months after initial surgery) had a higher proportion of reoperation. The decision-tree based approach used in this study, with demographic and clinical variables, has shown to be a valid and useful approach to depict such risks of disabling, surgery and reoperation.

Implementation and utilization of genetic testing in personalized medicine

PubMed Central

Abul-Husn, Noura S; Owusu Obeng, Aniwaa; Sanderson, Saskia C; Gottesman, Omri; Scott, Stuart A

2014-01-01

Clinical genetic testing began over 30 years ago with the availability of mutation detection for sickle cell disease diagnosis. Since then, the field has dramatically transformed to include gene sequencing, high-throughput targeted genotyping, prenatal mutation detection, preimplantation genetic diagnosis, population-based carrier screening, and now genome-wide analyses using microarrays and next-generation sequencing. Despite these significant advances in molecular technologies and testing capabilities, clinical genetics laboratories historically have been centered on mutation detection for Mendelian disorders. However, the ongoing identification of deoxyribonucleic acid (DNA) sequence variants associated with common diseases prompted the availability of testing for personal disease risk estimation, and created commercial opportunities for direct-to-consumer genetic testing companies that assay these variants. This germline genetic risk, in conjunction with other clinical, family, and demographic variables, are the key components of the personalized medicine paradigm, which aims to apply personal genomic and other relevant data into a patient’s clinical assessment to more precisely guide medical management. However, genetic testing for disease risk estimation is an ongoing topic of debate, largely due to inconsistencies in the results, concerns over clinical validity and utility, and the variable mode of delivery when returning genetic results to patients in the absence of traditional counseling. A related class of genetic testing with analogous issues of clinical utility and acceptance is pharmacogenetic testing, which interrogates sequence variants implicated in interindividual drug response variability. Although clinical pharmacogenetic testing has not previously been widely adopted, advances in rapid turnaround time genetic testing technology and the recent implementation of preemptive genotyping programs at selected medical centers suggest that personalized medicine through pharmacogenetics is now a reality. This review aims to summarize the current state of implementing genetic testing for personalized medicine, with an emphasis on clinical pharmacogenetic testing. PMID:25206309

A Kernel Machine Method for Detecting Effects of Interaction Between Multidimensional Variable Sets: An Imaging Genetics Application

PubMed Central

Ge, Tian; Nichols, Thomas E.; Ghosh, Debashis; Mormino, Elizabeth C.

2015-01-01

Measurements derived from neuroimaging data can serve as markers of disease and/or healthy development, are largely heritable, and have been increasingly utilized as (intermediate) phenotypes in genetic association studies. To date, imaging genetic studies have mostly focused on discovering isolated genetic effects, typically ignoring potential interactions with non-genetic variables such as disease risk factors, environmental exposures, and epigenetic markers. However, identifying significant interaction effects is critical for revealing the true relationship between genetic and phenotypic variables, and shedding light on disease mechanisms. In this paper, we present a general kernel machine based method for detecting effects of interaction between multidimensional variable sets. This method can model the joint and epistatic effect of a collection of single nucleotide polymorphisms (SNPs), accommodate multiple factors that potentially moderate genetic influences, and test for nonlinear interactions between sets of variables in a flexible framework. As a demonstration of application, we applied the method to data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to detect the effects of the interactions between candidate Alzheimer's disease (AD) risk genes and a collection of cardiovascular disease (CVD) risk factors, on hippocampal volume measurements derived from structural brain magnetic resonance imaging (MRI) scans. Our method identified that two genes, CR1 and EPHA1, demonstrate significant interactions with CVD risk factors on hippocampal volume, suggesting that CR1 and EPHA1 may play a role in influencing AD-related neurodegeneration in the presence of CVD risks. PMID:25600633

Associates of School Absenteeism in Adolescents With Sickle Cell Disease

PubMed Central

Schwartz, Lisa A.; Radcliffe, Jerilynn; Barakat, Lamia P.

2009-01-01

Background Despite high rates of school absenteeism in adolescents with sickle cell disease (SCD), the issue remains understudied. Potential associates of school absenteeism in adolescents with SCD include demographic (age, income), psychosocial (IQ, self-efficacy, competence, internalizing symptoms, negative thinking), and health-related (hemoglobin, health-care utilization, pain, disease knowledge). Procedure Forty participants ages 12–18 completed measures of psychosocial functioning, IQ, and pain. Medical chart reviews identified other health-related variables. A subsample also completed an assessment of goals. Using school records, absenteeism was the percent of school days missed in the previous year. Correlations tested associates of absenteeism and linear regression tested a model of absenteeism. Results Participants missed an average of 12% of the school year and more than 35% missed at least 1 month of school. Health-related and psychosocial variables, but not demographic variables, correlated with absenteeism. Attendance at clinic appointments and parent-reported teen pain frequency were significant associates of absenteeism in the regression model. For those who completed goal assessment, over 40% of goals identified were academically focused. Absenteeism was positively related to current academic goals and health-related hindrance of academic goals, and negatively related to future-oriented academic goals. Conclusions School absenteeism is a significant problem for adolescents with SCD despite the presence of academic goals. Collaboration between schools, parents, patients, and providers to understand and manage the impact of SCD on school attendance is recommended. PMID:19006248

What drives attitude towards telemedicine among families of pediatric patients? A survey.

PubMed

Russo, Luisa; Campagna, Ilaria; Ferretti, Beatrice; Agricola, Eleonora; Pandolfi, Elisabetta; Carloni, Emanuela; D'Ambrosio, Angelo; Gesualdo, Francesco; Tozzi, Alberto E

2017-01-17

Telemedicine has been recognized as a way to improve accessibility, quality, and efficiency of care. In view of the introduction of new telemedicine services, we conducted a survey through a self-administered questionnaire among families of children attending the Bambino Gesù Children's Hospital IRCCS, a tertiary care children's hospital located in Rome, Italy. We investigated sociodemographic data, clinical information, technological profile, attitude towards telemedicine, perceived advantages of telemedicine, fears regarding telemedicine, willingness to use a smartphone app providing telemedicine services and willingness to use a televisit service. Through logistic regression, we explored the effect of sociodemographic and clinical variables and technological profile on willingness of using a telemedicine app and a televisit service. We enrolled a total of 751 families. Most patients had a high technological profile, 81% had at least one account on a social network. Whatsapp was the most popular messaging service (76%). Seventy-two percent of patients would use an app for telemedicine services and 65% would perform a televisit. Owning a tablet was associated with both outcome variables - respectively: OR 2.216, 95% CI 1.358-3.616 (app) and OR 2.117, 95% CI 1.415-3.168 (televisit). Kind of hospitalization, diagnosis of a chronic disease, disease severity and distance from the health care center were not associated with the outcome variables. Families of pediatric patients with different clinical problems are keen to embark in telemedicine programs, independently from severity of disease or chronicity, and of distance from the hospital.

Climate and environmental change drives Ixodes ricinus geographical expansion at the northern range margin.

PubMed

Jore, Solveig; Vanwambeke, Sophie O; Viljugrein, Hildegunn; Isaksen, Ketil; Kristoffersen, Anja B; Woldehiwet, Zerai; Johansen, Bernt; Brun, Edgar; Brun-Hansen, Hege; Westermann, Sebastian; Larsen, Inger-Lise; Ytrehus, Bjørnar; Hofshagen, Merete

2014-01-08

Global environmental change is causing spatial and temporal shifts in the distribution of species and the associated diseases of humans, domesticated animals and wildlife. In the on-going debate on the influence of climate change on vectors and vector-borne diseases, there is a lack of a comprehensive interdisciplinary multi-factorial approach utilizing high quality spatial and temporal data. We explored biotic and abiotic factors associated with the latitudinal and altitudinal shifts in the distribution of Ixodes ricinus observed during the last three decades in Norway using antibodies against Anaplasma phagocytophilum in sheep as indicators for tick presence. Samples obtained from 2963 sheep from 90 farms in 3 ecologically different districts during 1978 - 2008 were analysed. We modelled the presence of antibodies against A. phagocytophilum to climatic-, environmental and demographic variables, and abundance of wild cervids and domestic animals, using mixed effect logistic regressions. Significant predictors were large diurnal fluctuations in ground surface temperature, spring precipitation, duration of snow cover, abundance of red deer and farm animals and bush encroachment/ecotones. The length of the growth season, mean temperature and the abundance of roe deer were not significant in the model. Our results highlight the need to consider climatic variables year-round to disentangle important seasonal variation, climatic threshold changes, climate variability and to consider the broader environmental change, including abiotic and biotic factors. The results offer novel insight in how tick and tick-borne disease distribution might be modified by future climate and environmental change.

Pathogenesis of Arrhythmogenic Cardiomyopathy

PubMed Central

Asimaki, Angeliki; Kleber, Andre G.; Saffitz, Jeffrey E.

2015-01-01

Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease. It is characterized by frequent ventricular arrhythmias and increased risk of sudden cardiac death typically arising as an early manifestation before the onset of significant myocardial remodeling. Myocardial degeneration, often confined to the right ventricular free wall, with replacement by fibrofatty scar tissue, develops in many patients. ACM is a familial disease but genetic penetrance can be low and disease expression is highly variable. Inflammation may promote disease progression. It also appears that exercise increases disease penetrance and accelerates its development. More than 60% of probands harbor mutations in genes encoding desmosomal proteins, which has raised the possibility that defective cell-cell adhesion may play a role in disease pathogenesis. Recent advances have implicated changes in the canonical Wnt/β-catenin and Hippo signaling pathways and defects in forwarding trafficking of ion channels and other proteins to the intercalated disk in cardiac myocytes. This review summarizes current understanding of the pathogenesis of ACM and highlights future research directions. PMID:26199027

Toward precision medicine in Alzheimer's disease.

PubMed

Reitz, Christiane

2016-03-01

In Western societies, Alzheimer's disease (AD) is the most common form of dementia and the sixth leading cause of death. In recent years, the concept of precision medicine, an approach for disease prevention and treatment that is personalized to an individual's specific pattern of genetic variability, environment and lifestyle factors, has emerged. While for some diseases, in particular select cancers and a few monogenetic disorders such as cystic fibrosis, significant advances in precision medicine have been made over the past years, for most other diseases precision medicine is only in its beginning. To advance the application of precision medicine to a wider spectrum of disorders, governments around the world are starting to launch Precision Medicine Initiatives, major efforts to generate the extensive scientific knowledge needed to integrate the model of precision medicine into every day clinical practice. In this article we summarize the state of precision medicine in AD, review major obstacles in its development, and discuss its benefits in this highly prevalent, clinically and pathologically complex disease.

Between a bug and a hard place: Trypanosoma cruzi genetic diversity and the clinical outcomes of Chagas disease

PubMed Central

Messenger, Louisa A; Miles, Michael A; Bern, Caryn

2015-01-01

Over the last 30 years, concomitant with successful transnational disease control programs across Latin America, Chagas disease has expanded from a neglected, endemic parasitic infection of the rural poor to an urbanized chronic disease, and now a potentially emergent global health problem. Trypanosoma cruzi infection has a highly variable clinical course, ranging from complete absence of symptoms to severe and often fatal cardiovascular and/or gastrointestinal manifestations. To date, few correlates of clinical disease progression have been identified. Elucidating a putative role for T. cruzi strain diversity in Chagas disease pathogenesis is complicated by the scarcity of parasites in clinical specimens and the limitations of our contemporary genotyping techniques. This article systematically reviews the historical literature, given our current understanding of parasite genetic diversity, to evaluate the evidence for any association between T. cruzi genotype and chronic clinical outcome, risk of congenital transmission or reactivation and orally transmitted outbreaks. PMID:26162928

Identifying environmental, social, and psychological correlates of meeting the recommended physical activity levels for colon cancer prevention among Japanese adults.

PubMed

Ishii, Kaori; Shibata, Ai; Oka, Koichiro

2013-11-01

Although physical activity reduces the risk of diseases such as cancer, diabetes and cardiovascular disease, a large proportion of the population is not sufficiently physically active. Therefore, the present study examined the environmental, social, and psychological correlates for meeting the 2 recommended physical activity criteria: ≥420 min per week of at least moderate-intensity activity (MPA criterion) and ≥210 min per week of vigorous activity (VPA criterion) for colon cancer prevention among Japanese adults. Cross-sectional study. The sample included 2000 Japanese adults aged 20-79 years. An Internet-based survey was used to assess seven sociodemographic variables (e.g., education level, employment status), environmental variables (home fitness equipment, access to facilities, neighborhood safety, aesthetic sensibilities, and frequency of observing others exercising, residential area), social variables (social support), psychological variables (self-efficacy, perceived positive (pros) and negative (cons) aspects of exercise), and physical activity. The adjusted odds of meeting each physical activity criterion by these variables were calculated. Overall, 22.3% of the study population met the criterion of MPA, and 7.3% met the criterion of VPA. Having high self-efficacy, fewer perceived cons, possessing home fitness equipment, reporting enjoyable scenery, and living in a rural area were significantly associated with meeting the recommended criteria. Participants who met the 2 activity recommendations differed by self-efficacy, cons, possession of home fitness equipment, reporting of enjoyable scenery, and residential area. These findings imply that strategies to promote more intense physical activities specifically in terms of these variables may be necessary for colon cancer prevention. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Electronic medical record integration with a database for adult congenital heart disease: Early experience and progress in automating multicenter data collection.

PubMed

Broberg, Craig S; Mitchell, Julie; Rehel, Silven; Grant, Andrew; Gianola, Ann; Beninato, Peter; Winter, Christiane; Verstappen, Amy; Valente, Anne Marie; Weiss, Joseph; Zaidi, Ali; Earing, Michael G; Cook, Stephen; Daniels, Curt; Webb, Gary; Khairy, Paul; Marelli, Ariane; Gurvitz, Michelle Z; Sahn, David J

2015-10-01

The adoption of electronic health records (EHR) has created an opportunity for multicenter data collection, yet the feasibility and reliability of this methodology is unknown. The aim of this study was to integrate EHR data into a homogeneous central repository specifically addressing the field of adult congenital heart disease (ACHD). Target data variables were proposed and prioritized by consensus of investigators at five target ACHD programs. Database analysts determined which variables were available within their institutions' EHR and stratified their accessibility, and results were compared between centers. Data for patients seen in a single calendar year were extracted to a uniform database and subsequently consolidated. From 415 proposed target variables, only 28 were available in discrete formats at all centers. For variables of highest priority, 16/28 (57%) were available at all four sites, but only 11% for those of high priority. Integration was neither simple nor straightforward. Coding schemes in use for congenital heart diagnoses varied and would require additional user input for accurate mapping. There was considerable variability in procedure reporting formats and medication schemes, often with center-specific modifications. Despite the challenges, the final acquisition included limited data on 2161 patients, and allowed for population analysis of race/ethnicity, defect complexity, and body morphometrics. Large-scale multicenter automated data acquisition from EHRs is feasible yet challenging. Obstacles stem from variability in data formats, coding schemes, and adoption of non-standard lists within each EHR. The success of large-scale multicenter ACHD research will require institution-specific data integration efforts. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Modelling approaches: the case of schizophrenia.

PubMed

Heeg, Bart M S; Damen, Joep; Buskens, Erik; Caleo, Sue; de Charro, Frank; van Hout, Ben A

2008-01-01

Schizophrenia is a chronic disease characterized by periods of relative stability interrupted by acute episodes (or relapses). The course of the disease may vary considerably between patients. Patient histories show considerable inter- and even intra-individual variability. We provide a critical assessment of the advantages and disadvantages of three modelling techniques that have been used in schizophrenia: decision trees, (cohort and micro-simulation) Markov models and discrete event simulation models. These modelling techniques are compared in terms of building time, data requirements, medico-scientific experience, simulation time, clinical representation, and their ability to deal with patient heterogeneity, the timing of events, prior events, patient interaction, interaction between co-variates and variability (first-order uncertainty). We note that, depending on the research question, the optimal modelling approach should be selected based on the expected differences between the comparators, the number of co-variates, the number of patient subgroups, the interactions between co-variates, and simulation time. Finally, it is argued that in case micro-simulation is required for the cost-effectiveness analysis of schizophrenia treatments, a discrete event simulation model is best suited to accurately capture all of the relevant interdependencies in this chronic, highly heterogeneous disease with limited long-term follow-up data.

The wild tomato species Solanum chilense shows variation in pathogen resistance between geographically distinct populations

PubMed Central

Scheikl, Daniela; Tellier, Aurélien

2017-01-01

Wild tomatoes are a valuable source of disease resistance germplasm for tomato (Solanum lycopersicum) breeders. Many species are known to possess a certain degree of resistance against certain pathogens; however, evolution of resistance traits is yet poorly understood. For some species, like Solanum chilense, both differences in habitat and within species genetic diversity are very large. Here we aim to investigate the occurrence of spatially heterogeneous coevolutionary pressures between populations of S. chilense. We investigate the phenotypic differences in disease resistance within S. chilense against three common tomato pathogens (Alternaria solani, Phytophthora infestans and a Fusarium sp.) and confirm high degrees of variability in resistance properties between selected populations. Using generalised linear mixed models, we show that disease resistance does not follow the known demographic patterns of the species. Models with up to five available climatic and geographic variables are required to best describe resistance differences, confirming the complexity of factors involved in local resistance variation. We confirm that within S. chilense, resistance properties against various pathogens show a mosaic pattern and do not follow environmental patterns, indicating the strength of local pathogen pressures. Our study can form the basis for further investigations of the genetic traits involved. PMID:28133579

The wild tomato species Solanum chilense shows variation in pathogen resistance between geographically distinct populations.

PubMed

Stam, Remco; Scheikl, Daniela; Tellier, Aurélien

2017-01-01

Wild tomatoes are a valuable source of disease resistance germplasm for tomato ( Solanum lycopersicum ) breeders. Many species are known to possess a certain degree of resistance against certain pathogens; however, evolution of resistance traits is yet poorly understood. For some species, like Solanum chilense , both differences in habitat and within species genetic diversity are very large. Here we aim to investigate the occurrence of spatially heterogeneous coevolutionary pressures between populations of S. chilense . We investigate the phenotypic differences in disease resistance within S. chilense against three common tomato pathogens ( Alternaria solani , Phytophthora infestans and a Fusarium sp .) and confirm high degrees of variability in resistance properties between selected populations. Using generalised linear mixed models, we show that disease resistance does not follow the known demographic patterns of the species. Models with up to five available climatic and geographic variables are required to best describe resistance differences, confirming the complexity of factors involved in local resistance variation. We confirm that within S. chilense , resistance properties against various pathogens show a mosaic pattern and do not follow environmental patterns, indicating the strength of local pathogen pressures. Our study can form the basis for further investigations of the genetic traits involved.

[A primer on Wilson disease for the general practitioner].

PubMed

Hiroz, Philippe; Antonino, Anca; Doerig, Christopher; Pache, Isabelle; Moradpour, Darius

2011-09-07

Wilson disease (WD) is an inherited disorder of hepatic copper excretion leading to toxic accumulation of copper in the liver as well as the brain, cornea, and other organs. The defect is due to mutations of the copper-transporting ATPase ATP7B. Clinical manifestations are highly variable and comprise acute liver failure, chronic hepatitis and cirrhosis as well as neurological or psychiatric symptoms. The Kayser-Fleischer corneal ring is pathognomonic but absent in about 50% of patients with hepatic manifestations alone. A high index of suspicion in clinically compatible situations is key, with a combination of laboratory tests allowing the diagnosis of WD. Treatment is based on the use of chelating agents, D-penicillamine or trientine. Liver transplantation should be considered for patients with acute liver failure or advanced cirrhosis.

Macro- and microperfusion during application of a new compression system, designed for patients with leg ulcer and concomitant peripheral arterial occlusive disease.

PubMed

Jünger, Michael; Haase, Hermann; Schwenke, Linda; Bichel, Jens; Schuren, Jan; Ladwig, Andrea

2013-01-01

To investigate macro- and microperfusion during 14 days of treatment with a new 2-layer compression system (3M™ Coban™ 2 Lite), designed for patients with leg ulcer and concomitant peripheral arterial occlusive disease. A single-centre, open-label, prospective pilot study was performed with 15 subjects suffering from peripheral arterial occlusive disease with an ankle brachial pressure index (ABPI) of 0.5-0.8, who volunteered to have their 'study leg' bandaged with the new system. Coincident leg ulcer or chronic venous disease was not mandatory. All subjects received the new compression system, which stayed in place from 1 up to 4 days according to scheduled study visits. The system was reapplied by study personnel at each clinical visit (days 1, 2, 3, 4, 7, 10 and 14). The study participation stopped after 14 days. At each clinical visit safety assessments were performed: measurement of acral pulsation to capture macroperfusion; laser Doppler fluxmetry to capture microperfusion; clinical signs of pressure related skin damage, hypoxia-related pain and sub-bandage pressure measurement. In addition, the leg volume was measured and a comfort questionnaire was completed. An average sub-bandage pressure in standing position of approximately 30 mmHg was measured at the B1 location immediately after bandage application. Laser Doppler fluxmetry demonstrated positive effects on microcirculation regarding vasomotion and respiratory reflux. No change of the cardiac signal appeared. For acrale pulsations a high intraindividual variability was found with no clear interference to the bandage application. No pressure-related skin damage or hypoxia-related pain was detected. After application of the new compression system in subjects with moderate PAOD, laser Doppler fluxmetry indicated significant improvements of the microcirculation. High variability and lack of correlation to clinical symptoms was found for the acral pulsation. The new compression system revealed a high grade of tolerability and a good safety profile.

Effect of e-health on medical expenditures of outpatients with lifestyle-related diseases.

PubMed

Minetaki, Kazunori; Akematsu, Yuji; Tsuji, Masatsugu

2011-10-01

We analyzed the effect of e-health on medical expenditures in Nishi-aizu Town, Fukushima Prefecture, Japan, using panel data of medical expenditures for about 400 residents from 2002 to 2006. The Nishi-aizu Town system was introduced in 1994 and is still successfully operating as one of the longest running implementations of e-health in Japan. The town office maintains a register of receipts for medical expenditures paid by the National Health Insurance system and provides data on e-health users, allowing users and nonusers of e-health and their respective costs to be distinguished. Here, we focus on patients with lifestyle-related diseases such as high blood pressure, diabetes, stroke, heart failure, etc. This article postulates that e-health reduces medical expenditures via two mechanisms, decreasing travel expenses and preventing symptoms from worsening. The former implies that e-health monitoring allows patients at home to visit medical institutions less frequently, and the latter that the symptoms experienced by e-health users are less severe than those experienced by nonusers. We termed these the travel cost effect and opportunity cost effect, respectively. Chronic conditions tend not to occur singly, and many patients have more than one; for example, patients with high blood pressure or diabetes also likely have heart disease at the same time. This multiplicity of conditions hampers cost analysis. Among methodological issues, a number of recent empirical health analyses have focused on the endogenous problem of explanatory variables. Here, we solved this problem using the generalized method moments (GMM) system, which allows treatment of not only the endogenous problem of explanatory variables but also the dynamic relationship among variables, which arise due to the chronic time-lagged effect of lifestyle-related diseases on patients. We also examined a second important methodological problem related to reverse correlation between the medical expenditures of an outpatient and e-health and took sampling biases into consideration. We concluded that this control of endogeneity through system GMM confirms that the relationship between the medical expenditures of an outpatient and e-health shows causation rather than simple correlation and that e-health use, duration of e-health use, and frequency of e-health use can reduce outpatient medical expenditures for lifestyle-related diseases.

China's Air Quality and Respiratory Disease Mortality Based on the Spatial Panel Model.

PubMed

Cao, Qilong; Liang, Ying; Niu, Xueting

2017-09-18

Background : Air pollution has become an important factor restricting China's economic development and has subsequently brought a series of social problems, including the impact of air pollution on the health of residents, which is a topical issue in China. Methods : Taking into account this spatial imbalance, the paper is based on the spatial panel data model PM 2.5 . Respiratory disease mortality in 31 Chinese provinces from 2004 to 2008 is taken as the main variable to study the spatial effect and impact of air quality and respiratory disease mortality on a large scale. Results : It was found that there is a spatial correlation between the mortality of respiratory diseases in Chinese provinces. The spatial correlation can be explained by the spatial effect of PM 2.5 pollutions in the control of other variables. Conclusions : Compared with the traditional non-spatial model, the spatial model is better for describing the spatial relationship between variables, ensuring the conclusions are scientific and can measure the spatial effect between variables.

American Thoracic Society/National Heart, Lung, and Blood Institute Asthma-Chronic Obstructive Pulmonary Disease Overlap Workshop Report.

PubMed

Woodruff, Prescott G; van den Berge, Maarten; Boucher, Richard C; Brightling, Christopher; Burchard, Esteban G; Christenson, Stephanie A; Han, MeiLan K; Holtzman, Michael J; Kraft, Monica; Lynch, David A; Martinez, Fernando D; Reddel, Helen K; Sin, Don D; Washko, George R; Wenzel, Sally E; Punturieri, Antonello; Freemer, Michelle M; Wise, Robert A

2017-08-01

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic obstructive lung diseases with an associated high burden of disease. Asthma, which is often allergic in origin, frequently begins in infancy or childhood with variable airflow obstruction and intermittent wheezing, cough, and dyspnea. Patients with COPD, in contrast, are usually current or former smokers who present after the age of 40 years with symptoms (often persistent) including dyspnea and a productive cough. On the basis of age and smoking history, it is often easy to distinguish between asthma and COPD. However, some patients have features compatible with both diseases. Because clinical studies typically exclude these patients, their underlying disease mechanisms and appropriate treatment remain largely uncertain. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the American Thoracic Society, convened a workshop of investigators in San Francisco, California on May 14, 2016. At the workshop, current understanding of asthma-COPD overlap was discussed among clinicians, pathologists, radiologists, epidemiologists, and investigators with expertise in asthma and COPD. They considered knowledge gaps in our understanding of asthma-COPD overlap and identified strategies and research priorities that will advance its understanding. This report summarizes those discussions.

Climate variability, weather and enteric disease incidence in New Zealand: time series analysis.

PubMed

Lal, Aparna; Ikeda, Takayoshi; French, Nigel; Baker, Michael G; Hales, Simon

2013-01-01

Evaluating the influence of climate variability on enteric disease incidence may improve our ability to predict how climate change may affect these diseases. To examine the associations between regional climate variability and enteric disease incidence in New Zealand. Associations between monthly climate and enteric diseases (campylobacteriosis, salmonellosis, cryptosporidiosis, giardiasis) were investigated using Seasonal Auto Regressive Integrated Moving Average (SARIMA) models. No climatic factors were significantly associated with campylobacteriosis and giardiasis, with similar predictive power for univariate and multivariate models. Cryptosporidiosis was positively associated with average temperature of the previous month (β =  0.130, SE =  0.060, p <0.01) and inversely related to the Southern Oscillation Index (SOI) two months previously (β =  -0.008, SE =  0.004, p <0.05). By contrast, salmonellosis was positively associated with temperature (β  = 0.110, SE = 0.020, p<0.001) of the current month and SOI of the current (β  = 0.005, SE = 0.002, p<0.050) and previous month (β  = 0.005, SE = 0.002, p<0.05). Forecasting accuracy of the multivariate models for cryptosporidiosis and salmonellosis were significantly higher. Although spatial heterogeneity in the observed patterns could not be assessed, these results suggest that temporally lagged relationships between climate variables and national communicable disease incidence data can contribute to disease prediction models and early warning systems.

High self-efficacy predicts adherence to surveillance colonoscopy in inflammatory bowel disease.

PubMed

Friedman, Sonia; Cheifetz, Adam S; Farraye, Francis A; Banks, Peter A; Makrauer, Frederick L; Burakoff, Robert; Farmer, Barbara; Torgersen, Leanne N; Wahl, Kelly E

2014-09-01

Patients with extensive ulcerative colitis or Crohn's disease of the colon have an increased risk of colon cancer and require colonoscopic surveillance. In this study, we assessed individual self-efficacy (SE) to estimate the probability of adherence to surveillance colonoscopies. Three hundred seventy-eight patients with ulcerative colitis or Crohn's disease of the colon for at least 7 years and with at least one third of the colon involved participated in this cross-sectional questionnaire study performed at 3 tertiary referral inflammatory bowel disease clinics. Medical charts were abstracted for demographic and clinical variables. The questionnaire contained a group of items assessing SE for undergoing colonoscopy. We validated our 20-question SE scale and used 8 of the items that highlighted scheduling, preparation, and postprocedure recovery, to develop 2 shorter SE scales. All 3 scales were reliable with Cronbach's α ranging from 0.845 to 0.905 and correlated with chart-documented adherence to surveillance colonoscopy (P < 0.001). We then developed logistic regression models to predict adherence to surveillance colonoscopy using each scale separately along with other key variables (i.e., disease location, knowledge of correct adherence intervals, and information sources of patients consulted regarding Crohn's disease and ulcerative colitis) and demonstrated model accuracy up to 74%. SE, as measured by our validated scales, correlates with chart-adherence to surveillance colonoscopy. Our adherence model, which includes SE, predicts adherence with 74% certainty. An 8-item validated clinical questionnaire can be administered to assess whether patients in this population may require further intervention for adherence.

Impact of rare diseases in oral health

PubMed Central

Molina-García, Ana; Castellanos-Cosano, Lizett; Posada-de la Paz, Manuel

2016-01-01

Background Rare diseases (RD) are those that present a lower prevalence than 5 cases per 10.000 population. The main objective of this review was to study the effect on oral health in rare diseases, while the secondary objective of the study is theme upgrade. Material and Methods Comparative observational case-control studies were analysed and a systematic review was conducted in PubMed. Each rare disease listed on the statistical data record of the Health Portal of the Ministry of Equality, Health and Social Policies Board of Andalusia was associated with “oral health”. The variables studied included dental, oral mucosa and occlusion alterations, oral pathologies (caries, periodontal disease) and other alterations (mouth breathing, parafunctional habits, etc). A bias analysis of the variable caries was conducted. Results Six RD were selected through our inclusion and exclusion criteria (hypogammaglobulinemia, Rett syndrome, Marfan syndrome, Prader-Willi syndrome, cystic fibrosis and Cri du chat syndrome) in a total of 8 publications, of which four trials were classified as high risk of bias and one of them as medium risk. There were not trials with low risk of bias. Conclusions The main statistically significant differences found by Syndrome compared to a control group were in Hypogammaglobulinemia with a greater tendency to enamel hypoplasia and dry mouth. The Rett syndrome had, as well, a greater tendency to an anterior open bite, ogival palate, bruxism, mouth breathing and tongue thrusting. Prader-Willi syndrome had a tendency of dental erosion, and Cri du chat syndrome showed a higher association to Tannerella forsythia. Key words:Rare diseases, oral health. PMID:27475682

Recent advances in understanding idiopathic pulmonary fibrosis

PubMed Central

Daccord, Cécile; Maher, Toby M.

2016-01-01

Despite major research efforts leading to the recent approval of pirfenidone and nintedanib, the dismal prognosis of idiopathic pulmonary fibrosis (IPF) remains unchanged. The elaboration of international diagnostic criteria and disease stratification models based on clinical, physiological, radiological, and histopathological features has improved the accuracy of IPF diagnosis and prediction of mortality risk. Nevertheless, given the marked heterogeneity in clinical phenotype and the considerable overlap of IPF with other fibrotic interstitial lung diseases (ILDs), about 10% of cases of pulmonary fibrosis remain unclassifiable. Moreover, currently available tools fail to detect early IPF, predict the highly variable course of the disease, and assess response to antifibrotic drugs. Recent advances in understanding the multiple interrelated pathogenic pathways underlying IPF have identified various molecular phenotypes resulting from complex interactions among genetic, epigenetic, transcriptional, post-transcriptional, metabolic, and environmental factors. These different disease endotypes appear to confer variable susceptibility to the condition, differing risks of rapid progression, and, possibly, altered responses to therapy. The development and validation of diagnostic and prognostic biomarkers are necessary to enable a more precise and earlier diagnosis of IPF and to improve prediction of future disease behaviour. The availability of approved antifibrotic therapies together with potential new drugs currently under evaluation also highlights the need for biomarkers able to predict and assess treatment responsiveness, thereby allowing individualised treatment based on risk of progression and drug response. This approach of disease stratification and personalised medicine is already used in the routine management of many cancers and provides a potential road map for guiding clinical care in IPF. PMID:27303645

Relationship between overweight-obesity and periodontal disease in Mexico.

PubMed

Zermeño-Ibarra, Jorge A; Delgado-Pastrana, Soledad; Patiño-Marín, Nuria; Loyola-Rodríguez, Juan P

2010-01-01

The aim of this study was to examine the association between overweight-obesity and periodontal disease in subjects who attended the clinic of Periodontics, Faculty of Dentistry, San Luis de Potosi, México. This was cross-sectional study involving 88 subjects--60 without overweight-obesity and 28 with overweight-obesity. The following clinical parameters were evaluated: dental bacterial plaque, index of calculus, gingivitis, probing depth and periodontal disease index (PDI). When comparing the group of subjects with overweight-obesity to the control, there were statistically significant differences in the variables calculus (p = 0.0015), gingivitis (p = 0.0050) and periodontal disease (p = 0.0154). Regarding the logistic regression analysis, the dependent variable was subjects with and without overweight-obesity and the independent variables were sex, age and periodontal disease. We found statistically significant differences (p = 0.0162) with OR = 3.16 in periodontal disease. Periodontal disease showed statistically significant differences in the group of subjects with overweight-obesity. The oral health of subjects with overweight-obesity should be supervised and checked in order to prevent oral alterations.

Recent Advancements in Diagnosis and Therapy of Liver Cirrhosis.

PubMed

Romanelli, Roberto Giulio; Stasi, Cristina

2016-01-01

Cirrhosis is a diffuse pathophysiological state of the liver considered to be the final stage of various liver injuries, characterized by chronic necroinflammatory and fibrogenetic processes, with subsequent conversion of normal liver architecture into structurally abnormal nodules, dense fibrotic septa, concomitant parenchymal exaustment and collapse of the liver tissue. Alcoholic liver disease and chronic infections due to HBV and/or HCV constitute the main causes of liver cirrhosis worldwide. During a lag time of 15 to 30 years, chronic liver diseases can lead to liver cirrhosis and its complications. Active hepatic inflammation plays a pivotal role in the inflammation- necrosis-regeneration process, which eventually leads to liver cirrhosis and hepatocellular carcinoma. Prognosis of liver cirrhosis is highly variable and influenced by several variables, such as etiology, severity of liver disease, presence of complications and comorbidities. In advanced cirrhosis, survival decreases to one or two years. Correct advanced diagnosis and selected treatment with different molecules may help in understanding mechanisms of fibrogenesis, the driving forces of cirrhosis's pathogenesis, and the scrupulous approach to more effective therapeutic procedures. Prevention of fibrosis with further deterioration of liver function through specific treatments is always required, through the removal of the underlying causes of liver disease. Advanced liver disease, with subsequent complications, requires targeted treatment. Therefore, the aim of this review is to assess the diagnosis and treatment of liver cirrhosis on the pathophysiological bases, searching for relevant studies published in English using the PubMed database from 2011 to the present.

Genetic mutations in Gorlin-Goltz syndrome

PubMed Central

Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

2013-01-01

Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management. PMID:24339558

Genetic mutations in Gorlin-Goltz syndrome.

PubMed

Daneswari, Muthumula; Reddy, Mutjumula Swamy Ranga

2013-07-01

Gorlin-Goltz syndrome is a rare multisystemic disease inherited in a dominant autosomal at a high level of penetrance and variable expressiveness. It is mainly characterized by basal cell carcinoma, odontogenic keratocyst and skeletal anomalies. Diagnosis is based upon established major and minor clinical and radiographic criteria and gene mutation analysis. This article presents a case of Gorlin-Goltz syndrome, its genetic predisposition, diagnosis and management.

Pl17 is a novel gene independent of known downy mildew resistance genes in the cultivated sunflower (Helianthus annuus L.)

USDA-ARS?s Scientific Manuscript database

Downy mildew (DM), caused by Plasmopara halstedii (Farl.) Berl. et de Toni, is one of the serious sunflower diseases in the world due to its high virulence and the variability of the pathogen. DM resistance in the USDA inbred line, HA 458, has been shown to be effective against all virulent races of...

A Physiologic-Based Approach to the Treatment of Acute Hyperkalemia

PubMed Central

Shingarev, Roman; Allon, Michael

2014-01-01

Hyperkalemia is a common and potentially lethal disorder. Given its variable presentation clinicians should have a high index of suspicion, especially in patients with chronic kidney disease. The present case highlights key physiological mechanisms in the development of hyperkalemia and provides an outline for emergent treatment. In this context, we discuss specific mechanisms of action of available treatments of hyperkalemia. PMID:20570423

Evidence of High Rates of Undiagnosed Asthma in Central Ohio Elementary School children

ERIC Educational Resources Information Center

Clark, Brenda R.; Burkett, S. Amanda; Andridge, Rebecca R.; Buckley, Timothy J.

2013-01-01

Background: In Ohio, 14.5% of 5- to 9-year-olds and 17.3% of 10- to 17-year-olds have asthma. Moreover, there is concern that these numbers may underestimate the true disease burden. We sought to evaluate variability in asthma rates and respiratory symptoms among central Ohio fourth graders as a means to assess potential undiagnosed and…

Body fat distribution in perinatally HIV-infected and HIV-exposed but uninfected children in the era of highly active antiretroviral therapy: outcomes from the Pediatric HIV/AIDS Cohort Study

USDA-ARS?s Scientific Manuscript database

Associations between abnormal body fat distribution and clinical variables are poorly understood in pediatric HIV disease. Our objective was to compare total body fat and its distribution in perinatally HIV-infected and HIV-exposed but uninfected (HEU) children and to evaluate associations with clin...

Linking global climate and temperature variability to widespread amphibian declines putatively caused by disease.

PubMed

Rohr, Jason R; Raffel, Thomas R

2010-05-04

The role of global climate change in the decline of biodiversity and the emergence of infectious diseases remains controversial, and the effect of climatic variability, in particular, has largely been ignored. For instance, it was recently revealed that the proposed link between climate change and widespread amphibian declines, putatively caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), was tenuous because it was based on a temporally confounded correlation. Here we provide temporally unconfounded evidence that global El Niño climatic events drive widespread amphibian losses in genus Atelopus via increased regional temperature variability, which can reduce amphibian defenses against pathogens. Of 26 climate variables tested, only factors associated with temperature variability could account for the spatiotemporal patterns of declines thought to be associated with Bd. Climatic predictors of declines became significant only after controlling for a pattern consistent with epidemic spread (by temporally detrending the data). This presumed spread accounted for 59% of the temporal variation in amphibian losses, whereas El Niño accounted for 59% of the remaining variation. Hence, we could account for 83% of the variation in declines with these two variables alone. Given that global climate change seems to increase temperature variability, extreme climatic events, and the strength of Central Pacific El Niño episodes, climate change might exacerbate worldwide enigmatic declines of amphibians, presumably by increasing susceptibility to disease. These results suggest that changes to temperature variability associated with climate change might be as significant to biodiversity losses and disease emergence as changes to mean temperature.

Changes in Aggressiveness of the Ascochyta lentis Population in Southern Australia

PubMed Central

Davidson, Jennifer; Smetham, Gabriel; Russ, Michelle H.; McMurray, Larn; Rodda, Matthew; Krysinska-Kaczmarek, Marzena; Ford, Rebecca

2016-01-01

Anecdotal evidence identified a change in the reaction of the resistant lentil cv Nipper to ascochyta blight in South Australia in 2010 and subsequent seasons, leading to infection. This study investigated field reactions of lentil cultivars against Ascochyta lentis and the pathogenic variability of the A. lentis population in southern Australia on commonly grown cultivars and on parental germplasm used in the Australian lentil breeding program. Disease data recorded in agronomic and plant breeder field trials from 2005 to 2014 in southern Australia confirmed the change in reaction on the foliage of the previously resistant cvs Nipper and Northfield. Cultivar responses to seed staining from A. lentis did not change. The change in foliar response was confirmed in a series of controlled environment experiments using single, conidium-derived, isolates of A. lentis collected over different years and inoculated onto differential host sets. Specific isolate/cultivar interactions produced a significant range of disease reactions from high to low aggressiveness with a greater percentage of isolates more aggressive on cvs Nipper, Northfield and PBA Flash than previously detected. Specific isolates were tested against Australian lentil cultivars and breeding lines in controlled conditions, again verifying the aggressiveness on cv Nipper. A small percentage of isolates collected prior to the commercial release of cv Nipper were also able to infect this cultivar indicating a natural variability of the A. lentis population which subsequently may have been selected in response to high cropping intensity of cv Nipper. Spore release studies from naturally infested lentil stubbles collected from commercial crops also resulted in a high percentage of infection on the previously resistant cvs Nipper and Northfield. Less than 10% of the lesions developed on the resistant differentials ILL7537 and cv Indianhead. Pathogenic variation within the seasonal populations was not affected by the cultivar from which the stubble was sourced, further indicating a natural variability in aggressiveness. The impact of dominant cultivars in cropping systems and loss of effective disease resistance is discussed. Future studies are needed to determine if levels of aggressiveness among A. lentis isolates are increasing against a range of elite cultivars. PMID:27065073

Accounting for the economic risk caused by variation in disease severity in fungicide dose decisions, exemplified for Mycosphaerella graminicola on winter wheat.

PubMed

Te Beest, D E; Paveley, N D; Shaw, M W; van den Bosch, F

2013-07-01

A method is presented to calculate economic optimum fungicide doses accounting for the risk aversion of growers responding to variability in disease severity between crops. Simple dose-response and disease-yield loss functions are used to estimate net disease-related costs (fungicide cost plus disease-induced yield loss) as a function of dose and untreated severity. With fairly general assumptions about the shapes of the probability distribution of disease severity and the other functions involved, we show that a choice of fungicide dose which minimizes net costs, on average, across seasons results in occasional large net costs caused by inadequate control in high disease seasons. This may be unacceptable to a grower with limited capital. A risk-averse grower can choose to reduce the size and frequency of such losses by applying a higher dose as insurance. For example, a grower may decide to accept "high-loss" years 1 year in 10 or 1 year in 20 (i.e., specifying a proportion of years in which disease severity and net costs will be above a specified level). Our analysis shows that taking into account disease severity variation and risk aversion will usually increase the dose applied by an economically rational grower. The analysis is illustrated with data on Septoria tritici leaf blotch of wheat caused by Mycosphaerella graminicola. Observations from untreated field plots at sites across England over 3 years were used to estimate the probability distribution of disease severities at mid-grain filling. In the absence of a fully reliable disease forecasting scheme, reducing the frequency of high-loss years requires substantially higher doses to be applied to all crops. Disease-resistant cultivars reduce both the optimal dose at all levels of risk and the disease-related costs at all doses.

Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1.

PubMed

Alfadhel, Majid; Alhasan, Khalid A; Alotaibi, Mohammed; Al Fakeeh, Khalid

2012-01-01

Primary hyperoxaluria type 1 (PH1) is characterized by progressive renal insufficiency culminating in end-stage renal disease, and a wide range of clinical features related to systemic oxalosis in different organs. It is caused by autosomal recessive deficiency of alanine:glyoxylate aminotransferase due to a defect in AGXT gene. Two brothers (one 6 months old; the other 2 years old) presented with acute renal failure and urinary tract infection respectively. PH1 was confirmed by high urinary oxalate level, demonstration of oxalate crystals in bone biopsy, and pathogenic homozygous known AGXT gene mutation. Despite the same genetic background, same sex, and shared environment, the outcome of the two siblings differs widely. While one of them died earlier with end-stage renal disease and multiorgan failure caused by systemic oxalosis, the older brother is pyridoxine responsive with normal development and renal function. Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder.

The Association Between Bathing Habits and Severity of Atopic Dermatitis in Children.

PubMed

Koutroulis, Ioannis; Pyle, Tia; Kopylov, David; Little, Anthony; Gaughan, John; Kratimenos, Panagiotis

2016-02-01

Atopic dermatitis is an inflammatory skin disease that frequently affects children. The current recommendations on management using lifestyle modification are highly variable, leading to confusion and uncertainty among patients. To determine current bathing behaviors and the subsequent impact on disease severity. This was an observational cross-sectional study conducted at an urban pediatric emergency department. Parents were asked to fill out a questionnaire concerning the patient's bathing habits. The results were correlated with the atopic dermatitis severity determined by the SCORAD (SCORing Atopic Dermatitis) tool. No difference between variables was found to be significant for bathing frequency, time spent bathing, or use of moisturizers. Multivariate analysis showed that atopic dermatitis severity increased with age greater than 2 years (P = .0004) and with greater bathing duration (P = .001). Atopic dermatitis severity may be associated with a longer duration of bathing. The frequency of bathing does not appear to affect atopic dermatitis severity. © The Author(s) 2015.

Artificial neural networks identify the predictive values of risk factors on the conversion of amnestic mild cognitive impairment.

PubMed

Tabaton, Massimo; Odetti, Patrizio; Cammarata, Sergio; Borghi, Roberta; Monacelli, Fiammetta; Caltagirone, Carlo; Bossù, Paola; Buscema, Massimo; Grossi, Enzo

2010-01-01

The search for markers that are able to predict the conversion of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) is crucial for early mechanistic therapies. Using artificial neural networks (ANNs), 22 variables that are known risk factors of AD were analyzed in 80 patients with aMCI, for a period spanning at least 2 years. The cases were chosen from 195 aMCI subjects recruited by four Italian Alzheimer's disease units. The parameters of glucose metabolism disorder, female gender, and apolipoprotein E epsilon3/epsilon4 genotype were found to be the biological variables with high relevance for predicting the conversion of aMCI. The scores of attention and short term memory tests also were predictors. Surprisingly, the plasma concentration of amyloid-beta (42) had a low predictive value. The results support the utility of ANN analysis as a new tool in the interpretation of data from heterogeneous and distinct sources.

Wildlife disease prevalence in human-modified landscapes.

PubMed

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

2013-05-01

Human-induced landscape change associated with habitat loss and fragmentation places wildlife populations at risk. One issue in these landscapes is a change in the prevalence of disease which may result in increased mortality and reduced fecundity. Our understanding of the influence of habitat loss and fragmentation on the prevalence of wildlife diseases is still in its infancy. What is evident is that changes in disease prevalence as a result of human-induced landscape modification are highly variable. The importance of infectious diseases for the conservation of wildlife will increase as the amount and quality of suitable habitat decreases due to human land-use pressures. We review the experimental and observational literature of the influence of human-induced landscape change on wildlife disease prevalence, and discuss disease transmission types and host responses as mechanisms that are likely to determine the extent of change in disease prevalence. It is likely that transmission dynamics will be the key process in determining a pathogen's impact on a host population, while the host response may ultimately determine the extent of disease prevalence. Finally, we conceptualize mechanisms and identify future research directions to increase our understanding of the relationship between human-modified landscapes and wildlife disease prevalence. This review highlights that there are rarely consistent relationships between wildlife diseases and human-modified landscapes. In addition, variation is evident between transmission types and landscape types, with the greatest positive influence on disease prevalence being in urban landscapes and directly transmitted disease systems. While we have a limited understanding of the potential influence of habitat loss and fragmentation on wildlife disease, there are a number of important areas to address in future research, particularly to account for the variability in increased and decreased disease prevalence. Previous studies have been based on a one-dimensional comparison between unmodified and modified sites. What is lacking are spatially and temporally explicit quantitative approaches which are required to enable an understanding of the range of key causal mechanisms and the reasons for variability. This is particularly important for replicated studies across different host-pathogen systems. Furthermore, there are few studies that have attempted to separate the independent effects of habitat loss and fragmentation on wildlife disease, which are the major determinants of wildlife population dynamics in human-modified landscapes. There is an urgent need to understand better the potential causal links between the processes of human-induced landscape change and the associated influences of habitat fragmentation, matrix hostility and loss of connectivity on an animal's physiological stress, immune response and disease susceptibility. This review identified no study that had assessed the influence of human-induced landscape change on the prevalence of a wildlife sexually transmitted disease. A better understanding of the various mechanisms linking human-induced landscape change and the prevalence of wildlife disease will lead to more successful conservation management outcomes. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.

Acute heart failure in the emergency department: a follow-up study.

PubMed

Fabbri, Andrea; Marchesini, Giulio; Carbone, Giorgio; Cosentini, Roberto; Ferrari, Annamaria; Chiesa, Mauro; Bertini, Alessio; Rea, Federico

2016-02-01

Acute heart failure (AHF) is a major public health issue due to high incidence and poor prognosis. Only a few studies are available on the long-term prognosis and on outcome predictors in the unselected population attending the emergency department (ED) for AHF. We carried out a 1-year follow-up analysis of 1234 consecutive patients from selected Italian EDs from January 2011 to June 2012 for an episode of AHF. Their prognosis and outcome-associated factors were tested by Cox proportional hazard model. Patients' mean age was 84, with 66.0% over 80 years and 56.2% females. Comorbidities were present in over 50% of cases, principally a history of acute coronary syndrome, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, valvular heart disease. Death occurred within 6 h in 24 cases (1.9%). At 30-day follow-up, death was registered in 123 cases (10.0%): 110 cases (89.4%) died of cardiovascular events and 13 (10.6%) of non-cardiovascular causes (cancer, gastrointestinal hemorrhages, sepsis, trauma). At 1-year follow-up, all-cause death was recorded in 50.1% (over 3 out of 4 cases for cardiovascular origin). Six variables (older age, diabetes, systolic arterial pressure <110 mm/Hg, high NT pro-BNP, high troponin levels and impaired cognitive status) were selected as outcome predictors, but with limited discriminant capacity (AUC = 0.649; SE 0.015). Recurrence of AHF was registered in 31.0%. The study identifies a cluster of variables associated with 1-year mortality in AHF, but their predictive capacity is low. Old age and the presence of comorbidities, in particular diabetes are likely to play a major role in dictating the prognosis.

Epidemiological Risk Factors Associated with High Global Frequency of Inapparent Dengue Virus Infections

PubMed Central

Grange, Laura; Simon-Loriere, Etienne; Sakuntabhai, Anavaj; Gresh, Lionel; Paul, Richard; Harris, Eva

2014-01-01

Dengue is a major international public health concern, and the number of outbreaks has escalated greatly. Human migration and international trade and travel are constantly introducing new vectors and pathogens into novel geographic areas. Of particular interest is the extent to which dengue virus (DENV) infections are subclinical or inapparent. Not only may such infections contribute to the global spread of DENV by human migration, but also seroprevalence rates in naïve populations may be initially high despite minimal numbers of detectable clinical cases. As the probability of severe disease is increased in secondary infections, populations may thus be primed, with serious public health consequences following introduction of a new serotype. In addition, pre-existing immunity from inapparent infections may affect vaccine uptake, and the ratio of clinically apparent to inapparent infection could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable, but “inapparent” was the major outcome of infection in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent infection rates. However, one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year, strongly supporting an important role for short-term heterotypic immunity in determining the outcome of infection. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is urgently needed. Inapparent infections need to be considered for their impact on disease severity, transmission dynamics, and vaccine efficacy and uptake. PMID:24966859

Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice: A Japanese Multicenter, Prospective Longitudinal Cohort Study for Achieving a Treat-to-Target Strategy.

PubMed

Koga, Tomohiro; Okada, Akitomo; Fukuda, Takaaki; Hidaka, Toshihiko; Ishii, Tomonori; Ueki, Yukitaka; Kodera, Takao; Nakashima, Munetoshi; Takahashi, Yuichi; Honda, Seiyo; Horai, Yoshiro; Watanabe, Ryu; Okuno, Hiroshi; Aramaki, Toshiyuki; Izumiyama, Tomomasa; Takai, Osamu; Miyashita, Taiichiro; Sato, Shuntaro; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Origuchi, Tomoki; Nakamura, Hideki; Aoyagi, Kiyoshi; Eguchi, Katsumi; Kawakami, Atsushi

2016-04-01

To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice.We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis.CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01-1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17-2.59), RA typical erosion at baseline (95%CI 1.56-21.1), and the introduction of bDMARDs (95%CI 0.06-0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years.We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients' disease durations.

Impact of Hospital Variables on Case Mix Index as a Marker of Disease Severity

PubMed Central

Mendez, Carmen M.; Harrington, Darrell W.; Christenson, Peter

2014-01-01

Abstract Case mix index (CMI) has become a standard indicator of hospital disease severity in the United States and internationally. However, CMI was designed to calculate hospital payments, not to track disease severity, and is highly dependent on documentation and coding accuracy. The authors evaluated whether CMI varied by characteristics affecting hospitals' disease severity (eg, trauma center or not). The authors also evaluated whether CMI was lower at public hospitals than private hospitals, given the diminished financial resources to support documentation enhancement at public hospitals. CMI data for a 14-year period from a large public database were analyzed longitudinally and cross-sectionally to define the impact of hospital variables on average CMI within and across hospital groups. Between 1996 and 2007, average CMI declined by 0.4% for public hospitals, while rising significantly for private for-profit (14%) and nonprofit (6%) hospitals. After the introduction of the Medicare Severity Diagnosis Related Group (MS-DRG) system in 2007, average CMI increased for all 3 hospital types but remained lowest in public vs. private for-profit or nonprofit hospitals (1.05 vs. 1.25 vs. 1.20; P<0.0001). By multivariate analysis, teaching hospitals, level 1 trauma centers, and larger hospitals had higher average CMI, consistent with a marker of disease severity, but only for private hospitals. Public hospitals had lower CMI across all subgroups. Although CMI had some characteristics of a disease severity marker, it was lower across all strata for public hospitals. Hence, caution is warranted when using CMI to adjust for disease severity across public vs. private hospitals. (Population Health Management 2014;17:28–34) PMID:23965045

Do Inflammatory Bowel Disease patients with anxiety and depressive symptoms receive the care they need?

PubMed

Bennebroek Evertsz', F; Thijssens, N A M; Stokkers, P C F; Grootenhuis, M A; Bockting, C L H; Nieuwkerk, P T; Sprangers, M A G

2012-02-01

Inflammatory Bowel Disease (IBD) patients with anxiety and/or depressive symptoms may not receive the care they need. Provision of care requires insight into the factors affecting these psychiatric symptoms. The study was designed to examine the extent to which: (1) IBD patients with anxiety and/or depressive symptoms receive mental treatment and (2) clinical and socio-demographic variables are associated with these symptoms. 231 adult IBD patients (79% response rate), attending a tertiary care center, completed standardized measures on anxiety and depressive symptoms (HADS), quality of life (SF-12) and mental health care use (TIC-P). Diagnosis and disease activity were determined by the gastroenterologist. 43% had high levels of anxiety and/or depressive symptoms, indicative of a psychiatric disorder (HADS ≥ 8), of whom 18% received psychological treatment and 21% used psychotropic medication. In multivariate analysis, high disease activity was associated with anxiety (OR=2.72 | p<0.03) and depression (OR=3.36 | p<0.01), while Crohn's disease was associated with anxiety (OR=2.60 | p<0.03). Despite high levels of anxiety and depressive symptoms and poor quality of life, psychiatric complaints in IBD patients were undertreated. Screening for and treatment of psychiatric symptoms should become an integral part of IBD medical care. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

C3 glomerulonephritis and dense deposit disease share a similar disease course in a large United States cohort of patients with C3 glomerulopathy.

PubMed

Bomback, Andrew S; Santoriello, Dominick; Avasare, Rupali S; Regunathan-Shenk, Renu; Canetta, Pietro A; Ahn, Wooin; Radhakrishnan, Jai; Marasa, Maddalena; Rosenstiel, Paul E; Herlitz, Leal C; Markowitz, Glen S; D'Agati, Vivette D; Appel, Gerald B

2018-04-01

C3 glomerulonephritis (C3GN) and dense deposit disease comprise the two classes of C3 glomerulopathy. Studies from Europe and Asia have aided our understanding of this recently defined disorder, but whether these data apply to a diverse United States patient population remains unclear. We, therefore, reviewed clinical and histopathological data, including generation of a C3 Glomerulopathy Histologic Index to score biopsy activity and chronicity, to determine predictors of progression to end-stage renal disease (ESRD) and advanced chronic kidney disease (CKD) in 111 patients (approximately 35% non-white) with C3 glomerulopathy: 87 with C3GN and 24 with dense deposit disease. Complement-associated gene variants and autoantibodies were detected in 24% and 35% of screened patients, respectively. Our C3 Glomerulopathy Histologic Index denoted higher activity in patients with C3GN and higher chronicity in patients with dense deposit disease. Over an average of 72 months of follow-up, remission occurred in 38% of patients with C3GN and 25% of patients with dense deposit disease. Progression to late-stage CKD and ESRD was common, with no differences between C3GN (39%) and dense deposit disease (42%). In multivariable models, the strongest predictors for progression were estimated glomerular filtration rate at diagnosis (clinical variables model) and tubular atrophy/interstitial fibrosis (histopathology variables model). Using our C3 Glomerulopathy Histologic Index, both total activity and total chronicity scores emerged as the strongest predictors of progression. Thus, in a large, diverse American cohort of patients with C3 glomerulopathy, there is a high rate of progression to CKD and ESRD with no differences between C3GN and dense deposit disease. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Impact of climate variability on vector-borne disease transmission

USDA-ARS?s Scientific Manuscript database

We will discuss the impact of climate variability on vector borne diseases and demonstrate that global climate teleconnections can be used to anticipate and forecast, in the case of Rift Valley fever, epidemics and epizootics. In this context we will examine significant worldwide weather anomalies t...

A composite model including visfatin, tissue polypeptide-specific antigen, hyaluronic acid, and hematological variables for the diagnosis of moderate-to-severe fibrosis in nonalcoholic fatty liver disease: a preliminary study.

PubMed

Chwist, Alina; Hartleb, Marek; Lekstan, Andrzej; Kukla, Michał; Gutkowski, Krzysztof; Kajor, Maciej

2014-01-01

Histopathological risk factors for end-stage liver failure in patients with nonalcoholic fatty liver disease (NAFLD) include nonalcoholic steatohepatitis (NASH) and advanced liver fibrosis. There is a need for noninvasive diagnostic methods for these 2 conditions. The aim of this study was to investigate new laboratory variables with a predictive potential to detect advanced fibrosis (stages 2 and 3) in NAFLD. The study involved 70 patients with histologically proven NAFLD of varied severity. Additional laboratory variables included zonulin, haptoglobin, visfatin, adiponectin, leptin, tissue polypeptide-specific antigen (TPSA), hyaluronic acid, and interleukin 6. Patients with NASH (NAFLD activity score of ≥5) had significantly higher HOMA-IR values and serum levels of visfatin, haptoglobin, and zonulin as compared with those without NASH on histological examination. Advanced fibrosis was found in 16 patients (22.9%) and the risk factors associated with its prevalence were age, the ratio of erythrocyte count to red blood cell distribution width, platelet count, and serum levels of visfatin and TPSA. Based on these variables, we constructed a scoring system that differentiated between NAFLD patients with and without advanced fibrosis with a sensitivity of 75% and specificity of 100% (area under the receiver operating characteristic curve, 0.93). The scoring system based on the above variables allows to predict advanced fibrosis with high sensitivity and specificity. However, its clinical utility should be verified in further studies involving a larger number of patients.

Use of signal analysis of heart sounds and murmurs to assess severity of mitral valve regurgitation attributable to myxomatous mitral valve disease in dogs.

PubMed

Ljungvall, Ingrid; Ahlstrom, Christer; Höglund, Katja; Hult, Peter; Kvart, Clarence; Borgarelli, Michele; Ask, Per; Häggström, Jens

2009-05-01

To investigate use of signal analysis of heart sounds and murmurs in assessing severity of mitral valve regurgitation (mitral regurgitation [MR]) in dogs with myxomatous mitral valve disease (MMVD). 77 client-owned dogs. Cardiac sounds were recorded from dogs evaluated by use of auscultatory and echocardiographic classification systems. Signal analysis techniques were developed to extract 7 sound variables (first frequency peak, murmur energy ratio, murmur duration > 200 Hz, sample entropy and first minimum of the auto mutual information function of the murmurs, and energy ratios of the first heart sound [S1] and second heart sound [S2]). Significant associations were detected between severity of MR and all sound variables, except the energy ratio of S1. An increase in severity of MR resulted in greater contribution of higher frequencies, increased signal irregularity, and decreased energy ratio of S2. The optimal combination of variables for distinguishing dogs with high-intensity murmurs from other dogs was energy ratio of S2 and murmur duration > 200 Hz (sensitivity, 79%; specificity, 71%) by use of the auscultatory classification. By use of the echocardiographic classification, corresponding variables were auto mutual information, first frequency peak, and energy ratio of S2 (sensitivity, 88%; specificity, 82%). Most of the investigated sound variables were significantly associated with severity of MR, which indicated a powerful diagnostic potential for monitoring MMVD. Signal analysis techniques could be valuable for clinicians when performing risk assessment or determining whether special care and more extensive examinations are required.

Meteorological influences on the interannual variability of meningitis incidence in northwest Nigeria.

NASA Astrophysics Data System (ADS)

Abdussalam, Auwal; Monaghan, Andrew; Dukic, Vanja; Hayden, Mary; Hopson, Thomas; Leckebusch, Gregor

2013-04-01

Northwest Nigeria is a region with high risk of bacterial meningitis. Since the first documented epidemic of meningitis in Nigeria in 1905, the disease has been endemic in the northern part of the country, with epidemics occurring regularly. In this study we examine the influence of climate on the interannual variability of meningitis incidence and epidemics. Monthly aggregate counts of clinically confirmed hospital-reported cases of meningitis were collected in northwest Nigeria for the 22-year period spanning 1990-2011. Several generalized linear statistical models were fit to the monthly meningitis counts, including generalized additive models. Explanatory variables included monthly records of temperatures, humidity, rainfall, wind speed, sunshine and dustiness from weather stations nearest to the hospitals, and a time series of polysaccharide vaccination efficacy. The effects of other confounding factors -- i.e., mainly non-climatic factors for which records were not available -- were estimated as a smooth, monthly-varying function of time in the generalized additive models. Results reveal that the most important explanatory climatic variables are mean maximum monthly temperature, relative humidity and dustiness. Accounting for confounding factors (e.g., social processes) in the generalized additive models explains more of the year-to-year variation of meningococcal disease compared to those generalized linear models that do not account for such factors. Promising results from several models that included only explanatory variables that preceded the meningitis case data by 1-month suggest there may be potential for prediction of meningitis in northwest Nigeria to aid decision makers on this time scale.

Perceptions of risk of coronary heart disease among people living with type 2 diabetes mellitus.

PubMed

Ammouri, Ali Ahmad; Abu Raddaha, Ahmad H; Natarajan, Jansi; D'Souza, Melba Sheila

2018-02-01

Our aim is to assess perception of risk of developing coronary heart disease and to examine its associations with individuals' characteristics and health behaviours among Omani people with type 2 diabetes mellitus (T2DM). Evaluating perceptions of being at risk of developing a disease may give insight into health promotion behaviours. People with diabetes are at high risk of coronary heart disease. The management of diabetes mellitus should include prevention and control of coronary heart disease. A cross-sectional correlational study was conducted. A convenience sample of 160 adults with T2DM was invited to participate in this study between November 2014 and March 2015. Descriptive and regression analyses were performed to examine associations between study variables. Perception of risk of developing coronary heart disease was significantly associated with low educational level (β = 0.191, P < .05), low income (β = 0.201, P < .05), and high level of knowledge about diabetes mellitus (β = 0.200, P < .05). People with T2DM who perceived coronary heart disease as having few moderate known outcomes and consequences reported consuming healthy diet more frequently. Teaching people with T2DM about the risk of developing coronary heart disease is essential as it could motivate them to perform health promotion behaviours, which may assist in controlling and reducing coronary heart disease. © 2017 John Wiley & Sons Australia, Ltd.

Cardiorespiratory interactions in humans and animals: Rhythms for life.

PubMed

Elstad, Maja; O'Callaghan, Erin L; Smith, Alexander J; Ben-Tal, A; Ramchandra, Rohit

2018-03-09

The cardiorespiratory system exhibits oscillations from a range of sources. One of the most studied oscillations is heart rate variability, which is thought to be beneficial and can serve as an index of a healthy cardiovascular system. Heart rate variability is dampened in many diseases including depression, autoimmune diseases, hypertension and heart failure. Thus, understanding the interactions that lead to heart rate variability, and its physiological role, could help with prevention, diagnosis and treatment of cardiovascular diseases. In this review we consider three types of cardiorespiratory interactions; Respiratory Sinus Arrhythmia - variability in heart rate at the frequency of breathing, Cardioventilatory Coupling - synchronization between the heart beat and the onset of inspiration, and Respiratory Stroke Volume Synchronization - constant phase difference between the right and the left stroke volumes over one respiratory cycle. While the exact physiological role of these oscillations continues to be debated, the redundancies in the mechanisms responsible for its generation and its strong evolutionary conservation point to the importance of cardiorespiratory interactions. The putative mechanisms driving cardiorespiratory oscillations as well as the physiological significance of these oscillations will be reviewed. We suggest that cardiorespiratory interactions have the capacity to both dampen the variability in systemic blood flow as well as improve the efficiency of work done by the heart while maintaining physiological levels of arterial CO 2 . Given that reduction in variability is a prognostic indicator of disease, we argue that restoration of this variability via pharmaceutical or device-based approaches may be beneficial in prolonging life.

Observer variability in the assessment of CT coronary angiography and coronary artery calcium score: substudy of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial

PubMed Central

Williams, Michelle C; Golay, Saroj K; Hunter, Amanda; Weir-McCall, Jonathan R; Mlynska, Lucja; Dweck, Marc R; Uren, Neal G; Reid, John H; Lewis, Steff C; Berry, Colin; van Beek, Edwin J R; Roditi, Giles; Newby, David E; Mirsadraee, Saeed

2015-01-01

Introduction Observer variability can influence the assessment of CT coronary angiography (CTCA) and the subsequent diagnosis of angina pectoris due to coronary heart disease. Methods We assessed 210 CTCAs from the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial for intraobserver and interobserver variability. Calcium score, coronary angiography and image quality were evaluated. Coronary artery disease was defined as none (<10%), mild (10–49%), moderate (50–70%) and severe (>70%) luminal stenosis and classified as no (<10%), non-obstructive (10–70%) or obstructive (>70%) coronary artery disease. Post-CTCA diagnosis of angina pectoris due to coronary heart disease was classified as yes, probable, unlikely or no. Results Patients had a mean body mass index of 29 (28, 30) kg/m2, heart rate of 58 (57, 60)/min and 62% were men. Intraobserver and interobserver agreements for the presence or absence of coronary artery disease were excellent (95% agreement, κ 0.884 (0.817 to 0.951) and good (91%, 0.791 (0.703 to 0.879)). Intraobserver and interobserver agreement for the presence or absence of angina pectoris due to coronary heart disease were excellent (93%, 0.842 (0.918 to 0.755) and good (86%, 0.701 (0.799 to 0.603)), respectively. Observer variability of calcium score was excellent for calcium scores below 1000. More segments were categorised as uninterpretable with 64-multidetector compared to 320-multidetector CTCA (10.1% vs 2.6%, p<0.001) but there was no difference in observer variability. Conclusions Multicentre multidetector CTCA has excellent agreement in patients under investigation for suspected angina due to coronary heart disease. Trial registration number NCT01149590. PMID:26019881

Diagnosis and treatment of high density lipoprotein deficiency.

PubMed

Schaefer, Ernst J; Anthanont, Pimjai; Diffenderfer, Margaret R; Polisecki, Eliana; Asztalos, Bela F

Low serum high density lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease. There is marked variability in laboratory and clinical presentation, and DNA analysis is necessary for diagnosis. These patients can develop premature CVD, neuropathy, kidney failure, neuropathy, hepatosplenomegaly and anemia. Treatment should be directed at optimizing all non-HDL risk factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Prevention of post-operative recurrence of Crohn's disease.

PubMed

Vaughn, Byron Philip; Moss, Alan Colm

2014-02-07

Endoscopic and clinical recurrence of Crohn's disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

The role of climate and out-of-Africa migration in the frequencies of risk alleles for 21 human diseases.

PubMed

Blair, Lily M; Feldman, Marcus W

2015-07-14

Demography and environmental adaptation can affect the global distribution of genetic variants and possibly the distribution of disease. Population heterozygosity of single nucleotide polymorphisms has been shown to decrease strongly with distance from Africa and this has been attributed to the effect of serial founding events during the migration of humans out of Africa. Additionally, population allele frequencies have been shown to change due to environmental adaptation. Here, we investigate the relationship of Out-of-Africa migration and climatic variables to the distribution of risk alleles for 21 diseases. For each disease, we computed the regression of average heterozygosity and average allele frequency of the risk alleles with distance from Africa and 9 environmental variables. We compared these regressions to a null distribution created by regressing statistics for SNPs not associated with disease on distance from Africa and these environmental variables. Additionally, we used Bayenv 2.0 to assess the signal of environmental adaptation associated with individual risk SNPs. For those SNPs in HGDP and HapMap that are risk alleles for type 2 diabetes, we cannot reject that their distribution is as expected from Out-of-Africa migration. However, the allelic statistics for many other diseases correlate more closely with environmental variables than would be expected from the serial founder effect and show signals of environmental adaptation. We report strong environmental interactions with several autoimmune diseases, and note a particularly strong interaction between asthma and summer humidity. Additionally, we identified several risk genes with strong environmental associations. For most diseases, migration does not explain the distribution of risk alleles and the worldwide pattern of allele frequencies for some diseases may be better explained by environmental associations, which suggests that some selection has acted on these diseases.

A spatial scan statistic for nonisotropic two-level risk cluster.

PubMed

Li, Xiao-Zhou; Wang, Jin-Feng; Yang, Wei-Zhong; Li, Zhong-Jie; Lai, Sheng-Jie

2012-01-30

Spatial scan statistic methods are commonly used for geographical disease surveillance and cluster detection. The standard spatial scan statistic does not model any variability in the underlying risks of subregions belonging to a detected cluster. For a multilevel risk cluster, the isotonic spatial scan statistic could model a centralized high-risk kernel in the cluster. Because variations in disease risks are anisotropic owing to different social, economical, or transport factors, the real high-risk kernel will not necessarily take the central place in a whole cluster area. We propose a spatial scan statistic for a nonisotropic two-level risk cluster, which could be used to detect a whole cluster and a noncentralized high-risk kernel within the cluster simultaneously. The performance of the three methods was evaluated through an intensive simulation study. Our proposed nonisotropic two-level method showed better power and geographical precision with two-level risk cluster scenarios, especially for a noncentralized high-risk kernel. Our proposed method is illustrated using the hand-foot-mouth disease data in Pingdu City, Shandong, China in May 2009, compared with two other methods. In this practical study, the nonisotropic two-level method is the only way to precisely detect a high-risk area in a detected whole cluster. Copyright © 2011 John Wiley & Sons, Ltd.