Effect of conjugal bereavement on mortality of the bereaved spouse in participants of the Renfrew/Paisley Study

PubMed Central

Hart, Carole L; Hole, David J; Lawlor, Debbie A; Smith, George Davey; Lever, Tony F

2007-01-01

Objectives To investigate how loss of a spouse affects mortality risk in the bereaved partner. Design and setting Prospective cohort study in Renfrew and Paisley in Scotland. Participants 4395 married couples aged 45–64 years when the study was carried out between 1972 and 1976. Methods The date of bereavement for the bereaved spouse was the date of death of his or her spouse. Bereavement could occur at any time during the follow‐up period, so it was considered as a time‐dependent exposure variable and the Cox proportional hazards model for time‐dependent variables was used. The relative rate (RR) of mortality was calculated for bereaved versus non‐bereaved spouses and adjusted for confounding variables. Main outcome measures Causes of death to 31 March 2004. Results Bereaved participants were at higher risk than non‐bereaved participants of dying from any cause (RR 1.27; 95% CI 1.2 to 1.35). These risks remained but were attenuated after adjustment for confounding variables. There were raised RRs for bereaved participants dying of cardiovascular disease, coronary heart disease, stroke, all cancer, lung cancer, smoking‐related cancer, and accidents or violence. After adjustment for confounding variables, RRs remained higher for bereaved participants for all these causes except for mortality from lung cancer. There was no strong statistical evidence that the increased risks of death associated with bereavement changed with time after bereavement. Conclusions Conjugal bereavement, in addition to existing risk factors, is related to mortality risk for major causes of death. PMID:17435215

[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.

Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa

PubMed Central

Daiger, Stephen P.; Bowne, Sara J.; Sullivan, Lori S.

2015-01-01

Retinitis pigmentosa (RP) has a prevalence of approximately one in 4000; 25%–30% of these cases are autosomal dominant retinitis pigmentosa (adRP). Like other forms of inherited retinal disease, adRP is exceptionally heterogeneous. Mutations in more than 25 genes are known to cause adRP, more than 1000 mutations have been reported in these genes, clinical findings are highly variable, and there is considerable overlap with other types of inherited disease. Currently, it is possible to detect disease-causing mutations in 50%–75% of adRP families in select populations. Genetic diagnosis of adRP has advantages over other forms of RP because segregation of disease in families is a useful tool for identifying and confirming potentially pathogenic variants, but there are disadvantages too. In addition to identifying the cause of disease in the remaining 25% of adRP families, a central challenge is reconciling clinical diagnosis, family history, and molecular findings in patients and families. PMID:25304133

Comparison of short-term associations with meteorological variables between COPD and pneumonia hospitalization among the elderly in Hong Kong—a time-series study

NASA Astrophysics Data System (ADS)

Lam, Holly Ching-yu; Chan, Emily Ying-yang; Goggins, William Bernard

2018-05-01

Pneumonia and chronic obstructive pulmonary diseases (COPD) are the commonest causes of respiratory hospitalization among older adults. Both diseases have been reported to be associated with ambient temperature, but the associations have not been compared between the diseases. Their associations with other meteorological variables have also not been well studied. This study aimed to evaluate the associations between meteorological variables, pneumonia, and COPD hospitalization among adults over 60 and to compare these associations between the diseases. Daily cause-specific hospitalization counts in Hong Kong during 2004-2011 were regressed on daily meteorological variables using distributed lag nonlinear models. Associations were compared between diseases by ratio of relative risks. Analyses were stratified by season and age group (60-74 vs. ≥ 75). In hot season, high temperature (> 28 °C) and high relative humidity (> 82%) were statistically significantly associated with more pneumonia in lagged 0-2 and lagged 0-10 days, respectively. Pneumonia hospitalizations among the elderly (≥ 75) also increased with high solar radiation and high wind speed. During the cold season, consistent hockey-stick associations with temperature and relative humidity were found for both admissions and both age groups. The minimum morbidity temperature and relative humidity were at about 21-22 °C and 82%. The lagged effects of low temperature were comparable for both diseases (lagged 0-20 days). The low-temperature-admissions associations with COPD were stronger and were strongest among the elderly. This study found elevated pneumonia and COPD admissions risks among adults ≥ 60 during periods of extreme weather conditions, and the associations varied by season and age group. Vulnerable groups should be advised to avoid exposures, such as staying indoor and maintaining satisfactory indoor conditions, to minimize risks.

Characteristics and consequences of root diseases in forests of Western North America

Treesearch

D.J. Goheen; W.J. Otrosina

1998-01-01

Root diseases are somewhat mysterious. Operating as they do within the soil, it is difficult to actually view root pathogens or follow their progress in causing disease. The signs and symptoms that they produce can be quite subtle and variable. Just identifying which pathogen occurs in a specific situation is often challenging. Nevertheless, in the past two decades,...

Discovery of Antinuclear Antibodies in Pigs Infected with Porcine Circovirus Type 2

USDA-ARS?s Scientific Manuscript database

Introduction. Porcine circovirus type 2 (PCV2) causes post-weaning-multisystemic-wasting-syndrome (PMWS), a swine disease first observed in Canada in 1991 (1). It is characterized by general wasting, respiratory disease, jaundice and pallor in young pigs resulting in production losses and variable...

[Small airway diseases and immune deficiency].

PubMed

Burgel, P-R; Bergeron, A; Knoop, C; Dusser, D

2016-02-01

Innate or acquired immune deficiency may show respiratory manifestations, often characterized by small airway involvement. The purpose of this article is to provide an overview of small airway disease across the major causes of immune deficiency. In patients with common variable immune deficiency, recurrent lower airway infections may lead to bronchiolitis and bronchiectasis. Follicular and/or granulomatous bronchiolitis of unknown origin may also occur. Bronchiolitis obliterans is the leading cause of death after the first year in patients with lung transplantation. Bronchiolitis obliterans also occurs in patients with allogeneic haematopoietic stem cell transplantation, especially in the context of systemic graft-versus-host disease. Small airway diseases have different clinical expression and pathophysiology across various causes of immune deficiency. A better understanding of small airways disease pathogenesis in these settings may lead to the development of novel targeted therapies. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Cause-specific mortality according to urine albumin creatinine ratio in the general population.

PubMed

Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Ahluwalia, Tarunveer Singh; Rossing, Peter; Jørgensen, Torben; Thuesen, Betina Heinsbæk; Pisinger, Charlotta; Rasmussen, Knud; Linneberg, Allan

2014-01-01

Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortality, cardiovascular disease and diabetes in observational studies. Whether a high UACR is also associated with other causes of death is unclear. We investigated the association between UACR and cause-specific mortality. We included a total of 9,125 individuals from two population-based studies, Monica10 and Inter99, conducted in 1993-94 and 1999-2001, respectively. Urine albumin creatinine ratio was measured from spot urine samples by standard methods. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2010. There were a total of 920 deaths, and the median follow-up was 11.3 years. Multivariable Cox regression analyses with age as underlying time axis showed statistically significant positive associations between UACR status and risk of all-cause mortality, endocrine nutritional and metabolic diseases, mental and behavioural disorders, diseases of the circulatory system, and diseases of the respiratory system with hazard ratios 1.56, 6.98, 2.34, 2.03, and 1.91, for the fourth UACR compared with the first, respectively. Using UACR as a continuous variable, we also found a statistically significant positive association with risk of death caused by diseases of the digestive system with a hazard ratio of 1.02 per 10 mg/g higher UACR. We found statistically significant positive associations between baseline UACR and death from all-cause mortality, endocrine nutritional and metabolic diseases, and diseases of the circulatory system and possibly mental and behavioural disorders, and diseases of the respiratory and digestive system.

Elastic-net regularization approaches for genome-wide association studies of rheumatoid arthritis.

PubMed

Cho, Seoae; Kim, Haseong; Oh, Sohee; Kim, Kyunga; Park, Taesung

2009-12-15

The current trend in genome-wide association studies is to identify regions where the true disease-causing genes may lie by evaluating thousands of single-nucleotide polymorphisms (SNPs) across the whole genome. However, many challenges exist in detecting disease-causing genes among the thousands of SNPs. Examples include multicollinearity and multiple testing issues, especially when a large number of correlated SNPs are simultaneously tested. Multicollinearity can often occur when predictor variables in a multiple regression model are highly correlated, and can cause imprecise estimation of association. In this study, we propose a simple stepwise procedure that identifies disease-causing SNPs simultaneously by employing elastic-net regularization, a variable selection method that allows one to address multicollinearity. At Step 1, the single-marker association analysis was conducted to screen SNPs. At Step 2, the multiple-marker association was scanned based on the elastic-net regularization. The proposed approach was applied to the rheumatoid arthritis (RA) case-control data set of Genetic Analysis Workshop 16. While the selected SNPs at the screening step are located mostly on chromosome 6, the elastic-net approach identified putative RA-related SNPs on other chromosomes in an increased proportion. For some of those putative RA-related SNPs, we identified the interactions with sex, a well known factor affecting RA susceptibility.

Environmental determinants of severity in sickle cell disease

PubMed Central

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

2015-01-01

Sickle cell disease causes acute and chronic illness, and median life expectancy is reduced by at least 30 years in all countries, with greater reductions in low-income countries. There is a wide spectrum of severity, with some patients having no symptoms and others suffering frequent, life-changing complications. Much of this variability is unexplained, despite increasingly sophisticated genetic studies. Environmental factors, including climate, air quality, socio-economics, exercise and infection, are likely to be important, as demonstrated by the stark differences in outcomes between patients in Africa and USA/Europe. The effects of weather vary with geography, although most studies show that exposure to cold or wind increases hospital attendance with acute pain. Most of the different air pollutants are closely intercorrelated, and increasing overall levels seem to correlate with increased hospital attendance, although higher concentrations of atmospheric carbon monoxide may offer some benefit for patients with sickle cell disease. Exercise causes some adverse physiological changes, although this may be off-set by improvements in cardiovascular health. Most sickle cell disease patients live in low-income countries and socioeconomic factors are undoubtedly important, but little studied beyond documenting that sickle cell disease is associated with decreases in some measures of social status. Infections cause many of the differences in outcomes seen across the world, but again these effects are relatively poorly understood. All the above factors are likely to account for much of the pathology and variability of sickle cell disease, and large prospective studies are needed to understand these effects better. PMID:26341524

[Anaemia as a cause of haemodynamic angina in a patient with chronic ischaemic heart disease].

PubMed

Miguéns Blanco, I; Bravo Amaro, M

2014-01-01

Ischaemic heart disease is the leading cause of mortality and morbidity and one of the primary causes of morbidity in Spain. The variability in the clinical presentation of this condition at both primary care and emergency services level requires a careful history and a thorough physical examination. In the case presented, the main symptoms of angina and dyspnea reported in the anamnesis, and the obvious pallor in the physical examination, were the key data to identify anaemia as a cause of angina. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Allelic and Phenotypic Heterogeneity in ABCA4 mutations

PubMed Central

Burke, Tomas R; Tsang, Stephen H

2011-01-01

Since the discovery of the ABCA4 gene as the cause of autosomal recessive Stargardt disease/fundus flavimaculatus much has been written of the phenotypic variability in ABCA4 retinopathy. In this review the authors discuss the findings seen on examination and the disease features detected using various clinical tests. Important differential diagnoses are presented and unusual presentations of ABCA4 disease highlighted. PMID:21510770

Development of single chain variable fragment (scFv) antibodies against Xylella fastidiosa subsp. pauca by phage display

USDA-ARS?s Scientific Manuscript database

Xylella fastidiosa is a member of the gamma proteobacteria. It is fastidious, insect-vectored and xylem-limited and causes a variety of diseases, some severe, on a wide range of economically important perennial crops, including grape and citrus. Xylella fastidiosa subsp pauca causes citrus variegat...

Dynamic changes in the rice blast population in the USA over six decades

USDA-ARS?s Scientific Manuscript database

Rice blast disease caused by Magnaporthe oryzae is one of the most destructive diseases of rice. Field isolates of M. oryzae rapidly adapt to the hosts and climate. Tracking the genetic and pathogenic variability of the field isolates is essential to understand how M. oryzae interacts with hosts an...

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 ...

Virology, Immunology, and Clinical Course of HIV Infection.

ERIC Educational Resources Information Center

McCutchan, J. Allen

1990-01-01

Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

The pathogenesis of bornaviral diseases in mammals.

PubMed

Tizard, Ian; Ball, Judith; Stoica, George; Payne, Susan

2016-12-01

Natural bornavirus infections and their resulting diseases are largely restricted to horses and sheep in Central Europe. The disease also occurs naturally in cats, and can be induced experimentally in laboratory rodents and numerous other mammals. Borna disease virus-1 (BoDV-1), the cause of most cases of mammalian Borna disease, is a negative-stranded RNA virus that replicates within the nucleus of target cells. It causes severe, often lethal, encephalitis in susceptible species. Recent events, especially the discovery of numerous new species of bornaviruses in birds and a report of an acute, lethal bornaviral encephalitis in humans, apparently acquired from squirrels, have revived interest in this remarkable family of viruses. The clinical manifestations of the bornaviral diseases are highly variable. Thus, in addition to acute lethal encephalitis, they can cause persistent neurologic disease associated with diverse behavioral changes. They also cause a severe retinitis resulting in blindness. In this review, we discuss both the pathological lesions observed in mammalian bornaviral disease and the complex pathogenesis of the neurologic disease. Thus infected neurons may be destroyed by T-cell-mediated cytotoxicity. They may die as a result of excessive inflammatory cytokine release from microglia. They may also die as a result of a 'glutaminergic storm' due to a failure of infected astrocytes to regulate brain glutamate levels.

Exercise Benefits Coronary Heart Disease.

PubMed

Wang, Lei; Ai, Dongmei; Zhang, Ning

2017-01-01

Coronary heart disease (CHD) is a group of diseases that include: no symptoms, angina, myocardial infarction, ischemia cardiomyopathy and sudden cardiac death. And it results from multiple risks factors consisting of invariable factors (e.g. age, gender, etc.) and variable factors (e.g. dyslipidemia, hypertension, diabetes, smoking, etc.). Meanwhile, CHD could cause impact not only localized in the heart, but also on pulmonary function, whole-body skeletal muscle function, activity ability, psychological status, etc. Nowadays, CHD has been the leading cause of death in the world. However, many clinical researches showed that exercise training plays an important role in cardiac rehabilitation and can bring a lot of benefits for CHD patients.

Environmental Variation Generates Environmental Opportunist Pathogen Outbreaks.

PubMed

Anttila, Jani; Kaitala, Veijo; Laakso, Jouni; Ruokolainen, Lasse

2015-01-01

Many socio-economically important pathogens persist and grow in the outside host environment and opportunistically invade host individuals. The environmental growth and opportunistic nature of these pathogens has received only little attention in epidemiology. Environmental reservoirs are, however, an important source of novel diseases. Thus, attempts to control these diseases require different approaches than in traditional epidemiology focusing on obligatory parasites. Conditions in the outside-host environment are prone to fluctuate over time. This variation is a potentially important driver of epidemiological dynamics and affect the evolution of novel diseases. Using a modelling approach combining the traditional SIRS models to environmental opportunist pathogens and environmental variability, we show that epidemiological dynamics of opportunist diseases are profoundly driven by the quality of environmental variability, such as the long-term predictability and magnitude of fluctuations. When comparing periodic and stochastic environmental factors, for a given variance, stochastic variation is more likely to cause outbreaks than periodic variation. This is due to the extreme values being further away from the mean. Moreover, the effects of variability depend on the underlying biology of the epidemiological system, and which part of the system is being affected. Variation in host susceptibility leads to more severe pathogen outbreaks than variation in pathogen growth rate in the environment. Positive correlation in variation on both targets can cancel the effect of variation altogether. Moreover, the severity of outbreaks is significantly reduced by increase in the duration of immunity. Uncovering these issues helps in understanding and controlling diseases caused by environmental pathogens.

Human mortality seasonality in Castile-León, Spain, between 1980 and 1998: the influence of temperature, pressure and humidity

NASA Astrophysics Data System (ADS)

Fernández-Raga, María; Tomás, Clemente; Fraile, Roberto

2010-07-01

This study was carried out in the region of Castile and Leon, Spain, from 1980 to 1998 and analyzes the relationship between the number of monthly deaths caused by cardiovascular, respiratory and digestive diseases and three meteorological variables: temperature, pressure and humidity. One of the innovations in this study is the application of principal component analysis in a way that differs from its usual application: one single series representing the whole region was constructed for each meteorological variable from the series of eight weather stations. Annual and seasonal mortality trends were also studied. Cardiovascular diseases are the leading cause of death in Castile and Leon. The mortality related to cardiovascular, respiratory and digestive systems shows a statistically significant rising trend across the study period (an annual increase of 6, 16 and 4‰, respectively). The pressure at which mortality is lowest is approximately the same for all causes of death (about 915 hPa), but temperature values vary greatly (16.8-19.7°C for the mean, 10.9-18.1°C for the minimum, and 24.1-27.2°C for the maximum temperature). The most comfortable temperatures for patients with cardiovascular diseases (16.8°C) are apparently lower than those for patients with respiratory diseases (18.1°C), which are, in turn, lower than in the case of diseases of the digestive system (19.7°C). Finally, the optimal humidity for patients with respiratory diseases is the lowest (24%) among the diseases, and the highest (51%) corresponds to diseases of the digestive system, while the optimal relative humidity for the cardiovascular system is 45%.

Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis

PubMed Central

2013-01-01

Background The relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found. Methods A pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities. Results Twenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer’s disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer’s disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes. Conclusions This study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered. PMID:23679869

Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis.

PubMed

Martinez-Beneito, Miguel A; Zurriaga, Oscar; Botella-Rocamora, Paloma; Marí-Dell'Olmo, Marc; Nolasco, Andreu; Moncho, Joaquín; Daponte, Antonio; Domínguez-Berjón, M Felicitas; Gandarillas, Ana; Martos, Carmen; Montoya, Imanol; Sánchez-Villegas, Pablo; Taracido, Margarita; Borrell, Carme

2013-05-16

The relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found. A pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities. Twenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer's disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer's disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes. This study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered.

Pathogenesis and diagnostic criteria for rickets and osteomalacia - proposal by an expert panel supported by Ministry of Health, Labour and Welfare, Japan, The Japanese Society for Bone and Mineral Research and The Japan Endocrine Society.

PubMed

Fukumoto, Seiji; Ozono, Keiichi; Michigami, Toshimi; Minagawa, Masanori; Okazaki, Ryo; Sugimoto, Toshitsugu; Takeuchi, Yasuhiro; Matsumoto, Toshio

2015-01-01

Rickets and osteomalacia are diseases characterized by impaired mineralization of bone matrix. Recent investigations revealed that the causes for rickets and osteomalacia are quite variable. While these diseases can severely impair the quality of life of the affected patients, rickets and osteomalacia can be completely cured or at least respond to treatment when properly diagnosed and treated according to the specific causes. On the other hand, there are no standard criteria to diagnose rickets or osteomalacia nationally and internationally. Therefore, we summarize the definition and pathogenesis of rickets and osteomalacia, and propose the diagnostic criteria and a flowchart for the differential diagnosis of various causes for these diseases. We hope that these criteria and flowchart are clinically useful for the proper diagnosis and management of patients with these diseases.

Pathogenesis and diagnostic criteria for rickets and osteomalacia--proposal by an expert panel supported by the Ministry of Health, Labour and Welfare, Japan, the Japanese Society for Bone and Mineral Research, and the Japan Endocrine Society.

PubMed

Fukumoto, Seiji; Ozono, Keiichi; Michigami, Toshimi; Minagawa, Masanori; Okazaki, Ryo; Sugimoto, Toshitsugu; Takeuchi, Yasuhiro; Matsumoto, Toshio

2015-09-01

Rickets and osteomalacia are diseases characterized by impaired mineralization of bone matrix. Recent investigations have revealed that the causes of rickets and osteomalacia are quite variable. Although these diseases can severely impair the quality of life of affected patients, rickets and osteomalacia can be completely cured or at least respond to treatment when properly diagnosed and treated according to the specific causes. On the other hand, there are no standard criteria to diagnose rickets or osteomalacia nationally and internationally. Therefore, we summarize the definition and pathogenesis of rickets and osteomalacia, and propose diagnostic criteria and a flowchart for the differential diagnosis of various causes of these diseases. We hope that these criteria and the flowchart are clinically useful for the proper diagnosis and management of these diseases.

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.

The cross wavelet analysis of dengue fever variability influenced by meteorological conditions

NASA Astrophysics Data System (ADS)

Lin, Yuan-Chien; Yu, Hwa-Lung; Lee, Chieh-Han

2015-04-01

The multiyear variation of meteorological conditions induced by climate change causes the changing diffusion pattern of infectious disease and serious epidemic situation. Among them, dengue fever is one of the most serious vector-borne diseases distributed in tropical and sub-tropical regions. Dengue virus is transmitted by several species of mosquito and causing lots amount of human deaths every year around the world. The objective of this study is to investigate the impact of meteorological variables to the temporal variation of dengue fever epidemic in southern Taiwan. Several extreme and average indices of meteorological variables, i.e. temperature and humidity, were used for this analysis, including averaged, maximum and minimum temperature, and average rainfall, maximum 1-hr rainfall, and maximum 24-hr rainfall. This study plans to identify and quantify the nonlinear relationship of meteorological variables and dengue fever epidemic, finding the non-stationary time-frequency relationship and phase lag effects of those time series from 1998-2011 by using cross wavelet method. Results show that meteorological variables all have a significant time-frequency correlation region to dengue fever epidemic in frequency about one year (52 weeks). The associated phases can range from 0 to 90 degrees (0-13 weeks lag from meteorological factors to dengue incidences). Keywords: dengue fever, cross wavelet analysis, meteorological factor

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...

Factors and processes modulating phenotypes in neuronopathic lysosomal storage diseases.

PubMed

Jakóbkiewicz-Banecka, Joanna; Gabig-Cimińska, Magdalena; Banecka-Majkutewicz, Zyta; Banecki, Bogdan; Węgrzyn, Alicja; Węgrzyn, Grzegorz

2014-03-01

Lysosomal storage diseases are inherited metabolic disorders caused by genetic defects causing deficiency of various lysosomal proteins, and resultant accumulation of non-degraded compounds. They are multisystemic diseases, and in most of them (>70%) severe brain dysfunctions are evident. However, expression of various phenotypes in particular diseases is extremely variable, from non-neuronopathic to severely neurodegenerative in the deficiency of the same enzyme. Although all lysosomal storage diseases are monogenic, clear genotype-phenotype correlations occur only in some cases. In this article, we present an overview on various factors and processes, both general and specific for certain disorders, that can significantly modulate expression of phenotypes in these diseases. On the basis of recent reports describing studies on both animal models and clinical data, we propose a hypothesis that efficiency of production of compounds that cannot be degraded due to enzyme deficiency might be especially important in modulation of phenotypes of patients suffering from lysosomal storage diseases.

CWDPRNP: A tool for cervid prion sequence analysis in program R

USGS Publications Warehouse

Miller, William L.; Walter, W. David

2017-01-01

Chronic wasting disease is a fatal, neurological disease caused by an infectious prion protein, which affects economically and ecologically important members of the family Cervidae. Single nucleotide polymorphisms within the prion protein gene have been linked to differential susceptibility to the disease in many species. Wildlife managers are seeking to determine the frequencies of disease-associated alleles and genotypes and delineate spatial genetic patterns. The CWDPRNP package, implemented in program R, provides a unified framework for analyzing prion protein gene variability and spatial structure.

Comparison of short-term associations with meteorological variables between COPD and pneumonia hospitalization among the elderly in Hong Kong-a time-series study.

PubMed

Lam, Holly Ching-Yu; Chan, Emily Ying-Yang; Goggins, William Bernard

2018-05-05

Pneumonia and chronic obstructive pulmonary diseases (COPD) are the commonest causes of respiratory hospitalization among older adults. Both diseases have been reported to be associated with ambient temperature, but the associations have not been compared between the diseases. Their associations with other meteorological variables have also not been well studied. This study aimed to evaluate the associations between meteorological variables, pneumonia, and COPD hospitalization among adults over 60 and to compare these associations between the diseases. Daily cause-specific hospitalization counts in Hong Kong during 2004-2011 were regressed on daily meteorological variables using distributed lag nonlinear models. Associations were compared between diseases by ratio of relative risks. Analyses were stratified by season and age group (60-74 vs. ≥ 75). In hot season, high temperature (> 28 °C) and high relative humidity (> 82%) were statistically significantly associated with more pneumonia in lagged 0-2 and lagged 0-10 days, respectively. Pneumonia hospitalizations among the elderly (≥ 75) also increased with high solar radiation and high wind speed. During the cold season, consistent hockey-stick associations with temperature and relative humidity were found for both admissions and both age groups. The minimum morbidity temperature and relative humidity were at about 21-22 °C and 82%. The lagged effects of low temperature were comparable for both diseases (lagged 0-20 days). The low-temperature-admissions associations with COPD were stronger and were strongest among the elderly. This study found elevated pneumonia and COPD admissions risks among adults ≥ 60 during periods of extreme weather conditions, and the associations varied by season and age group. Vulnerable groups should be advised to avoid exposures, such as staying indoor and maintaining satisfactory indoor conditions, to minimize risks.

Miscellaneous neurologic or neuromuscular disorders in horses.

PubMed

Aleman, Monica

2011-12-01

NMD is an important cause of morbidity in horses. Signs of dysfunction could be variable depending on the specific area affected. NM disease can go unrecognized if a thorough evaluation is not performed in diseased horses. Electrodiagnostic testing is an area that has the potential to document and improve our understanding of NM disease yet is uncommonly performed. Keeping an open and observant mind will enhance our ability to search and find answers.

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants

PubMed Central

Lenassi, Eva; Vincent, Ajoy; Li, Zheng; Saihan, Zubin; Coffey, Alison J; Steele-Stallard, Heather B; Moore, Anthony T; Steel, Karen P; Luxon, Linda M; Héon, Elise; Bitner-Glindzicz, Maria; Webster, Andrew R

2015-01-01

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration (‘retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one ‘retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype–phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting. PMID:25649381

Assessing the Habitat of Coccidioides posadasii, the Valley Fever Pathogen: A Study of Environmental Variables and Human Incidence Data in Arizona

NASA Astrophysics Data System (ADS)

Mann, Sarina N.

Coccidioidomycosis, or Valley Fever, is an infectious disease caused by inhalation of soil-dwelling fungus Coccidioides posadasii spores in the Lower Sonoran Life Zone (LSLZ) in Arizona. In the context of climate change, the habitat of environmentally-mediated infectious diseases, such as Valley Fever, are expected to change. Connections have been drawn between climate and Valley Fever infection. The operational scale of the organism is still unknown. Here, we use climatic variables, including precipitation, soil moisture, and temperature. We use PRISM precipitation and temperature data, and Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) as a measure of soil moisture for the entire state of Arizona, divided into 126 primary care areas (PCA). These data are analyzed and regressed with Valley Fever incidence to determine the effects of climatic variability on disease distribution and timing. This study confirms that Valley Fever occurrence is clustered in the LSLZ. Seasonal Valley Fever outbreak was found to be variable year-to-year based on climatic variability. The inconclusive regression analyses indicate that the operational scale of Coccidioides is smaller than the PCA region. All variables are related to Valley Fever infection, but one variable was not found to hold more predictive power than others.

Computer-Aided Medical Diagnosis. Literature Review

DTIC Science & Technology

1978-12-15

Croft found a 13% difference in diagnostic accuracy. He considered this difference insignificant in relation to the diagnostic differences caused ...type of diseases diagnosed probably are the major cause of cross-study variability in diagnostic accuracy. The consistency of diagnostic accuracy...REFERENCES ALPEROVITCH, A. and FRAGU, P., A suggestion for an effective use of a computer-aided diagnosis system in screening for hyperthyroidism , Method

Variable intertidal temperature explains why disease endangers black abalone

USGS Publications Warehouse

Ben-Horin, Tal; Lenihan, Hunter S.; Lafferty, Kevin D.

2013-01-01

Epidemiological theory suggests that pathogens will not cause host extinctions because agents of disease should fade out when the host population is driven below a threshold density. Nevertheless, infectious diseases have threatened species with extinction on local scales by maintaining high incidence and the ability to spread efficiently even as host populations decline. Intertidal black abalone (Haliotis cracherodii), but not other abalone species, went extinct locally throughout much of southern California following the emergence of a Rickettsiales-like pathogen in the mid-1980s. The rickettsial disease, a condition known as withering syndrome (WS), and associated mortality occur at elevated water temperatures. We measured abalone body temperatures in the field and experimentally manipulated intertidal environmental conditions in the laboratory, testing the influence of mean temperature and daily temperature variability on key epizootiological processes of WS. Daily temperature variability increased the susceptibility of black abalone to infection, but disease expression occurred only at warm water temperatures and was independent of temperature variability. These results imply that high thermal variation of the marine intertidal zone allows the pathogen to readily infect black abalone, but infected individuals remain asymptomatic until water temperatures periodically exceed thresholds modulating WS. Mass mortalities can therefore occur before pathogen transmission is limited by density-dependent factors.

Identification of Weather Conditions Associated with the Occurrence, Severity, and Incidence of Black Seed Disease of Strawberry Caused by Mycosphaerella fragariae.

PubMed

Carisse, Odile; McNealis, Vanessa

2018-01-01

Black seed disease (BSD) of strawberry is a sporadic disease caused by Mycosphaerella fragariae. Because little is known about potential crop losses or the weather conditions conducive to disease development, fungicides are generally not applied or are applied based on a preset schedule. Data collected from 2000 to 2011 representing 50 farm-years (total of 186 strawberry fields) were used to determine potential crop losses and to study the influence of weather on disease occurrence and development. First, logistic regression was used to model the relationship between occurrence of BSD and weather variables. Second, linear and nonlinear regressions were used to model the number of black seed per berry (severity) and the percentage of diseased berries (incidence). Of the 186 fields monitored, 78 showed black seed symptoms, and the number of black seed per berry ranged from 1 to 10, whereas the percentage of diseased berries ranged from 3 to 32%. The most influential weather variable was total rainfall (in millimeters) in May, with a threshold of 103 mm of rain (absence of BSD < 103 mm < presence of BSD). Similarly, nonlinear models with the total rainfall in May accurately predicted both disease severity and incidence (r = 0.94 and 0.97, respectively). Considering that management actions such as fungicide application are not needed every year in every field, these models could be used to identify fields that are at risk of BSD.

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.

Agro-ecological variations of sheath rot disease of rice caused by Sarocladium oryzae and DNA fingerprinting of the pathogen's population structure.

PubMed

Tajul Islam Chowdhury, M; Salim Mian, M; Taher Mia, M A; Rafii, M Y; Latif, M A

2015-12-28

To examine the impact of regional and seasonal variations on the incidence and severity of sheath rot, a major seed-borne disease of rice caused by Sarocladium oryzae, data on incidence and severity were collected from 27 selected fields in the Gazipur, Rangpur, Bogra, Chittagong, Comilla, Gopalgonj, Jessore, Manikgonj, and Bhola districts of Bangladesh in rain-fed and irrigated conditions. Cultural variability of 29 pathogen isolates obtained from 8 different locations was studied on potato dextrose agar (PDA) and genetic variability was determined by DNA fingerprinting using variable number tandem repeat-polymerase chain reaction markers. Overall, disease incidence and severity were higher in irrigated rice. Disease incidence and severity were highest in the Bhola district in rain-fed rice and lowest in irrigated rice. Mycelial growth of 29 representative isolates was found to vary on PDA and the isolates were divided into 6 groups. The range of the overall size of conidia of the selected isolates was 2.40-7.20 x 1.20-2.40 μm. Analysis of the DNA fingerprint types of the 29 isolates of S. oryzae, obtained from the amplification reactions, revealed 10 fingerprinting types (FPTs) that were 80% similar. FPT-1 was the largest group and included 13 isolates (44.8%), while FPT-2 was the third largest group and included 3 isolates. Each of FPT-3, 4, 5, and 6 included only 1 isolate. We observed no relationship between cultural and genetic groupings.

Heterozygous Germline Mutations in the CBL Tumor-Suppressor Gene Cause a Noonan Syndrome-like Phenotype

PubMed Central

Martinelli, Simone; De Luca, Alessandro; Stellacci, Emilia; Rossi, Cesare; Checquolo, Saula; Lepri, Francesca; Caputo, Viviana; Silvano, Marianna; Buscherini, Francesco; Consoli, Federica; Ferrara, Grazia; Digilio, Maria C.; Cavaliere, Maria L.; van Hagen, Johanna M.; Zampino, Giuseppe; van der Burgt, Ineke; Ferrero, Giovanni B.; Mazzanti, Laura; Screpanti, Isabella; Yntema, Helger G.; Nillesen, Willy M.; Savarirayan, Ravi; Zenker, Martin; Dallapiccola, Bruno; Gelb, Bruce D.; Tartaglia, Marco

2010-01-01

RAS signaling plays a key role in controlling appropriate cell responses to extracellular stimuli and participates in early and late developmental processes. Although enhanced flow through this pathway has been established as a major contributor to oncogenesis, recent discoveries have revealed that aberrant RAS activation causes a group of clinically related developmental disorders characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, ectodermal and musculoskeletal anomalies, and increased risk for certain malignancies. Here, we report that heterozygous germline mutations in CBL, a tumor-suppressor gene that is mutated in myeloid malignancies and encodes a multivalent adaptor protein with E3 ubiquitin ligase activity, can underlie a phenotype with clinical features fitting or partially overlapping Noonan syndrome (NS), the most common condition of this disease family. Independent CBL mutations were identified in two sporadic cases and two families from among 365 unrelated subjects who had NS or suggestive features and were negative for mutations in previously identified disease genes. Phenotypic heterogeneity and variable expressivity were documented. Mutations were missense changes altering evolutionarily conserved residues located in the RING finger domain or the linker connecting this domain to the N-terminal tyrosine kinase binding domain, a known mutational hot spot in myeloid malignancies. Mutations were shown to affect CBL-mediated receptor ubiquitylation and dysregulate signal flow through RAS. These findings document that germline mutations in CBL alter development to cause a clinically variable condition that resembles NS and that possibly predisposes to malignancies. PMID:20619386

Use of canonical variate analysis biplot in examination of choline content data of some foods.

PubMed

Alkan, Baris; Atakan, Cemal

2011-03-01

Adequate intake (AI) of choline as part of the daily diet can help prevent major diseases. Low choline intake is a major risk factor for liver and several neurological disorders. Extreme choline consumption may cause diseases such as hypotension, sweating, diarrhea, and fishy body odor. The AI of choline is 425 mg/day for adult women; higher for pregnant and lactating women. The AI for adult men is 550 mg/day. The total choline content of foods is calculated as the sum of free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine and sphingomyelin. These are called the choline variables. Observed values of choline variables may be different in amounts of nutrients. So different food groups in terms of choline variables are useful to compare. The present paper shows the advantages of using canonical variate analysis biplot to optimally separate groups and explore the differentiality of choline variables amounts in foods.

Dying like rabbits: general determinants of spatio-temporal variability in survival.

PubMed

Tablado, Zulima; Revilla, Eloy; Palomares, Francisco

2012-01-01

1. Identifying general patterns of how and why survival rates vary across space and time is necessary to truly understand population dynamics of a species. However, this is not an easy task given the complexity and interactions of processes involved, and the interpopulation differences in main survival determinants. 2. Here, using European rabbits (Oryctolagus cuniculus) as a model and information from local studies, we investigated whether we could make inferences about trends and drivers of survival of a species that are generalizable to large spatio-temporal scales. To do this, we first focused on overall survival and then examined cause-specific mortalities, mainly predation and diseases, which may lead to those patterns. 3. Our results show that within the large-scale variability in rabbit survival, there exist general patterns that are explained by the integration of factors previously known to be important at the local level (i.e. age, climate, diseases, predation or density dependence). We found that both inter- and intrastudy survival rates increased in magnitude and decreased in variability as rabbits grow old, although this tendency was less pronounced in populations with epidemic diseases. Some causes leading to these higher mortalities in young rabbits could be the stronger effect of rainfall at those ages, as well as, other death sources like malnutrition or infanticide. 4. Predation is also greater for newborns and juveniles, especially in population without diseases. Apart from the effect of diseases, predation patterns also depended on factors, such as, density, season, and type and density of predators. Finally, we observed that infectious diseases also showed general relationships with climate, breeding (i.e. new susceptible rabbits) and age, although the association type varied between myxomatosis and rabbit haemorrhagic disease. 5. In conclusion, large-scale patterns of spatio-temporal variability in rabbit survival emerge from the combination of different factors that interrelate both directly and through density dependence. This highlights the importance of performing more comprehensive studies to reveal combined effects and complex relationships that help us to better understand the mechanisms underlying population dynamics. © 2011 The Authors. Journal of Animal Ecology © 2011 British Ecological Society.

Identifying new diseases and their causes: the dilemma of illnesses in Gulf War veterans.

PubMed

Gardner, John W; Gibbons, Robert V; Hooper, Tomoko I; Cunnion, Stephen O; Kroenke, Kurt; Gackstetter, Gary D

2003-03-01

Since the Gulf War, investigation continues of symptoms and illnesses among its veterans. Yet, identifying a specific "Gulf War Syndrome" remains elusive. With new disease entities, causal associations are relatively easily established when the condition is serious, verifiable, and has excess disease rates in specific groups. In common conditions, many excess cases are required to establish association with a specific exposure. Establishing causality in syndromes with variable symptoms is difficult because specific diagnostic algorithms must be established before causal factors can be properly investigated. Searching for an environmental cause is futile in the absence of an operational disease case definition. Common subjective symptoms (without objective physical or laboratory findings) account for over one-half of all medical outpatient visits, yet these symptoms lack an identified physical cause at least one-third of the time. Our medical care system has difficulty dealing with disorders where there is no identified anatomic abnormality or documented metabolic/physiological dysfunction.

Changes in B cell immunophenotype in common variable immunodeficiency: cause or effect – is bronchiectasis indicative of undiagnosed immunodeficiency?

PubMed Central

Bright, P; Grigoriadou, S; Kamperidis, P; Buckland, M; Hickey, A; Longhurst, H J

2013-01-01

Common variable immunodeficiency (CVID) is the most common severe primary immunodeficiency, but the pathology of this condition is poorly understood. CVID involves a defect in the production of immunoglobulin from B cells, with a subsequent predisposition to infections. Approximately 10–20% of cases are inherited, but even in families with a genetic defect the penetrance is far from complete. A classification system for CVID has been suggested (EUROclass) based on B cell immunophenotyping, but it has not been shown that altered B cell immunophenotype is not a consequence of the complications and treatment of CVID. This study compares the EUROclass B cell immunophenotype of CVID patients (n = 30) with suitable disease controls with bronchiectasis (n = 11), granulomatous disease (Crohn's disease) (n = 9) and neurological patients on immunoglobulin treatment (n = 6). The results of this study correlate with previous literature, that alterations in B cell immunophenotype are associated strongly with CVID. Interestingly, three of the 11 bronchiectasis patients without known immunodeficiency had an altered B cell immunophenotype, suggesting the possibility of undiagnosed immunodeficiency, or that bronchiectasis may cause a secondary alteration in B cell immunophenotype. This study showed a significant difference in B cell immunophenotype between CVID patients compared to disease control groups of granulomatous disease and immunoglobulin treatment. This suggests that granulomatous disease (in Crohn's disease) and immunoglobulin treatment (for chronic neurological conditions) are not causal of an altered B cell immunophenotype in these control populations. PMID:23286946

Spectrum of Clinical Diseases Caused By Disorders of Primary Cilia

PubMed Central

Aygun, Meral Gunay-; Hildebrandt, Friedhelm

2011-01-01

The ciliopathies are a category of diseases caused by disruption of the physiological functions of cilia. Ciliary dysfunction results in a broad range of phenotypes, including renal, hepatic, and pancreatic cyst formation; situs abnormalities; retinal degeneration; anosmia; cerebellar or other brain anomalies; postaxial polydactyly; bronchiectasis; and infertility. The specific clinical features are dictated by the subtype, structure, distribution, and function of the affected cilia. This review highlights the clinical variability caused by dysfunction of motile and nonmotile primary cilia and emphasizes the genetic heterogeneity and phenotypic overlap that are characteristics of these disorders. There is a need for additional research to understand the shared and unique functions of motile and nonmotile cilia and the pathophysiology resulting from mutations in cilia, basal bodies, or centrosomes. Increased understanding of ciliary biology will improve the diagnosis and management of primary ciliary dyskinesia, syndromic ciliopathies, and cilia-related cystic diseases. PMID:21926397

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

Loss-of-function nuclear factor κB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans.

PubMed

Tuijnenburg, Paul; Lango Allen, Hana; Burns, Siobhan O; Greene, Daniel; Jansen, Machiel H; Staples, Emily; Stephens, Jonathan; Carss, Keren J; Biasci, Daniele; Baxendale, Helen; Thomas, Moira; Chandra, Anita; Kiani-Alikhan, Sorena; Longhurst, Hilary J; Seneviratne, Suranjith L; Oksenhendler, Eric; Simeoni, Ilenia; de Bree, Godelieve J; Tool, Anton T J; van Leeuwen, Ester M M; Ebberink, Eduard H T M; Meijer, Alexander B; Tuna, Salih; Whitehorn, Deborah; Brown, Matthew; Turro, Ernest; Thrasher, Adrian J; Smith, Kenneth G C; Thaventhiran, James E; Kuijpers, Taco W

2018-03-02

The genetic cause of primary immunodeficiency disease (PID) carries prognostic information. We conducted a whole-genome sequencing study assessing a large proportion of the NIHR BioResource-Rare Diseases cohort. In the predominantly European study population of principally sporadic unrelated PID cases (n = 846), a novel Bayesian method identified nuclear factor κB subunit 1 (NFKB1) as one of the genes most strongly associated with PID, and the association was explained by 16 novel heterozygous truncating, missense, and gene deletion variants. This accounted for 4% of common variable immunodeficiency (CVID) cases (n = 390) in the cohort. Amino acid substitutions predicted to be pathogenic were assessed by means of analysis of structural protein data. Immunophenotyping, immunoblotting, and ex vivo stimulation of lymphocytes determined the functional effects of these variants. Detailed clinical and pedigree information was collected for genotype-phenotype cosegregation analyses. Both sporadic and familial cases demonstrated evidence of the noninfective complications of CVID, including massive lymphadenopathy (24%), unexplained splenomegaly (48%), and autoimmune disease (48%), features prior studies correlated with worse clinical prognosis. Although partial penetrance of clinical symptoms was noted in certain pedigrees, all carriers have a deficiency in B-lymphocyte differentiation. Detailed assessment of B-lymphocyte numbers, phenotype, and function identifies the presence of an increased CD21 low B-cell population. Combined with identification of the disease-causing variant, this distinguishes between healthy subjects, asymptomatic carriers, and clinically affected cases. We show that heterozygous loss-of-function variants in NFKB1 are the most common known monogenic cause of CVID, which results in a temporally progressive defect in the formation of immunoglobulin-producing B cells. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Neuroinflamm-aging and neurodegenerative diseases: an overview.

PubMed

Pizza, Vincenzo; Agresta, Anella; D'Acunto, Cosimo W; Festa, Michela; Capasso, Anna

2011-08-01

Neuroinflammation is considered a chronic activation of the immune response in the central nervous system (CNS) in response to different injuries. This brain immune activation results in various events: circulating immune cells infiltrate the CNS; resident cells are activated; and pro-inflammatory mediators produced and released induce neuroinflammatory brain disease. The effect of immune diffusible mediators on synaptic plasticity might result in CNS dysfunction during neuroinflammatory brain diseases. The CNS dysfunction may induce several human pathological conditions associated with both cognitive impairment and a variable degree of neuroinflammation. Furthermore, age has a powerful effect on enhanced susceptibility to neurodegenerative diseases and age-dependent enhanced neuroinflammatory processes may play an important role in toxin generation that causes death or dysfunction of neurons in neurodegenerative diseases This review will address current understanding of the relationship between ageing, neuroinflammation and neurodegenerative disease by focusing on the principal mechanisms by which the immune system influences the brain plastic phenomena. Also, the present review considers the principal human neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis and psychiatric disorders caused by aging and neuroinflammation.

Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease.

PubMed

Borgarelli, M; Savarino, P; Crosara, S; Santilli, R A; Chiavegato, D; Poggi, M; Bellino, C; La Rosa, G; Zanatta, R; Haggstrom, J; Tarducci, A

2008-01-01

There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.

An Emerging Tick-Borne Disease of Humans Is Caused by a Subset of Strains with Conserved Genome Structure

PubMed Central

Barbet, Anthony F.; Al-Khedery, Basima; Stuen, Snorre; Granquist, Erik G.; Felsheim, Roderick F.; Munderloh, Ulrike G.

2013-01-01

The prevalence of tick-borne diseases is increasing worldwide. One such emerging disease is human anaplasmosis. The causative organism, Anaplasma phagocytophilum, is known to infect multiple animal species and cause human fatalities in the U.S., Europe and Asia. Although long known to infect ruminants, it is unclear why there are increasing numbers of human infections. We analyzed the genome sequences of strains infecting humans, animals and ticks from diverse geographic locations. Despite extensive variability amongst these strains, those infecting humans had conserved genome structure including the pfam01617 superfamily that encodes the major, neutralization-sensitive, surface antigen. These data provide potential targets to identify human-infective strains and have significance for understanding the selective pressures that lead to emergence of disease in new species. PMID:25437207

The Social Determinants of Chronic Disease

PubMed Central

Cockerham, William C.; Hamby, Bryant W.; Oates, Gabriela R.

2017-01-01

This review article addresses the concept of the social determinants of health (SDH), selected theories, and its application in studies of chronic disease. Once ignored or regarded only as distant or secondary influences on health and disease, social determinants have been increasingly acknowledged as fundamental causes of health afflictions. For the purposes of this discussion, SDH refers to SDH variables directly relevant to chronic diseases and, in some circumstances, obesity, in the research agenda of the Mid-South Transdisciplinary Collaborative Center for Health Disparities Research. The health effects of SDH are initially discussed with respect to smoking and the social gradient in mortality. Next, four leading SDH theories—life course, fundamental cause, social capital, and health lifestyle theory—are reviewed with supporting studies. The article concludes with an examination of neighborhood disadvantage, social networks, and perceived discrimination in SDH research. PMID:27989293

Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis

PubMed Central

Flex, Elisabetta; Jaiswal, Mamta; Pantaleoni, Francesca; Martinelli, Simone; Strullu, Marion; Fansa, Eyad K.; Caye, Aurélie; De Luca, Alessandro; Lepri, Francesca; Dvorsky, Radovan; Pannone, Luca; Paolacci, Stefano; Zhang, Si-Cai; Fodale, Valentina; Bocchinfuso, Gianfranco; Rossi, Cesare; Burkitt-Wright, Emma M.M.; Farrotti, Andrea; Stellacci, Emilia; Cecchetti, Serena; Ferese, Rosangela; Bottero, Lisabianca; Castro, Silvana; Fenneteau, Odile; Brethon, Benoît; Sanchez, Massimo; Roberts, Amy E.; Yntema, Helger G.; Van Der Burgt, Ineke; Cianci, Paola; Bondeson, Marie-Louise; Cristina Digilio, Maria; Zampino, Giuseppe; Kerr, Bronwyn; Aoki, Yoko; Loh, Mignon L.; Palleschi, Antonio; Di Schiavi, Elia; Carè, Alessandra; Selicorni, Angelo; Dallapiccola, Bruno; Cirstea, Ion C.; Stella, Lorenzo; Zenker, Martin; Gelb, Bruce D.; Cavé, Hélène; Ahmadian, Mohammad R.; Tartaglia, Marco

2014-01-01

RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused by constitutional dysregulation of RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS, a gene encoding a small monomeric GTPase controlling cell adhesion, spreading and migration, underlying a rare (2 subjects among 504 individuals analysed) and variable phenotype with features partially overlapping Noonan syndrome, the most common RASopathy. We also identified somatic RRAS mutations (p.Gly39dup and p.Gln87Leu) in 2 of 110 cases of non-syndromic juvenile myelomonocytic leukaemia, a childhood myeloproliferative/myelodysplastic disease caused by upregulated RAS signalling, defining an atypical form of this haematological disorder rapidly progressing to acute myeloid leukaemia. Two of the three identified mutations affected known oncogenic hotspots of RAS genes and conferred variably enhanced RRAS function and stimulus-dependent MAPK activation. Expression of an RRAS mutant homolog in Caenorhabditis elegans enhanced RAS signalling and engendered protruding vulva, a phenotype previously linked to the RASopathy-causing SHOC2S2G mutant. Overall, these findings provide evidence of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease. PMID:24705357

[A regenerative anemia in infants: 2 cases of Pearson´s syndrome].

PubMed

Martínez de Zabarte Fernández, José M; Rodríguez-Vigil Iturrate, Carmen; Martínez Faci, Cristina; García Jiménez, Inmaculada; Murillo Sanjuan, Laura; Muñoz Mellado, Ascensión

2017-02-01

Anemia is very common in infants. Although its causes are usually not severe and treatable, proper etiologic diagnosis should be established. When anemia is non-regenerative, it can be caused by aplastic anemia, myelodysplastic syndrome, bone marrow infiltration or hematopoietic factors deficiencies. Another possible cause is Pearson's syndrome, a rare mitochondrial disease that causes non-regenerative anemia associated with other cytopenias, pancreatic insufficiency, lactic acidosis and great variability in clinical presentation conditioned by heteroplasmy. It is characteristic to find in bone marrow studies variable vacuolization in erythroblastic progenitors and ring sideroblasts. The diagnosis is established by genetic study of mitochondrial deoxyribonucleic acid performed by Southern blot analysis (complete mitochondrial deoxyribonucleic acid amplification by polymerase chain reaction -long), obtaining 70-80% deletion of 4977 bp (NMD 8343-13459). There is no curative therapy and support treatment is the only available nowadays. Death is frequent in early years of life. Sociedad Argentina de Pediatría.

Hispanic-White Differences in Lifespan Variability in the United States

PubMed Central

Lariscy, Joseph T.; Nau, Claudia; Firebaugh, Glenn; Hummer, Robert A.

2016-01-01

This study is the first to investigate whether and, if so, why Hispanics and non-Hispanic whites in the United States differ in the variability of their lifespans. Although Hispanics enjoy higher life expectancy than whites, very little is known about how lifespan variability—and thus uncertainty about length of life—differs by race/ethnicity. We use 2010 U.S. National Vital Statistics System data to calculate lifespan variance at ages 10 and older for Hispanics and whites, and then decompose the Hispanic-white variance difference into cause-specific spread, allocation, and timing effects. In addition to their higher life expectancy relative to whites, Hispanics also exhibit 7 % lower lifespan variability, with a larger gap among women than men. Differences in cause-specific incidence (allocation effects) explain nearly two-thirds of Hispanics’ lower lifespan variability, mainly because of the higher mortality from suicide, accidental poisoning, and lung cancer among whites. Most of the remaining Hispanic-white variance difference is due to greater age dispersion (spread effects) in mortality from heart disease and residual causes among whites than Hispanics. Thus, the Hispanic paradox—that a socioeconomically disadvantaged population (Hispanics) enjoys a mortality advantage over a socioeconomically advantaged population (whites)—pertains to lifespan variability as well as to life expectancy. Efforts to reduce U.S. lifespan variability and simultaneously increase life expectancy, especially for whites, should target premature, young adult causes of death—in particular, suicide, accidental poisoning, and homicide. We conclude by discussing how the analysis of Hispanic-white differences in lifespan variability contributes to our understanding of the Hispanic paradox. PMID:26682740

The Prevalence of Parkinson Disease Among Patients With Hepatitis C Infection.

PubMed

Golabi, Pegah; Otgonsuren, Munkhzul; Sayiner, Mehmet; Arsalla, Aimal; Gogoll, Trevor; Younossi, Zobair M

HCV has been suspected to potentially cause degenerations in the central nervous system. Parkinson's disease is the second most common neurodegenerative disorder. Our aim was to assess the prevalence of Parkinson's disease among patients with HCV infection. For this study, we used Medicare database from 2005-2010. Medicare database contains information on enrollment, coverage, diagnosis recorded with International Classification of Disease, Ninth Revision (ICD-9). From combined inpatient and outpatient files, Parkinson's disease was identified as the first diagnosis by ICD-9 code 332.0. Other study variables were; age, gender, race (White and No White), and Medicare eligibility status. Simple distribution comparison by HCV status examined with t-test for numerical variables and ?2 test for categorical variables in the main analytical cohort as well as in the propensity score matched cohort. A total of 1,236,734 patients (median age 76 years, 41% male, and 85% White) was identified among over 47 million claims. Of these, 6040 patients (0.5%) were infected with HCV. Overall, 0.8% (N = 49) of the HCV group and 1.3% (N = 16,004) of the Non-HCV group had Parkinson's disease (P < 0.001). When the study groups matched for age, gender and race, the prevalence of Parkinson's disease was similar between HCV and Non-HCV groups (P > 0.05). This study revealed that, among Medicare population, HCV was not associated with Parkinson disease.

The association between the supply of primary care physicians and population health outcomes in Korea.

PubMed

Lee, Juhyun; Park, Sangmin; Choi, Kyunghyun; Kwon, Soon-Man

2010-10-01

Several studies reported that primary care improves health outcomes for populations. The objective of this study was to examine the relationship between the supply of primary care physicians and population health outcomes in Korea. Data were extracted from the 2007 report of the Health Insurance Review, the 2005 report from the Korean National Statistical Office, and the 2008 Korean Community Health Survey. The dependent variables were age-adjusted all-cause and disease-specific mortality rates, and independent variables were the supply of primary care physicians, the ratio of primary care physicians to specialists, the number of beds, socioeconomic factors (unemployment rate, local tax, education), population (population size, proportion of the elderly over age 65), and health behaviors (smoking, exercise, using seat belts rates). We used multivariate linear regression as well as ANOVA and t tests. A higher number of primary care physicians was associated with lower all-cause mortality, cancer mortality, and cardiovascular mortality. However, the ratio of primary care physicians to specialists was not related to all-cause mortality. In addition, the relationship between socioeconomic variables and mortality rates was similar in strength to the relationship between the supply of primary care physicians and mortality rates. Accident mortality, suicide mortality, infection mortality, and perinatal mortality were not related to the supply of primary care physicians. The supply of primary care physicians is associated with improved health outcomes, especially in chronic diseases and cancer. However, other variables such as the socioeconomic factors and population factors seem to have a more significant influence on these outcomes.

Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure and mortality: A cohort study

PubMed Central

Muntner, Paul; Whittle, Jeff; Lynch, Amy I.; Colantonio, Lisandro D.; Simpson, Lara M.; Einhorn, Paula T.; Levitan, Emily B.; Whelton, Paul K; Cushman, William C.; Louis, Gail T.; Davis, Barry R.; Oparil, Suzanne

2016-01-01

Background Variability of blood pressure (BP) across outpatient visits is frequently dismissed as random fluctuation around a patient’s underlying BP. Objective: Examine the association between visit-to-visit variability (VVV) of systolic and diastolic BP (SBP and DBP) on cardiovascular disease and mortality outcomes. Design Prospective cohort study Setting Post-hoc analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Participants 25,814 ALLHAT participants. Measurements VVV of SBP was defined as the standard deviation (SD) across BP measurements obtained at 7 visits conducted from 6 to 28 months following ALLHAT enrollment. Participants free of cardiovascular disease events during the first 28 months of follow-up were followed from the month 28 study visit through the end of active ALLHAT follow-up. Outcomes included fatal coronary heart disease or non-fatal myocardial infarction, all-cause mortality, stroke and heart failure. Results There were 1194 cases of fatal CHD or non-fatal MI, 1948 deaths, 606 cases of stroke and 921 cases of heart failure during follow-up. After multivariable adjustment including mean SBP, the hazard ratio comparing participants in the highest versus lowest quintile of SD of SBP (≥14.4 mmHg versus <6.5 mmHg) was 1.30 (1.06–1.59) for fatal coronary heart disease or non-fatal myocardial infarction, 1.58 (1.32–1.90) for all-cause mortality, 1.46 (1.06–2.01) for stroke, and 1.25 (0.97–1.61) for heart failure. Higher VVV of DBP was also associated with cardiovascular disease events and mortality. Limitations Long-term outcomes were not available. Conclusions Higher VVV of SBP is associated with increased cardiovascular disease and mortality risk. Future studies should examine whether reducing VVV of BP lowers this risk. Primary funding source National Institutes of Health PMID:26215765

Social relationships and risk of dementia: a population-based study.

PubMed

Sörman, Daniel Eriksson; Rönnlund, Michael; Sundström, Anna; Adolfsson, Rolf; Nilsson, Lars-Göran

2015-08-01

The objective was to examine whether aspects of social relationships in old age are associated with all-cause dementia and Alzheimer's disease (AD). We studied 1,715 older adults (≥ 65 years) who were dementia-free at baseline over a period of up to 16 years. Data on living status, contact/visit frequency, satisfaction with contact frequency, and having/not having a close friend were analyzed using Cox proportional hazards regressions with all-cause dementia or AD as the dependent variable. To control for reverse causality and to identify potential long-term effects, we additionally performed analyses with delayed entry. We identified 373 incident cases of dementia (207 with AD) during follow-up. The variable visiting/visits from friends was associated with reduced risk of all-cause dementia. Further, a higher value on the relationships index (sum of all variables) was associated with reduced risk of all-cause dementia and AD. However, in analyses with delayed entry, restricted to participants with a survival time of three years or more, none of the social relationship variables was associated with all-cause dementia or AD. The results indicate that certain aspects of social relationships are associated with incident dementia or AD, but also that these associations may reflect reverse causality. Future studies aimed at identifying other factors of a person's social life that may have the potential to postpone dementia should consider the effects of reverse causality.

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...

Phylogenomic and biogeographic reconstruction of the Trichinella complex

USDA-ARS?s Scientific Manuscript database

Trichinellosis is a globally important food-borne parasitic disease of humans. It is caused by roundworms of the Trichinella complex. Extensive biodiversity is reflected in substantial ecological and genetic variability within and among taxa, and major controversy surrounds the systematics of this c...

RELATIONS BETWEEN DAIRY FOOD INTAKE AND ARTERIAL STIFFNESS: PULSE WAVE VELOCITY AND PULSE PRESSURE

PubMed Central

Crichton, Georgina E.; Elias, Merrrill F.; Dore, Gregory A.; Abhayaratna, Walter P.; Robbins, Michael A.

2012-01-01

Modifiable risk factors, such as diet, are becomingly increasingly important in the management of cardiovascular disease, one of the greatest major causes of death and disease burden. Few studies have examined the role of diet as a possible means of reducing arterial stiffness, as measured by pulse wave velocity, an independent predictor of cardiovascular events and all-cause mortality. The aim of this study was to investigate whether dairy food intake is associated with measures of arterial stiffness including carotid-femoral pulse wave velocity and pulse pressure. A cross-sectional analysis of a subset of the Maine Syracuse Longitudinal Study sample was performed. A linear decrease in pulse wave velocity was observed across increasing intakes of dairy food consumption (ranging from never/rarely to daily dairy food intake). The negative linear relationship between pulse wave velocity and intake of dairy food was independent of demographic variables, other cardiovascular disease risk factors and nutrition variables. The pattern of results was very similar for pulse pressure, while no association between dairy food intake and lipid levels was found. Further intervention studies are needed to ascertain whether dairy food intake may be an appropriate dietary intervention for the attenuation of age-related arterial stiffening and reduction of cardiovascular disease risk. PMID:22431583

[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.

Autosomal dominant retinitis pigmentosa with macular involvement associated with a disease haplotype that included a novel PRPH2 variant (p.Cys250Gly).

PubMed

Katagiri, Satoshi; Hayashi, Takaaki; Mizobuchi, Kei; Yoshitake, Kazutoshi; Iwata, Takeshi; Nakano, Tadashi

2018-06-01

It is known that PRPH2 variants appear to be rare causes of retinitis pigmentosa (RP) in the Japanese population. The purpose of this study was to describe clinical and genetic features in autosomal dominant RP (adRP) patients with a novel disease-causing variant in the PRHP2 gene. A total of 57 unrelated Japanese probands with adRP were investigated in this study. Comprehensive ophthalmic examinations include fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography, and electroretinography. Whole exome sequencing or Sanger sequencing for 25 targeted exons of multiple genes causing adRP was performed to identify disease-causing variants. Co-segregation and haplotype analyses were performed to determine a disease-causing gene variant and its haplotype. Genetic analysis identified a novel heterozygous PRPH2 variant (c.748T>G, p.Cys250Gly) as disease causing in four probands from four families. The variant co-segregated with the RP phenotype in the eight affected patients in all families. At least three of the four families shared the same haplotype for the variant allele. Clinically, seven of the eight affected patients exhibited typical RP presentation, as well as variable macular involvement including cystoid macular change, vitelliform-like appearance, choroidal neovascularization, and macular atrophy. The same disease haplotype that included a novel PRPH2 variant (p.Cys250Gly) was identified in three of the four Japanese families with adRP, suggesting a founder effect. Our clinical findings indicate that adRP caused by the p.Cys250Gly variant may accompany macular involvement with high frequency.

Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.

PubMed

Reiterová, Jana; Štekrová, Jitka; Merta, Miroslav; Kotlas, Jaroslav; Elišáková, Veronika; Lněnička, Petr; Korabečná, Marie; Kohoutová, Milada; Tesař, Vladimír

2013-03-15

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background. Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother. We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.

Mycosphaerella comparative genomics reveals chromosome dynamics, genome evolution and stealth pathogenesis

USDA-ARS?s Scientific Manuscript database

Mycosphaerella graminicola causes septoria tritici blotch, one of the most important diseases of wheat worldwide. Previous analyses showed that populations of this species are extremely variable and that polymorphisms for chromosome length and number can be generated during meiosis. To better unders...

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 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.

Pitfalls of mapping a large Turkish consanguineous family with vertical monilethrix inheritance.

PubMed

Celep, F; Uzumcu, A; Sonmez, F M; Uyguner, O; Balci, Y Isik; Bahadir, S; Karaguzel, A

2009-01-01

Monilethrix, a rare autosomal dominant disease characterized by hair fragility and follicular hyperkeratosis, is caused by mutations in three type II hair cortex keratins. The human keratin family comprises 54 members, 28 type I and 26 type II. The phenotype shows variable penetrance and results in hair fragility and patchy dystrophic alopecia. In our study, Monilethrix was diagnosed on the basis of clinical characteristics and microscopic examination in a family with 11 affected members. Haplotype analysis was performed by three Simple Tandem Repeat markers (STR) and KRT86 gene was sequenced for the identification of the disease causing mutation. In the results of this, autosomal dominant mutation (E402K) in exon 7 of KRT86 gene was identified as a cause of Moniltherix in the large family from Turkey.

Mechanisms of Disease and Clinical Features of Mutations of the Gene for Mitofusin 2: An Important Cause of Hereditary Peripheral Neuropathy with Striking Clinical Variability in Children and Adults

ERIC Educational Resources Information Center

Ouvrier, Robert; Grew, Simon

2010-01-01

Mitofusin 2, a large transmembrane GTPase located in the outer mitochondrial membrane, promotes membrane fusion and is involved in the maintenance of the morphology of axonal mitochondria. Mutations of the gene encoding mitofusin 2 ("MFN2") have recently been identified as the cause of approximately one-third of dominantly inherited cases of the…

Retinal vascular changes are a marker for cerebral vascular diseases

PubMed Central

Moss, Heather E.

2016-01-01

The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

Understanding the Hydrology of Cholera in South Asia

NASA Astrophysics Data System (ADS)

Akanda, A. S.; Jutla, A. S.; Islam, S.

2007-12-01

Cholera is an acute waterborne illness caused by the bacterium Vibrio cholerae. The disease remains a major public health issue in several regions of the developing world, mainly in coastal areas around the tropics. Cholera incidences have been historically linked to climate variables and more recently with El Nino-Southern Oscillation. The occurrence of cholera shows bi-annual seasonal peaks and strong inter-annual variability in the Ganges basin region of South Asia. However, the role of hydrologic variables in the seasonal patterns of cholera epidemics is less understood. Preliminary results suggest that a unique combination of increasing water temperature and higher salinity in the coastal zone during the low flow season provide the situation amenable to the first outbreak of cholera in the spring season. Other major factors contributing to the subsequent spread of the disease are sea surface height, monsoon precipitation, and coastal phytoplankton concentration. We will further examine the lag periods between the dominant environmental variables and cholera incidences to understand the seasonal dynamics of cholera in South Asia.

Response of different common bean lines to Phaeoisariopsis griseola in Puerto Rico

USDA-ARS?s Scientific Manuscript database

Angular leaf spot (ALS), caused by Phaeoisariopsis griseola (Sacc.) Ferraris sin. Pseudocercospora griseola (Sacc.) Crous & U. Braun., is an important disease in common bean Phaseolus vulgaris L. in the Caribbean and Central America. The wide pathogen variability makes it necessary to continuously m...

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...

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...

Poliovirus hybrids expressing neutralization epitopes from variable domains I and IV of the major outer membrane protein of Chlamydia trachomatis elicit broadly cross-reactive C. trachomatis-neutralizing antibodies.

PubMed Central

Murdin, A D; Su, H; Klein, M H; Caldwell, H D

1995-01-01

Trachoma and sexually transmitted diseases caused by Chlamydia trachomatis are major health problems worldwide. Epitopes from the variable domains of the major outer membrane protein are candidates for vaccine development. We have constructed hybrid polioviruses expressing sequences from major outer membrane protein variable domains I and IV. Antisera to the hybrids could, in combination, strongly neutralize 8 of the 12 C. trachomatis serovars most commonly associated with oculogenital infections and weakly neutralize the others. PMID:7532625

Rice Sheath Rot: An Emerging Ubiquitous Destructive Disease Complex

PubMed Central

Bigirimana, Vincent de P.; Hua, Gia K. H.; Nyamangyoku, Obedi I.; Höfte, Monica

2015-01-01

Around one century ago, a rice disease characterized mainly by rotting of sheaths was reported in Taiwan. The causal agent was identified as Acrocylindrium oryzae, later known as Sarocladium oryzae. Since then it has become clear that various other organisms can cause similar disease symptoms, including Fusarium sp. and fluorescent pseudomonads. These organisms have in common that they produce a range of phytotoxins that induce necrosis in plants. The same agents also cause grain discoloration, chaffiness, and sterility and are all seed-transmitted. Rice sheath rot disease symptoms are found in all rice-growing areas of the world. The disease is now getting momentum and is considered as an important emerging rice production threat. The disease can lead to variable yield losses, which can be as high as 85%. This review aims at improving our understanding of the disease etiology of rice sheath rot and mainly deals with the three most reported rice sheath rot pathogens: S. oryzae, the Fusarium fujikuroi complex, and Pseudomonas fuscovaginae. Causal agents, pathogenicity determinants, interactions among the various pathogens, epidemiology, geographical distribution, and control options will be discussed. PMID:26697031

Shade tree spatial structure and pod production explain frosty pod rot intensity in cacao agroforests, Costa Rica.

PubMed

Gidoin, Cynthia; Avelino, Jacques; Deheuvels, Olivier; Cilas, Christian; Bieng, Marie Ange Ngo

2014-03-01

Vegetation composition and plant spatial structure affect disease intensity through resource and microclimatic variation effects. The aim of this study was to evaluate the independent effect and relative importance of host composition and plant spatial structure variables in explaining disease intensity at the plot scale. For that purpose, frosty pod rot intensity, a disease caused by Moniliophthora roreri on cacao pods, was monitored in 36 cacao agroforests in Costa Rica in order to assess the vegetation composition and spatial structure variables conducive to the disease. Hierarchical partitioning was used to identify the most causal factors. Firstly, pod production, cacao tree density and shade tree spatial structure had significant independent effects on disease intensity. In our case study, the amount of susceptible tissue was the most relevant host composition variable for explaining disease intensity by resource dilution. Indeed, cacao tree density probably affected disease intensity more by the creation of self-shading rather than by host dilution. Lastly, only regularly distributed forest trees, and not aggregated or randomly distributed forest trees, reduced disease intensity in comparison to plots with a low forest tree density. A regular spatial structure is probably crucial to the creation of moderate and uniform shade as recommended for frosty pod rot management. As pod production is an important service expected from these agroforests, shade tree spatial structure may be a lever for integrated management of frosty pod rot in cacao agroforests.

Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice

PubMed Central

Yamanaka, Koji; Boillee, Severine; Roberts, Elizabeth A.; Garcia, Michael L.; McAlonis-Downes, Melissa; Mikse, Oliver R.; Cleveland, Don W.; Goldstein, Lawrence S. B.

2008-01-01

Dominant mutations in ubiquitously expressed superoxide dismutase (SOD1) cause familial ALS by provoking premature death of adult motor neurons. To test whether mutant damage to cell types beyond motor neurons is required for the onset of motor neuron disease, we generated chimeric mice in which all motor neurons and oligodendrocytes expressed mutant SOD1 at a level sufficient to cause fatal, early-onset motor neuron disease when expressed ubiquitously, but did so in a cellular environment containing variable numbers of non-mutant, non-motor neurons. Despite high-level mutant expression within 100% of motor neurons and oligodendrocytes, in most of these chimeras, the presence of WT non-motor neurons substantially delayed onset of motor neuron degeneration, increasing disease-free life by 50%. Disease onset is therefore non-cell autonomous, and mutant SOD1 damage within cell types other than motor neurons and oligodendrocytes is a central contributor to initiation of motor neuron degeneration. PMID:18492803

Cardiac Channelopathies and Sudden Death: Recent Clinical and Genetic Advances.

PubMed

Fernández-Falgueras, Anna; Sarquella-Brugada, Georgia; Brugada, Josep; Brugada, Ramon; Campuzano, Oscar

2017-01-29

Sudden cardiac death poses a unique challenge to clinicians because it may be the only symptom of an inherited heart condition. Indeed, inherited heart diseases can cause sudden cardiac death in older and younger individuals. Two groups of familial diseases are responsible for sudden cardiac death: cardiomyopathies (mainly hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) and channelopathies (mainly long QT syndrome, Brugada syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). This review focuses on cardiac channelopathies, which are characterized by lethal arrhythmias in the structurally normal heart, incomplete penetrance, and variable expressivity. Arrhythmias in these diseases result from pathogenic variants in genes encoding cardiac ion channels or associated proteins. Due to a lack of gross structural changes in the heart, channelopathies are often considered as potential causes of death in otherwise unexplained forensic autopsies. The asymptomatic nature of channelopathies is cause for concern in family members who may be carrying genetic risk factors, making the identification of these genetic factors of significant clinical importance.

How medicine has become a science?

PubMed

Zieliński, Andrzej

2014-01-01

The historical review of medical activities draws attention how late in its very long history therapies of proven effectiveness were introduced. Author attributes it to the late development of methods which would be capable to determine the causal relations which would scientifically justified identification the causes and risk factors of diseases as well as checking the effectiveness of preventive and therapeutic procedures. Among the fundamental tools for scientific knowledge of the causes and mechanisms of diseases, the author indicates: achievements of basic science and the development of epidemiological methods used to study causal relationships. In the author's opinion the results of basic research are an essential source of variables among which, with an increased likelihood could be found the causes and risk factors of studied conditions, including diseases. The author also stresses the role of medical technology, which is the primary source of potential medicines, other therapeutic procedures and diagnostic methods whose effectiveness is tested in experimental epidemiological studies. Medical technologies create also tools for the development of basic sciences.

Epizootiology of cranial abscess disease in white-tailed deer (Odocoileus virginianus) of Georgia, USA

USGS Publications Warehouse

Cohen, Bradley S.; Belser, Emily H.; Killmaster, Charlie H.; Bowers, John W.; Irwin, Brian J.; Yabsley, Michael J.; Miller, Karl V.

2015-01-01

Intracranial abscess disease is a cause of natural mortality for mature male white-tailed deer (Odocoileus virginianus). Most cases of abscesses are associated with bacterial infection byTrueperella (Arcanobacterium) pyogenes, but a complete understanding of the epidemiology of this disease is lacking. We quantified the effects of individual characteristics, site-specific herd demographics, land cover, and soil variables in estimating the probability of this disease. We examined 7,545 white-tailed deer from 60 sites throughout Georgia US for signs of cranial abscesses, the predecessor of intracranial abscesses, and recorded the presence or absence of cranial abscesses for each individual examined. We detected no cranial abscesses in 2,562 female deer but 91 abscesses in 4,983 male deer examined (1.8%). A generalized linear mixed model, treating site as a random effect, was used to examine several potential explanatory risk factors including site-level landscape and soil characteristics (soil and forest type), demographic factors (deer density and male to female ratio), and individual host factors (deer sex and age). Model results indicated that the probability of a male having a cranial abscess increased with age and that adult sex ratio (male:female) was positively associated with this disease. Site-specific variables for land cover and soil types were not strongly associated with observations of the disease at the scale measured and a large amount of among-site variability remained. Given the demonstrated effect of age, gender, and local sex ratios but the remaining unexplained spatial variability, additional investigation into spatiotemporal variation of the presumed bacterial causative agent of cranial abscesses appears warranted.

Specific and combined subjective responses to noise and their association with cardiovascular diseases.

PubMed

Vandasova, Zdenka; Vencálek, Ondřej; Puklová, Vladimíra

2016-01-01

Noise is one of the most extensive environmental factors affecting the general population. The present study is focused on the association between discomfort caused by noise and the incidence of certain diseases (ischaemic heart disease, stroke and hypertension). This cross-sectional questionnaire study, conducted in 10 cities in the Czech Republic, comprises two stages with 3592 obtained questionnaires in the first phase and 762 in the second phase. Twelve variables describe subjective responses to noise from different sources at different times of day. The intensity of the associations between variables was measured by correlation coefficient. Logistic regression was used for fitting models of morbidity, and confounders such as age and socio-economic status were included. The hypotheses from the first phase were independently validated using data from the second phase. The general rates of noise annoyance/sleep disturbance had greater correlation with traffic noise variables than with neighbourhood noise variables. Factors significantly associated with diseases are: for hypertension - annoyance by traffic noise (the elderly, odds ratio (OR) 1.4) and sleep disturbance by traffic and neighbourhood noise (the elderly, OR 1.6); for ischaemic heart disease - the general rate of noise annoyance (all respondents, OR 1.5 and the adults 30-60 years, OR 1.8) and the general rate of annoyance and sleep disturbance (all respondents, OR 1.3); for stroke - annoyance and sleep disturbance by traffic and neighbourhood noise (all respondents, OR 1.8). Factors that include multiple sources of noise or non-specific noise are associated with the studied diseases more frequently than the source-specific factors.

Four novel connexin 32 mutations in X-linked Charcot-Marie-Tooth disease. Phenotypic variability and central nervous system involvement.

PubMed

Karadima, Georgia; Koutsis, Georgios; Raftopoulou, Maria; Floroskufi, Paraskewi; Karletidi, Karolina-Maria; Panas, Marios

2014-06-15

Charcot-Marie-Tooth (CMT) disease, the most common hereditary neuropathy, is clinically and genetically heterogeneous. X-linked CMT (CMTX) is usually caused by mutations in the gap junction protein b 1 gene (GJB1) coding for connexin 32 (Cx32). The clinical manifestations of CMTX are characterized by significant variability, with some patients exhibiting central nervous system (CNS) involvement. We report four novel mutations in GJB1, c.191G>A (p.Cys64Tyr), c.508G>T (p.Val170Phe), c.778A>G (p.Lys260Glu) and c.300C>G (p.His100Gln) identified in four unrelated Greek families. These mutations were characterized by variable phenotypic expression, including a family with the Roussy-Lévy syndrome, and three of them were associated with mild clinical CNS manifestations. Copyright © 2014. Published by Elsevier B.V.

Effect of production variables on microbiological removal in locally-produced ceramic filters for household water treatment.

PubMed

Lantagne, Daniele; Klarman, Molly; Mayer, Ally; Preston, Kelsey; Napotnik, Julie; Jellison, Kristen

2010-06-01

Diarrhoeal diseases cause an estimated 1.87 million child deaths per year. Point-of-use filtration using locally made ceramic filters improves microbiological quality of stored drinking water and prevents diarrhoeal disease. Scaling-up ceramic filtration is inhibited by lack of universal quality control standards. We investigated filter production variables to determine their affect on microbiological removal during 5-6 weeks of simulated normal use. Decreases in the clay:sawdust ratio and changes in the burnable decreased effectiveness of the filter. Method of silver application and shape of filter did not impact filter effectiveness. A maximum flow rate of 1.7 l(-hr) was established as a potential quality control measure for one particular filter to ensure 99% (2- log(10)) removal of total coliforms. Further research is indicated to determine additional production variables associated with filter effectiveness and develop standardized filter production procedures prior to scaling-up.

Common Variable Immunodeficiency Caused by FANC Mutations.

PubMed

Sekinaka, Yujin; Mitsuiki, Noriko; Imai, Kohsuke; Yabe, Miharu; Yabe, Hiromasa; Mitsui-Sekinaka, Kanako; Honma, Kenichi; Takagi, Masatoshi; Arai, Ayako; Yoshida, Kenichi; Okuno, Yusuke; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Miyano, Satoru; Muramatsu, Hideki; Kojima, Seiji; Hira, Asuka; Takata, Minoru; Ohara, Osamu; Ogawa, Seishi; Morio, Tomohiro; Nonoyama, Shigeaki

2017-07-01

Common variable immunodeficiency (CVID) is the most common adult-onset primary antibody deficiency disease due to various causative genes. Several genes, which are known to be the cause of different diseases, have recently been reported as the cause of CVID in patients by performing whole exome sequencing (WES) analysis. Here, we found FANC gene mutations as a cause of adult-onset CVID in two patients. B cells were absent and CD4 + T cells were skewed toward CD45RO + memory T cells. T-cell receptor excision circles (TRECs) and signal joint kappa-deleting recombination excision circles (sjKRECs) were undetectable in both patients. Both patients had no anemia, neutropenia, or thrombocytopenia. Using WES, we identified compound heterozygous mutations of FANCE in one patient and homozygous mutation of FANCA in another patient. The impaired function of FANC protein complex was confirmed by a monoubiquitination assay and by chromosome fragility test. We then performed several immunological evaluations including quantitative lymphocyte analysis and TRECs/sjKRECs analysis for 32 individuals with Fanconi anemia (FA). In total, 22 FA patients (68.8%) were found to have immunological abnormalities, suggesting that such immunological findings may be common in FA patients. These data indicate that FANC mutations are involved in impaired lymphogenesis probably by the accumulation of DNA replication stress, leading to CVID. It is important to diagnose FA because it drastically changes clinical management. We propose that FANC mutations can cause isolated immunodeficiency in addition to bone marrow failure and malignancy.

Variability of Late-Night Salivary Cortisol in Cushing Disease: A Prospective Study.

PubMed

Sandouk, Zahrae; Johnston, Philip; Bunch, Dustin; Wang, Sihe; Bena, James; Hamrahian, Amir; Kennedy, Laurence

2018-03-01

The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear. To assess the frequency of variable hormonogenesis in patients presenting with CD. Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights. Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal. Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.

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...

Natural Burkholderia mallei Infection in Dromedary, Bahrain

PubMed Central

Wernery, Ulrich; Wernery, Renate; Joseph, Marina; Al-Salloom, Fajer; Johnson, Bobby; Kinne, Joerg; Jose, Shanti; Jose, Sherry; Tappendorf, Britta; Hornstra, Heidie

2011-01-01

We confirm a natural infection of dromedaries with glanders. Multilocus variable number tandem repeat analysis of a Burkholderia mallei strain isolated from a diseased dromedary in Bahrain revealed close genetic proximity to strain Dubai 7, which caused an outbreak of glanders in horses in the United Arab Emirates in 2004. PMID:21762586

Unexpected Genome Variability at Multiple Loci Suggests Cacao Swollen Shoot Virus Comprises Multiple, Divergent Molecular Variants.

USDA-ARS?s Scientific Manuscript database

Cacao swollen shoot virus (CSSV) [Badnavirus, Caulimoviridae] causes swollen shoot disease of Theobroma cacao L. in West Africa. Since ~2000, various diagnostic tests have failed to detect CSSV in ~50-70% of symptomatic cacao plants, suggesting the possible emergence of new, previously uncharacteriz...

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...

Natural Burkholderia mallei infection in Dromedary, Bahrain.

PubMed

Wernery, Ulrich; Wernery, Renate; Joseph, Marina; Al-Salloom, Fajer; Johnson, Bobby; Kinne, Joerg; Jose, Shanti; Jose, Sherry; Tappendorf, Britta; Hornstra, Heidie; Scholz, Holger C

2011-07-01

We confirm a natural infection of dromedaries with glanders. Multilocus variable number tandem repeat analysis of a Burkholderia mallei strain isolated from a diseased dromedary in Bahrain revealed close genetic proximity to strain Dubai 7, which caused an outbreak of glanders in horses in the United Arab Emirates in 2004.

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...

Health and Household Air Pollution from Solid Fuel Use: The Needfor Improved Exposure Assessment

EPA Science Inventory

Background: Nearly half the world’s population relies on solid fuel combustion to meet basic household energy needs (e.g., cooking and heating). Resulting air pollution exposures are estimated to cause 3% of the global burden of disease. Large variability and a lack of resource...

Progression of Mortality due to Diseases of the Circulatory System and Human Development Index in Rio de Janeiro Municipalities

PubMed Central

Soares, Gabriel Porto; Klein, Carlos Henrique; Silva, Nelson Albuquerque de Souza e; de Oliveira, Glaucia Maria Moraes

2016-01-01

Background Diseases of the circulatory system (DCS) are the major cause of death in Brazil and worldwide. Objective To correlate the compensated and adjusted mortality rates due to DCS in the Rio de Janeiro State municipalities between 1979 and 2010 with the Human Development Index (HDI) from 1970 onwards. Methods Population and death data were obtained in DATASUS/MS database. Mortality rates due to ischemic heart diseases (IHD), cerebrovascular diseases (CBVD) and DCS adjusted by using the direct method and compensated for ill-defined causes. The HDI data were obtained at the Brazilian Institute of Applied Research in Economics. The mortality rates and HDI values were correlated by estimating Pearson linear coefficients. The correlation coefficients between the mortality rates of census years 1991, 2000 and 2010 and HDI data of census years 1970, 1980 and 1991 were calculated with discrepancy of two demographic censuses. The linear regression coefficients were estimated with disease as the dependent variable and HDI as the independent variable. Results In recent decades, there was a reduction in mortality due to DCS in all Rio de Janeiro State municipalities, mainly because of the decline in mortality due to CBVD, which was preceded by an elevation in HDI. There was a strong correlation between the socioeconomic indicator and mortality rates. Conclusion The HDI progression showed a strong correlation with the decline in mortality due to DCS, signaling to the relevance of improvements in life conditions. PMID:27849263

Progression of Mortality due to Diseases of the Circulatory System and Human Development Index in Rio de Janeiro Municipalities.

PubMed

Soares, Gabriel Porto; Klein, Carlos Henrique; Silva, Nelson Albuquerque de Souza E; Oliveira, Glaucia Maria Moraes de

2016-10-01

Diseases of the circulatory system (DCS) are the major cause of death in Brazil and worldwide. To correlate the compensated and adjusted mortality rates due to DCS in the Rio de Janeiro State municipalities between 1979 and 2010 with the Human Development Index (HDI) from 1970 onwards. Population and death data were obtained in DATASUS/MS database. Mortality rates due to ischemic heart diseases (IHD), cerebrovascular diseases (CBVD) and DCS adjusted by using the direct method and compensated for ill-defined causes. The HDI data were obtained at the Brazilian Institute of Applied Research in Economics. The mortality rates and HDI values were correlated by estimating Pearson linear coefficients. The correlation coefficients between the mortality rates of census years 1991, 2000 and 2010 and HDI data of census years 1970, 1980 and 1991 were calculated with discrepancy of two demographic censuses. The linear regression coefficients were estimated with disease as the dependent variable and HDI as the independent variable. In recent decades, there was a reduction in mortality due to DCS in all Rio de Janeiro State municipalities, mainly because of the decline in mortality due to CBVD, which was preceded by an elevation in HDI. There was a strong correlation between the socioeconomic indicator and mortality rates. The HDI progression showed a strong correlation with the decline in mortality due to DCS, signaling to the relevance of improvements in life conditions.

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.

Spatial and temporal variation in emergency transport during periods of extreme heat in Japan: A nationwide study.

PubMed

Onozuka, Daisuke; Hagihara, Akihito

2016-02-15

Several studies have reported the burden of climate change on extreme heat-related mortality or morbidity. However, few studies have investigated the spatial and temporal variation in emergency transport during periods of extreme heat on a national scale. Daily emergency ambulance dispatch data from 2007 to 2010 were acquired from all 47 prefectures of Japan. The temporal variability in the relationship between heat and morbidity in each prefecture was estimated using Poisson regression combined with a distributed lag non-linear model and adjusted for time trends. The spatial variability in the heat-morbidity relationships between prefectures was estimated using a multivariate meta-analysis. A total of 5,289,660 emergency transports were reported during the summer months (June through September) within the study period. The overall cumulative relative risk (RR) at the 99th percentile vs. the minimum morbidity percentile was 1.292 (95% CI: 1.251-1.333) for all causes, 1.039 (95% CI: 0.989-1.091) for cardiovascular diseases, and 1.287 (95% CI: 1.210-1.368) for respiratory diseases. Temporal variation in the estimated effects indicated a non-linear relationship, and there were differences in the temporal variations between heat and all-cause and cause-specific morbidity. Spatial variation between prefectures was observed for all causes (Cochran Q test, p<0.001; I(2)=45.8%); however, there was no significant spatial heterogeneity for cardiovascular (Cochran Q test, p=0.054; I(2)=15.1%) and respiratory (Cochran Q test, p=0.681; I(2)=1.0%) diseases. Our nationwide study demonstrated differences in the spatial and temporal variations in the relative risk for all-cause and cause-specific emergency transport during periods of extreme heat in Japan between 2007 and 2010. Our results suggest that public health strategies aimed at controlling heat-related morbidity should be tailored according to region-specific weather conditions. Copyright © 2015 Elsevier B.V. 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

A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without Hirschsprung disease.

PubMed

Sznajer, Yves; Coldéa, Cristina; Meire, Françoise; Delpierre, Isabelle; Sekhara, Tayeb; Touraine, Renaud L

2008-04-15

Type 4 Waardenburg syndrome represents a well define entity caused by neural crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central, autonomous and peripheral nervous systems) leading, with variable expressivity, to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when Sox10 gene mutation is identified. We report the natural history of a child who presented with synophrys, vivid blue eye, deafness, bilateral complete semicircular canals agenesis with mental retardation, subtle signs for peripheral neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype findings underline the wide spectrum of SOX10 gene implication in unusual type 4 Waardenburg syndrome patient. Copyright 2008 Wiley-Liss, Inc.

Prognostic factors for survival in patients with Ewing's sarcoma using the surveillance, epidemiology, and end results (SEER) program database.

PubMed

Duchman, Kyle R; Gao, Yubo; Miller, Benjamin J

2015-04-01

The current study aims to determine cause-specific survival in patients with Ewing's sarcoma while reporting clinical risk factors for survival. The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify patients with osseous Ewing's sarcoma from 1991 to 2010. Patient, tumor, and socioeconomic variables were analyzed to determine prognostic factors for survival. There were 1163 patients with Ewing's sarcoma identified in the SEER Program database. The 10-year cause-specific survival for patients with non-metastatic disease at diagnosis was 66.8% and 28.1% for patients with metastatic disease. Black patients demonstrated reduced survival at 10 years with an increased frequency of metastatic disease at diagnosis as compared to patients of other race, while Hispanic patients more frequently presented with tumor size>10cm. Univariate analysis revealed that metastatic disease at presentation, tumor size>10cm, axial tumor location, patient age≥20 years, black race, and male sex were associated with decreased cause-specific survival at 10 years. Metastatic disease at presentation, axial tumor location, tumor size>10cm, and age≥20 years remained significant in the multivariate analysis. Patients with Ewing's sarcoma have decreased cause-specific survival at 10 years when metastatic at presentation, axial tumor location, tumor size>10cm, and patient age≥20 years. Copyright © 2015 Elsevier Ltd. All rights reserved.

Shift work and overall and cause-specific mortality in the Danish nurse cohort.

PubMed

Jørgensen, Jeanette Therming; Karlsen, Sashia; Stayner, Leslie; Andersen, Johnni; Andersen, Zorana Jovanovic

2017-03-01

Objectives Evidence of an effect of shift work on all-cause and cause-specific mortality is inconsistent. This study aims to examine whether shift work is associated with increased all-cause and cause-specific mortality. Methods We linked 28 731 female nurses (age ≥44 years), recruited in 1993 or 1999 from the Danish nurse cohort where they reported information on shift work (night, evening, rotating, or day), to the Danish Register of Causes of Death to identify deaths up to 2013. We used Cox regression models with age as the underlying scale to examine the associations between night, evening, and rotating shift work (compared to day shift work) and all-cause and cause-specific mortality in models adjusted for potentially confounding variables. Results Of 18 015 nurses included in this study, 1616 died during the study time period from the following causes: cardiovascular disease (N=217), cancer (N= 945), diabetes (N=20), Alzheimer's disease or dementia (N=33), and psychiatric diseases (N=67). We found that working night [hazard ratio (HR) 1.26, 95% confidence interval 95% CI) 1.05-1.51] or evening (HR 1.29, 95% CI 1.11-1.49) shifts was associated with a significant increase in all-cause mortality when compared to working day shift. We found a significant association of night shift work with cardiovascular disease (HR 1.71, 95% CI 1.09-2.69) and diabetes (HR 12.0, 95% CI 3.17-45.2, based on 8 cases) and none with overall cancer mortality (HR 1.05, 95% CI 0.81-1.35) or mortality from psychiatric diseases (HR 1.17, 95% CI 0.47-2.92). Finally, we found strong association between evening (HR 4.28, 95% CI 1.62-11.3) and rotating (HR 5.39, 95% CI 2.35-12.3) shift work and mortality from Alzheimer's disease and dementia (based on 8 and 14 deaths among evening and rotating shift workers, respectively). Conclusions Women working night and evening shifts have increased all-cause, cardiovascular, diabetes, and Alzheimer's and dementia mortality.

Insights on adaptive and innate immunity in canine leishmaniosis.

PubMed

Hosein, Shazia; Blake, Damer P; Solano-Gallego, Laia

2017-01-01

Canine leishmaniosis (CanL) is caused by the parasite Leishmania infantum and is a systemic disease, which can present with variable clinical signs, and clinicopathological abnormalities. Clinical manifestations can range from subclinical infection to very severe systemic disease. Leishmaniosis is categorized as a neglected tropical disease and the complex immune responses associated with Leishmania species makes therapeutic treatments and vaccine development challenging for both dogs and humans. In this review, we summarize innate and adaptive immune responses associated with L. infantum infection in dogs, and we discuss the problems associated with the disease as well as potential solutions and the future direction of required research to help control the parasite.

Molecular Investigation of Tularemia Outbreaks, Spain, 1997–2008

PubMed Central

Ariza-Miguel, Jaime; Johansson, Anders; Fernández-Natal, María Isabel; Martínez-Nistal, Carmen; Orduña, Antonio; Rodríguez-Ferri, Elías F.; Hernández, Marta

2014-01-01

Tularemia outbreaks occurred in northwestern Spain in 1997–1998 and 2007–2008 and affected >1,000 persons. We assessed isolates involved in these outbreaks by using pulsed-field gel electrophoresis with 2 restriction enzymes and multilocus variable number tandem repeat analysis of 16 genomic loci of Francisella tularensis, the cause of this disease. Isolates were divided into 3 pulsotypes by pulsed-field gel electrophoresis and 8 allelic profiles by multilocus variable number tandem repeat analysis. Isolates obtained from the second tularemia outbreak had the same genotypes as isolates obtained from the first outbreak. Both outbreaks were caused by genotypes of genetic subclade B.Br:FTNF002–00, which is widely distributed in countries in central and western Europe. Thus, reemergence of tularemia in Spain was not caused by the reintroduction of exotic strains, but probably by persistence of local reservoirs of infection. PMID:24750848

Cardiovascular disease in spinal cord injury: an overview of prevalence, risk, evaluation, and management.

PubMed

Myers, Jonathan; Lee, Matthew; Kiratli, Jenny

2007-02-01

Cardiovascular disease is a growing concern for the spinal cord-injured (SCI) population. For long-term SCI, morbidity and mortality from cardiovascular causes now exceeds that caused by renal and pulmonary conditions, the primary causes of mortality in previous decades. Although risk estimates commonly used for ambulatory individuals have not been established from follow-up studies in SCI, nearly all risk factors tend to be more prevalent in SCI subjects compared with ambulatory subjects. These risks include a greater prevalence of obesity, lipid disorders, metabolic syndrome, and diabetes. Daily energy expenditure is significantly lower in SCI individuals, not only because of a lack of motor function, but also because of a lack of accessibility and fewer opportunities to engage in physical activity. Autonomic dysfunction caused by SCI is also associated with several conditions that contribute to heightened cardiovascular risk, including abnormalities in blood pressure, heart rate variability, arrhythmias, and a blunted cardiovascular response to exercise that can limit the capacity to perform physical activity. Thus, screening, recognition, and treatment of cardiovascular disease should be an essential component of managing individuals with SCI, and judicious treatment of risk factors can play an important role in minimizing the incidence of cardiovascular disease in these individuals. This article reviews the cardiovascular consequences of chronic SCI, including the prevalence of cardiovascular disease and risk factors unique to these individuals, and provides a synopsis of management of cardiovascular disease in this population.

Update on the therapy of Behçet disease

PubMed Central

Saleh, Zeinab

2014-01-01

Behçet disease is a chronic inflammatory systemic disorder, characterized by a relapsing and remitting course. It manifests with oral and genital ulcerations, skin lesions, uveitis, and vascular, central nervous system and gastrointestinal involvement. The main histopathological finding is a widespread vasculitis of the arteries and veins of any size. The cause of this disease is presumed to be multifactorial involving infectious triggers, genetic predisposition, and dysregulation of the immune system. As the clinical expression of Behçet disease is heterogeneous, pharmacological therapy is variable and depends largely on the severity of the disease and organ involvement. Treatment of Behçet disease continues to be based largely on anecdotal case reports, case series, and a few randomized clinical trials. PMID:24790727

Seasonal temperature is associated with Parkinson's disease prescriptions: an ecological study

NASA Astrophysics Data System (ADS)

Rowell, David; Nghiem, Son; Ramagopalan, Sreeram; Meier, Ute-Christiane

2017-12-01

The aim of this study is to test what effect the weather may have on medications prescribed to treat Parkinson's disease. Twenty-three years of monthly time, series data was sourced from the Pharmaceutical Benefits Scheme (PBS) and the Bureau of Meteorology (BOM). Data were available for eight states and territories and their corresponding capital cities. The dependent variable was the aggregate levodopa equivalent dose (LED) for 51 Parkinson's medications identified on the PBS. Two explanatory variables of interest, temperature and solar exposure, were identified in the BOM data set. Linear and cosinor models were estimated with fixed and random effects, respectively. The prescribed LED was 4.2% greater in January and 4.5% lower in July. Statistical analysis showed that temperature was associated with the prescription of Parkinson medications. Our results suggest seasonality exists in Parkinson's disease symptoms and this may be related to temperature. Further work is needed to confirm these findings and understand the underlying mechanisms as a better understanding of the causes of any seasonal variation in Parkinson's disease may help clinicians and patients manage the disease more effectively.

Analysis of underlying causes of inter-expert disagreement in retinopathy of prematurity diagnosis. Application of machine learning principles.

PubMed

Ataer-Cansizoglu, E; Kalpathy-Cramer, J; You, S; Keck, K; Erdogmus, D; Chiang, M F

2015-01-01

Inter-expert variability in image-based clinical diagnosis has been demonstrated in many diseases including retinopathy of prematurity (ROP), which is a disease affecting low birth weight infants and is a major cause of childhood blindness. In order to better understand the underlying causes of variability among experts, we propose a method to quantify the variability of expert decisions and analyze the relationship between expert diagnoses and features computed from the images. Identification of these features is relevant for development of computer-based decision support systems and educational systems in ROP, and these methods may be applicable to other diseases where inter-expert variability is observed. The experiments were carried out on a dataset of 34 retinal images, each with diagnoses provided independently by 22 experts. Analysis was performed using concepts of Mutual Information (MI) and Kernel Density Estimation. A large set of structural features (a total of 66) were extracted from retinal images. Feature selection was utilized to identify the most important features that correlated to actual clinical decisions by the 22 study experts. The best three features for each observer were selected by an exhaustive search on all possible feature subsets and considering joint MI as a relevance criterion. We also compared our results with the results of Cohen's Kappa [36] as an inter-rater reliability measure. The results demonstrate that a group of observers (17 among 22) decide consistently with each other. Mean and second central moment of arteriolar tortuosity is among the reasons of disagreement between this group and the rest of the observers, meaning that the group of experts consider amount of tortuosity as well as the variation of tortuosity in the image. Given a set of image-based features, the proposed analysis method can identify critical image-based features that lead to expert agreement and disagreement in diagnosis of ROP. Although tree-based features and various statistics such as central moment are not popular in the literature, our results suggest that they are important for diagnosis.

Revisiting the Evolution of Mycobacterium bovis

PubMed Central

Mostowy, Serge; Inwald, Jackie; Gordon, Steve; Martin, Carlos; Warren, Rob; Kremer, Kristin; Cousins, Debby; Behr, Marcel A.

2005-01-01

Though careful consideration has been placed towards genetic characterization of tubercle bacillus isolates causing disease in humans, those causing disease predominantly among wild and domesticated mammals have received less attention. In contrast to Mycobacterium tuberculosis, whose host range is largely specific to humans, M. bovis and “M bovis-like” organisms infect a broad range of animal species beyond their most prominent host in cattle. To determine whether strains of variable genomic content are associated with distinct distributions of disease, the DNA contents of M. bovis or M. bovis-like isolates from a variety of hosts were investigated via Affymetrix GeneChip. Consistent with previous genomic analysis of the M. tuberculosis complex (MTC), large sequence polymorphisms of putative diagnostic and biological consequence were able to unambiguously distinguish interrogated isolates. The distribution of deleted regions indicates organisms genomically removed from M. bovis and also points to structured genomic variability within M. bovis. Certain genomic profiles spanned a variety of hosts but were clustered by geography, while others associated primarily with host type. In contrast to the prevailing assumption that M. bovis has broad host capacity, genomic profiles suggest that distinct MTC lineages differentially infect a variety of mammals. From this, a phylogenetic stratification of genotypes offers a predictive framework upon which to base future genetic and phenotypic studies of the MTC. PMID:16159772

Legg-Calvé-Perthes disease in a child with osteopetrosis

PubMed Central

Sims, Alex L.; Barwick, Thomas W.; Montgomery, Richard J.

2011-01-01

Osteopetrosis is a rare inherited disorder of bone causing increased bone density. Legg-Calvé-Perthes disease (LCPD), by contrast, is a more common idiopathic condition leading to variable avascular necrosis of the immature femoral head. We present a case of a 5-year-old boy presenting with these co-morbidities. We have found only one previous reference suggesting these two conditions can coexist in the literature. We discuss the basic principles of management of this interesting case. PMID:24765380

Disseminated melioidosis presenting as septic arthritis.

PubMed

Rajadhyaksha, Anjali; Sonawale, Archana; Khare, Shruti; Kalal, Chetan; Jankar, Rahul

2012-06-01

Melioidosis is an infection caused by Burkholderia pseudomallei. The disease is known as a remarkable imitator due to the wide and variable clinical spectrum of its manifestations. Septic arthritis is rare but well-recognized manifestation of this disease. We report a case of melioidosis in a 52 year male with uncontrolled diabetes mellitus (DM) presenting with a rare combination of septic arthritis and abscesses in the chest wall, liver and subcutaneous tissue. The patient responded to prolonged treatment of intravenous ceftazidime followed by oral co-trimoxazole.

Enhancing Subjective Well-Being in Individuals with Asthma

ERIC Educational Resources Information Center

Bray, Melissa A.; Kehle, Thomas J.; Peck, Heather L.; Theodore, Lea A.; Zhou, Zheng

2004-01-01

Asthma, a chronic respiratory disease, is caused by a complex interaction between genetic and environmental variables. The intent of this article is to propose a theory that provides an explanation for the reduction of emotionally triggered asthma through treatments derived from positive psychology. The basic tenet of the theory is that physical…

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...

Use of quantitative traits to assess aggressiveness of Phakopsora pachyrhizi isolates from Nigeria and the United States

USDA-ARS?s Scientific Manuscript database

Soybean rust, caused by Phakopsora pachyrhizi, is one of the most important foliar diseases of soybean worldwide. The soybean-P. pachyrhizi interaction is often complex because of the genetic variability in host and pathogen genotypes. In a compatible reaction, soybean genotypes produce tan colored ...

Extreme intrafamilial variability of Saudi brothers with primary hyperoxaluria type 1

PubMed Central

Alfadhel, Majid; Alhasan, Khalid A; Alotaibi, Mohammed; Al Fakeeh, Khalid

2012-01-01

Background 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. Case report 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. Conclusion Clinicians should be aware of extreme intrafamilial variability of PH1 and international registries are needed to characterize the genotype-phenotype correlation in such disorder. PMID:22956877

[Molecular aspects of the antiviral response against hepatitis C virus implicated in vaccines development].

PubMed

Llanes, María Soledad; Palacios, Natalia Soledad; Piccione, Magalí; Ruiz, María Guillermina; Layana, Carla

2015-04-01

Hepatitis C is a contagious liver disease caused by hepacivirus of the Flaviviridae family. It has a RNA genome, a unique highly variable molecule. It encodes ten proteins which are necessary to infect cells and multiply. Replication occurs only in hepatocytes. Because of its wide genomic variability and the absence of symptoms, it is difficult to make an early diagnosis and successful treatment. In this review we analyze the molecular mechanism by which the virus infects the hepatocytes and causes the disease. We focused the analysis on different therapies, with the possibility of improving treatment with the use of new specific vaccines. We highlight the use of new therapies based on nucleic acids, mainly DNA vectors. In the near future, once this treatment is adequately evaluated in clinical trials, and the costs are calculated, it could be a very beneficial alternative to conventional methods. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Influence of disease on population model of mid-continent mallards

USGS Publications Warehouse

Samuel, Michael D.

1992-01-01

On numerous occasions, waterfowl deaths caused by disease were highly visible to wildlife managers and to the general public. Thousands of birds died during duck plague, avian botulism and avian cholera outbreaks. Undoubtedly, some disease occurred in waterfowl populations throughout their evolution; however, knowledge of disease epizootiology primarily developed during the past 40-50 years (Wobeser 1981) for diseases that cause massive die-offs (e.g., avian cholera, avian botulism and duck plague). Other diseases, such as avian tuberculosis, aspergillosis, parasite infection and lead poisoning, also occur at chronic levels, but the data remain meager on many of these less spectacular causes of mortality and sublethal forms of disease. However, because chronic losses occur throughout the year, their cumulative effect, as well as the large die-offs, are a potential threat to waterfowl populations (Bellrose 1976, Wobeser 1981). Previous studies (Anderson 1975) demonstrated that 50 percent of the annual mortality in mallard (Anas platyrhynchos) populations is from nonhunting causes. In addition to disease, these causes include predation, accidental deaths, inclement weather and other factors (Stout and Cornwell 1976), which can be confounded by disease. Determination of mortality rates from diseases has been difficult because many biases and inconsistencies are associated with the available data. Assessment of disease prevalence and magnitude of losses is complicated by the spatial and temporal variability of many diseases, the logistic difficulty of studying highly mobile waterfowl populations, and the potentially confounding influences of predation and scavenging on detecting disease-related mortality;. Unless losses are so extensive that they direct attention to a particular area, mortality from disease is easily overlooked (see Zwank et al. 1985). Even when die-offs are evident, mortality from disease may be underestimated because sick waterfowl become debilitated, seek seclusion in dense cover and are removed by efficient predators or scavengers prior to human detection. Our objective was to evaluate the possible effects of three of the most common diseases (friend 1985), avian cholera, avian botulism and lead poisoning, on the population dynamics of mid-continental mallards. We used data from disease outbreaks to develop preliminary estimates of mortality rates and their temporal pattern. A computer model was used to integrate these mortality estimate with other mallard life history characteristics, evaluate the potential effects of these diseases on mallard demographics and assess the need for better information on the effects of disease on mallards.

Unexpected Abscess Localization of the Anterior Abdominal Wall in an ADPKD Patient Undergoing Hemodialysis.

PubMed

Sabanis, Nikos; Paschou, Eleni; Gavriilaki, Eleni; Mourounoglou, Maria; Vasileiou, Sotirios

2015-01-01

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common monogenic disorders and the leading inheritable cause of end-stage renal disease worldwide. Cystic and noncystic extrarenal manifestations are correlated with variable clinical presentations so that an inherited disorder is now considered a systemic disease. Kidney and liver cystic infections are the most common infectious complications in ADPKD patients. Furthermore, it is well known that ADPKD is commonly associated with colonic diverticular disease which recently has been reported to be linked to increased risk of infection on hemodialysis patients. Herein, we present a case of anterior abdominal wall abscess caused by Enterococcus faecalis in a patient with ADPKD undergoing hemodialysis. Although the precise pathway of infection remains uncertain, the previous medical history as well as the clinical course of our patient led us to hypothesize an alternative route of infection from the gastrointestinal tract through an aberrant intestinal barrier into the bloodstream and eventually to an atypical location.

Partners in crime: bidirectional transcription in unstable microsatellite disease.

PubMed

Batra, Ranjan; Charizanis, Konstantinos; Swanson, Maurice S

2010-04-15

Nearly two decades have passed since the discovery that the expansion of microsatellite trinucleotide repeats is responsible for a prominent class of neurological disorders, including Huntington disease and fragile X syndrome. These hereditary diseases are characterized by genetic anticipation or the intergenerational increase in disease severity accompanied by a decrease in age-of-onset. The revelation that the variable expansion of simple sequence repeats accounted for anticipation spawned a number of pathogenesis models and a flurry of studies designed to reveal the molecular events affected by these expansions. This work led to our current understanding that expansions in protein-coding regions result in extended homopolymeric amino acid tracts, often polyglutamine or polyQ, and deleterious protein gain-of-function effects. In contrast, expansions in noncoding regions cause RNA-mediated toxicity. However, the realization that the transcriptome is considerably more complex than previously imagined, as well as the emerging regulatory importance of antisense RNAs, has blurred this distinction. In this review, we summarize evidence for bidirectional transcription of microsatellite disease genes and discuss recent suggestions that some repeat expansions produce variable levels of both toxic RNAs and proteins that influence cell viability, disease penetrance and pathological severity.

Preimplantation genetic diagnosis for cystic fibrosis: a case report.

PubMed

Biazotti, Maria Cristina Santoro; Pinto Junior, Walter; Albuquerque, Maria Cecília Romano Maciel de; Fujihara, Litsuko Shimabukuro; Suganuma, Cláudia Haru; Reigota, Renata Bednar; Bertuzzo, Carmen Sílvia

2015-01-01

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This disorder produces a variable phenotype including lung disease, pancreatic insufficiency, and meconium ileus plus bilateral agenesis of the vas deferens causing obstructive azoospermia and male infertility. Preimplantation genetic diagnosis is an alternative that allows identification of embryos affected by this or other genetic diseases. We report a case of couple with cystic fibrosis; the woman had the I148 T mutation and the man had the Delta F508 gene mutation. The couple underwent in vitro fertilization, associated with preimplantation genetic diagnosis, and with subsequent selection of healthy embryos for uterine transfer. The result was an uneventful pregnancy and delivery of a healthy male baby.

Preimplantation genetic diagnosis for cystic fibrosis: a case report

PubMed Central

Biazotti, Maria Cristina Santoro; Pinto, Walter; de Albuquerque, Maria Cecília Romano Maciel; Fujihara, Litsuko Shimabukuro; Suganuma, Cláudia Haru; Reigota, Renata Bednar; Bertuzzo, Carmen Sílvia

2015-01-01

Cystic fibrosis is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This disorder produces a variable phenotype including lung disease, pancreatic insufficiency, and meconium ileus plus bilateral agenesis of the vas deferens causing obstructive azoospermia and male infertility. Preimplantation genetic diagnosis is an alternative that allows identification of embryos affected by this or other genetic diseases. We report a case of couple with cystic fibrosis; the woman had the I148 T mutation and the man had the Delta F508 gene mutation. The couple underwent in vitro fertilization, associated with preimplantation genetic diagnosis, and with subsequent selection of healthy embryos for uterine transfer. The result was an uneventful pregnancy and delivery of a healthy male baby. PMID:25993078

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.

Environmental Attributes to Respiratory Diseases of Small Ruminants

PubMed Central

Rahal, Anu; Ahmad, Abul Hasan; Prakash, Atul; Mandil, Rajesh; Kumar, Aruna T.

2014-01-01

Respiratory diseases are the major disease crisis in small ruminants. A number of pathogenic microorganisms have been implicated in the development of respiratory disease but the importance of environmental factors in the initiation and progress of disease can never be overemphasized. They irritate the respiratory tree producing stress in the microenvironment causing a decline in the immune status of the small ruminants and thereby assisting bacterial, viral, and parasitic infections to break down the tissue defense barriers. Environmental pollutants cause acute or chronic reactions as they deposit on the alveolar surface which are characterized by inflammation or fibrosis and the formation of transitory or persistent tissue manifestation. Some of the effects of exposures may be immediate, whereas others may not be evident for many decades. Although the disease development can be portrayed as three sets of two-way communications (pathogen-environment, host-environment, and host-pathogen), the interactions are highly variable. Moreover, the environmental scenario is never static; new compounds are introduced daily making a precise evaluation of the disease burden almost impossible. The present review presents a detailed overview of these interactions and the ultimate effect on the respiratory health of sheep and goat. PMID:24782941

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.

The short-term association of road traffic noise with cardiovascular, respiratory, and diabetes-related mortality.

PubMed

Recio, Alberto; Linares, Cristina; Banegas, José R; Díaz, Julio

2016-10-01

Road traffic noise has well-documented effects on cardiovascular, respiratory, and metabolic health. Numerous studies have reported long-term associations of urban noise with some diseases and outcomes, including death. However, to date there are no studies on the short-term association between this pollutant and a set of various specific causes of death. To investigate the short-term association of road traffic noise with daily cause-specific mortality. We used a time-stratified case-crossover design with Poisson regression. Predictor variables were daytime, nighttime, and 24-h equivalent noise levels, and maximum daytime and nighttime noise levels. Outcome variables were daily death counts for various specific causes, stratifying by age. We adjusted for primary air pollutants (PM2.5 and NO2) and weather conditions (mean temperature and relative humidity). In the ≥65 age group, increased mortality rates per 1 dBA increase in maximum nocturnal noise levels at lag 0 or 1 day were 2.9% (95% CI 1.0, 4.8%), 3.5% (95% CI 1.1, 6.1%), 2.4% (95% CI 0.1, 4.8%), 3.0% (95% CI 0.2, 5.8%), and 4.0% (95% CI 1.0, 7.0%), for ischemic heart disease, myocardial infarction, cerebrovascular disease, pneumonia, and COPD, respectively. For diabetes, 1 dBA increase in equivalent nocturnal noise levels at lag 1 was associated with an increased mortality rate of 11% (95% CI 4.0, 19%). In the <65 age group, increased mortality rates per 1 dBA increase in equivalent nocturnal noise levels at lag 0 were 11% (95% CI 4.2, 18%) and 11% (95% CI 4.2, 19%) for ischemic heart disease and myocardial infarction, respectively. Road traffic noise increases the short-term risk of death from specific diseases of the cardiovascular, respiratory, and metabolic systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Direct inpatient burden caused by foot-related conditions: a multisite point-prevalence study

PubMed Central

Lazzarini, Peter A; Hurn, Sheree E; Kuys, Suzanne S; Kamp, Maarten C; Ng, Vanessa; Thomas, Courtney; Jen, Scott; Kinnear, Ewan M; d'Emden, Michael C; Reed, Lloyd

2016-01-01

Objective The aims of this point-prevalence study were to investigate a representative inpatient population to determine the prevalence of people admitted to hospital for the reason of a foot-related condition, and identify associated independent factors. Methods Participants were adult inpatients in 5 different representative hospitals, admitted for any reason on the day of data collection. Maternity, mental health and cognitively impaired inpatients were excluded. Participants were surveyed on a range of self-reported demographic, social determinant, medical history, foot disease history, self-care, footwear, past foot treatment prior to hospitalisation and reason for admission variables. Physical examinations were performed to clinically diagnose a range of foot disease and foot risk factor variables. Independent factors associated with being admitted to hospital for the primary or secondary reason of a foot-related condition were analysed using multivariate logistic regression. Results Overall, 733 participants were included; mean (SD) age 62 (19) years, male 55.8%. Foot-related conditions were the primary reason for admission in 54 participants (7.4% (95% CI 5.7% to 9.5%)); 36 for foot disease (4.9%), 15 foot trauma (2.1%). Being admitted for the primary reason of a foot-related condition was independently associated with foot infection, critical peripheral arterial disease, foot trauma and past foot treatment by a general practitioner and surgeon (p<0.01). Foot-related conditions were a secondary reason for admission in 28 participants (3.8% (2.6% to 5.6%)), and were independently associated with diabetes and current foot ulcer (p<0.01). Conclusions This study, the first in a representative inpatient population, suggests the direct inpatient burden caused by foot-related conditions is significantly higher than previously appreciated. Findings indicate 1 in every 13 inpatients was primarily admitted because of a foot-related condition with most due to foot disease or foot trauma. Future strategies are recommended to investigate and intervene in the considerable inpatient burden caused by foot-related conditions. PMID:27324710

Prognostic value of the oxygen uptake efficiency slope and other exercise variables in patients with coronary artery disease.

PubMed

Coeckelberghs, Ellen; Buys, Roselien; Goetschalckx, Kaatje; Cornelissen, Véronique A; Vanhees, Luc

2016-02-01

Peak exercise capacity is an independent predictor for mortality in patients with coronary artery disease. However, sometimes cardiopulmonary exercise tests are stopped prematurely. Therefore, submaximal exercise measures such as the oxygen uptake efficiency slope have been introduced. The aim of this study was to assess the prognostic value of the oxygen uptake efficiency slope and other exercise parameters, in patients with coronary artery disease. Between 2000 and 2011, 1409 patients with coronary artery disease (age 60.7 ± 9.9 years; 1205 males) underwent cardiopulmonary exercise tests. A maximal effort was not reached in 161 (11.5%) patients. The oxygen uptake efficiency slope was calculated and information on mortality was obtained. Cox proportional hazards regression analyses were used to assess the relation of oxygen uptake efficiency slope and other gas exchange variables with all-cause and cardiovascular mortality. Receiver operating characteristic curve analyses was performed to define optimal cut-off values. During an average follow-up of 7.45 ± 3.20 years (range 0.16-13.95 years), 158 patients died, among which 68 patients for cardiovascular reasons. The oxygen uptake efficiency slope was related to all-cause (hazard ratio: 0.568, p < 0.001) and cardiovascular (hazard ratio: 0.461, p < 0.001) mortality. When significant covariates were entered in the analysis, oxygen uptake efficiency slope remained related to mortality (p < 0.05). When other submaximal exercise parameters were added to the model, oxygen uptake efficiency slope and minute ventilation/carbon dioxide production slope also remained significantly related to mortality. The oxygen uptake efficiency slope is an independent predictor for all-cause and cardiovascular mortality in patients with coronary artery disease, irrespective of a truly maximal effort during cardiopulmonary exercise tests. Furthermore, the oxygen uptake efficiency slope provides prognostic information, complementary to the minute ventilation/carbon dioxide production slope and peak exercise capacity. © The European Society of Cardiology 2015.

Variability of Powassan virus cultured in tissue explants and organism of Hyalomma anatolicum ticks.

PubMed

Khozinskaya, G A; Chunikhin, S P; Khozinsky, V V; Stefutkina, L F

1985-07-01

The variability of Powassan virus was studied during successive passages in Hyalomma anatolicum ticks or prolonged reproduction in their tissue explants. It had been shown that in the course of tick passages and during reproduction in the explants, pathogenicity of the virus in respect to causing acute disease in mice after peripheral inoculation was decreased, while virus ability to cause death after intracerebral (i.c.) inoculation remained unchanged. In mice infected with the original strain P-40 of Powassan virus damaging effect of the immune response prevailed, while in mice infected with the strains passaged for a long time in ticks (strain P-40Hat) or in tick tissue explants (strain P-40Haex), the protective effect of the immune response was prominent.

[Prevention and control of air pollution needs to strengthen further study on health damage caused by air pollution].

PubMed

Wu, T C

2016-08-06

Heath issues caused by air pollution such as particulate matter (PM) are much concerned and focused among air, water and soil pollutions because human breathe air for whole life span. Present comments will review physical and chemical characteristics of PM2.5 and PM10; Dose-response associations of PM10, PM2.5 and their components with mortality and risk of cardiopulmonary diseases, early health damages such as the decrease of lung functions and heart rate variability, DNA damage; And the roles of genetic variations and epigenetic changes in lung functions and heart rate variability, DNA damage related to PMs and their components. This comments list some limitations and perspectives about the associations of air pollution with health.

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

Multisystemic Disease Modeling of Liver-Derived Protein Folding Disorders Using Induced Pluripotent Stem Cells (iPSCs).

PubMed

Leung, Amy; Murphy, George J

2016-01-01

Familial transthyretin amyloidosis (ATTR) is an autosomal dominant protein-folding disorder caused by over 100 distinct mutations in the transthyretin (TTR) gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. Here, we describe detailed methodologies for the directed differentiation of protein folding disease-specific iPSCs into hepatocytes that produce mutant protein, and neural-lineage cells often targeted in disease. Methodologies are also described for the construction of multisystem models and drug screening using iPSCs.

Posttreatment Lyme disease syndrome.

PubMed

Aucott, John N

2015-06-01

The prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause termed posttreatment Lyme disease syndrome (PTLDS), characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy. Risk factors include delayed diagnosis, increased severity of symptoms, and presence of neurologic symptoms at time of initial treatment. Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease. Optimal treatment of PTLDS awaits more precise understanding of the pathophysiologic mechanisms involved in this illness and future treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Complete genome sequence of a new enamovirus from Argentina infecting alfalfa plants showing dwarfism symptoms.

PubMed

Bejerman, Nicolás; Giolitti, Fabián; Trucco, Verónica; de Breuil, Soledad; Dietzgen, Ralf G; Lenardon, Sergio

2016-07-01

Alfalfa dwarf disease, probably caused by synergistic interactions of mixed virus infections, is a major and emergent disease that threatens alfalfa production in Argentina. Deep sequencing of diseased alfalfa plant samples from the central region of Argentina resulted in the identification of a new virus genome resembling enamoviruses in sequence and genome structure. Phylogenetic analysis suggests that it is a new member of the genus Enamovirus, family Luteoviridae. The virus is tentatively named "alfalfa enamovirus 1" (AEV-1). The availability of the AEV-1 genome sequence will make it possible to assess the genetic variability of this virus and to construct an infectious clone to investigate its role in alfalfa dwarfism disease.

Clinical manifestations and management of Gaucher disease.

PubMed

Linari, Silvia; Castaman, Giancarlo

2015-01-01

Gaucher disease is a rare multi-systemic metabolic disorder caused by the inherited deficiency of the lysosomal enzyme β-glucocerebrosidase, which leads to the accumulation of its normal substrate, glucocerebroside, in tissue macrophages with damage to haematological, visceral and bone systems. Anaemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of the most prevalent form of the disease, the so-called non-neuronopathic type 1. However, severity and coexistence of different symptoms are highly variable. The determination of deficient β-glucocerebrosidase activity in leukocytes or fibroblasts by enzymatic assay is the gold standard for the diagnosis of Gaucher disease. Comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects are fundamental for the effective management of Gaucher disease patients. Enzyme replacement therapy has been shown to be effective in reducing glucocerebroside storage burden and diminishing the deleterious effects caused by its accumulation. Tailored treatment plan for each patient should be directed to symptom relief, general improvement of quality of life, and prevention of irreversible damage.

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.

Herbal hepatotoxicity: suspected cases assessed for alternative causes.

PubMed

Teschke, Rolf; Schulze, Johannes; Schwarzenboeck, Alexander; Eickhoff, Axel; Frenzel, Christian

2013-09-01

Alternative explanations are common in suspected drug-induced liver injury (DILI) and account for up to 47.1% of analyzed cases. This raised the question of whether a similar frequency may prevail in cases of assumed herb-induced liver injury (HILI). We searched the Medline database for the following terms: herbs, herbal drugs, herbal dietary supplements, hepatotoxic herbs, herbal hepatotoxicity, and herb-induced liver injury. Additional terms specifically addressed single herbs and herbal products: black cohosh, Greater Celandine, green tea, Herbalife products, Hydroxycut, kava, and Pelargonium sidoides. We retrieved 23 published case series and regulatory assessments related to hepatotoxicity by herbs and herbal dietary supplements with alternative causes. The 23 publications comprised 573 cases of initially suspected HILI; alternative causes were evident in 278/573 cases (48.5%). Among them were hepatitis by various viruses (9.7%), autoimmune diseases (10.4%), nonalcoholic and alcoholic liver diseases (5.4%), liver injury by comedication (DILI and other HILI) (43.9%), and liver involvement in infectious diseases (4.7%). Biliary and pancreatic diseases were frequent alternative diagnoses (11.5%), raising therapeutic problems if specific treatment is withheld; pre-existing liver diseases including cirrhosis (9.7%) were additional confounding variables. Other diagnoses were rare, but possibly relevant for the individual patient. In 573 cases of initially assumed HILI, 48.5% showed alternative causes unrelated to the initially incriminated herb, herbal drug, or herbal dietary supplement, calling for thorough clinical evaluations and appropriate causality assessments in future cases of suspected HILI.

Personalized Medicine for Chronic Respiratory Infectious Diseases: Tuberculosis, Nontuberculous Mycobacterial Pulmonary Diseases, and Chronic Pulmonary Aspergillosis.

PubMed

Salzer, Helmut J F; Wassilew, Nasstasja; Köhler, Niklas; Olaru, Ioana D; Günther, Gunar; Herzmann, Christian; Kalsdorf, Barbara; Sanchez-Carballo, Patricia; Terhalle, Elena; Rolling, Thierry; Lange, Christoph; Heyckendorf, Jan

2016-01-01

Chronic respiratory infectious diseases are causing high rates of morbidity and mortality worldwide. Tuberculosis, a major cause of chronic pulmonary infection, is currently responsible for approximately 1.5 million deaths per year. Although important advances in the fight against tuberculosis have been made, the progress towards eradication of this disease is being challenged by the dramatic increase in multidrug-resistant bacilli. Nontuberculous mycobacteria causing pulmonary disease and chronic pulmonary aspergillosis are emerging infectious diseases. In contrast to other infectious diseases, chronic respiratory infections share the trait of having highly variable treatment outcomes despite longstanding antimicrobial therapy. Recent scientific progress indicates that medicine is presently at a transition stage from programmatic to personalized management. We explain current state-of-the-art management concepts of chronic pulmonary infectious diseases as well as the underlying methods for therapeutic decisions and their implications for personalized medicine. Furthermore, we describe promising biomarkers and techniques with the potential to serve future individual treatment concepts in this field of difficult-to-treat patients. These include candidate markers to improve individual risk assessment for disease development, the design of tailor-made drug therapy regimens, and individualized biomarker-guided therapy duration to achieve relapse-free cure. In addition, the use of therapeutic drug monitoring to reach optimal drug dosing with the smallest rate of adverse events as well as candidate agents for future host-directed therapies are described. Taken together, personalized medicine will provide opportunities to substantially improve the management and treatment outcome of difficult-to-treat patients with chronic respiratory infections. © 2016 S. Karger AG, Basel.

Optimism and Cause-Specific Mortality: A Prospective Cohort Study

PubMed Central

Kim, Eric S.; Hagan, Kaitlin A.; Grodstein, Francine; DeMeo, Dawn L.; De Vivo, Immaculata; Kubzansky, Laura D.

2017-01-01

Growing evidence has linked positive psychological attributes like optimism to a lower risk of poor health outcomes, especially cardiovascular disease. It has been demonstrated in randomized trials that optimism can be learned. If associations between optimism and broader health outcomes are established, it may lead to novel interventions that improve public health and longevity. In the present study, we evaluated the association between optimism and cause-specific mortality in women after considering the role of potential confounding (sociodemographic characteristics, depression) and intermediary (health behaviors, health conditions) variables. We used prospective data from the Nurses’ Health Study (n = 70,021). Dispositional optimism was measured in 2004; all-cause and cause-specific mortality rates were assessed from 2006 to 2012. Using Cox proportional hazard models, we found that a higher degree of optimism was associated with a lower mortality risk. After adjustment for sociodemographic confounders, compared with women in the lowest quartile of optimism, women in the highest quartile had a hazard ratio of 0.71 (95% confidence interval: 0.66, 0.76) for all-cause mortality. Adding health behaviors, health conditions, and depression attenuated but did not eliminate the associations (hazard ratio = 0.91, 95% confidence interval: 0.85, 0.97). Associations were maintained for various causes of death, including cancer, heart disease, stroke, respiratory disease, and infection. Given that optimism was associated with numerous causes of mortality, it may provide a valuable target for new research on strategies to improve health. PMID:27927621

Trends in cause specific mortality across occupations in Japanese men of working age during period of economic stagnation, 1980-2005: retrospective cohort study.

PubMed

Wada, Koji; Kondo, Naoki; Gilmour, Stuart; Ichida, Yukinobu; Fujino, Yoshihisa; Satoh, Toshihiko; Shibuya, Kenji

2012-03-06

To assess the temporal trends in occupation specific all causes and cause specific mortality in Japan between 1980 and 2005. Longitudinal analysis of individual death certificates by last occupation before death. Data on population by age and occupation were derived from the population census. Government records, Japan. Men aged 30-59. Age standardised mortality rate for all causes, all cancers, cerebrovascular disease, ischaemic heart disease, unintentional injuries, and suicide. Age standardised mortality rates for all causes and for the four leading causes of death (cancers, ischaemic heart disease, cerebrovascular disease, and unintentional injuries) steadily decreased from 1980 to 2005 among all occupations except for management and professional workers, for whom rates began to rise in the late 1990s (P<0.001). During the study period, the mortality rate was lowest in other occupations such as production/labour, clerical, and sales workers, although overall variability of the age standardised mortality rate across occupations widened. The rate for suicide rapidly increased since the late 1990s, with the greatest increase being among management and professional workers. Occupational patterns in cause specific mortality changed dramatically in Japan during the period of its economic stagnation and resulted in the reversal of occupational patterns in mortality that have been well established in western countries. A significant negative effect on the health of management and professional workers rather than clerks and blue collar workers could be because of increased job demands and more stressful work environments and could have eliminated or even reversed the health inequality across occupations that had existed previously.

Registry of the Spanish Network for Systemic Sclerosis

PubMed Central

Simeón-Aznar, C.P.; Fonollosa-Plá, V.; Tolosa-Vilella, Carles; Espinosa-Garriga, G.; Campillo-Grau, M.; Ramos-Casals, M.; García-Hernández, F.J.; Castillo-Palma, M.J.; Sánchez-Román, J.; Callejas-Rubio, J.L.; Ortego-Centeno, N.; Egurbide-Arberas, M.V.; Trapiellla-Martínez, L.; Caminal-Montero, L.; Sáez-Comet, L.; Velilla-Marco, J.; Camps-García, M.T.; de Ramón-Garrido, E.; Esteban-Marcos, E.M.; Pallarés-Ferreres, L.; Navarrete-Navarrete, N.; Vargas-Hitos, J.A.; de la Torre, R. Gómez; Salvador-Cervello, G.; Rios-Blanco, J.J.; Vilardell-Tarrés, M.

2015-01-01

Abstract Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan–Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors. PMID:26512564

Assessment of Normal Variability in Peripheral Blood Gene Expression

DOE PAGES

Campbell, Catherine; Vernon, Suzanne D.; Karem, Kevin L.; ...

2002-01-01

Peripheral blood is representative of many systemic processes and is an ideal sample for expression profiling of diseases that have no known or accessible lesion. Peripheral blood is a complex mixture of cell types and some differences in peripheral blood gene expression may reflect the timing of sample collection rather than an underlying disease process. For this reason, it is important to assess study design factors that may cause variability in gene expression not related to what is being analyzed. Variation in the gene expression of circulating peripheral blood mononuclear cells (PBMCs) from three healthy volunteers sampled three times onemore » day each week for one month was examined for 1,176 genes printed on filter arrays. Less than 1% of the genes showed any variation in expression that was related to the time of collection, and none of the changes were noted in more than one individual. These results suggest that observed variation was due to experimental variability.« less

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.

Antigenic variability: Obstacles on the road to vaccines against traditionally difficult targets.

PubMed

Servín-Blanco, R; Zamora-Alvarado, R; Gevorkian, G; Manoutcharian, K

2016-10-02

Despite the impressive impact of vaccines on public health, the success of vaccines targeting many important pathogens and cancers has to date been limited. The burden of infectious diseases today is mainly caused by antigenically variable pathogens (AVPs), which escape immune responses induced by prior infection or vaccination through changes in molecular structures recognized by antibodies or T cells. Extensive genetic and antigenic variability is the major obstacle for the development of new or improved vaccines against "difficult" targets. Alternative, qualitatively new approaches leading to the generation of disease- and patient-specific vaccine immunogens that incorporate complex permanently changing epitope landscapes of intended targets accompanied by appropriate immunomodulators are urgently needed. In this review, we highlight some of the most critical common issues related to the development of vaccines against many pathogens and cancers that escape protective immune responses owing to antigenic variation, and discuss recent efforts to overcome the obstacles by applying alternative approaches for the rational design of new types of immunogens.

Molecular typing of Chinese Streptococcus pyogenes isolates.

PubMed

You, Yuanhai; Wang, Haibin; Bi, Zhenwang; Walker, Mark; Peng, Xianhui; Hu, Bin; Zhou, Haijian; Song, Yanyan; Tao, Xiaoxia; Kou, Zengqiang; Meng, Fanliang; Zhang, Menghan; Bi, Zhenqiang; Luo, Fengji; Zhang, Jianzhong

2015-06-01

Streptococcus pyogenes causes human infections ranging from mild pharyngitis and impetigo to serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. The objective of this study was to compare molecular emm typing and pulsed field gel electrophoresis (PFGE) with multiple-locus variable-number tandem-repeat analysis (MLVA) for genotyping of Chinese S. pyogenes isolates. Molecular emm typing and PFGE were performed using standard protocols. Seven variable number tandem repeat (VNTR) loci reported in a previous study were used to genotype 169 S. pyogenes geographically-diverse isolates from China isolated from a variety of disease syndromes. Multiple-locus variable-number tandem-repeat analysis provided greater discrimination between isolates when compared to emm typing and PFGE. Removal of a single VNTR locus (Spy2) reduced the sensitivity by only 0.7%, which suggests that Spy2 was not informative for the isolates screened. The results presented support the use of MLVA as a powerful epidemiological tool for genotyping S. pyogenes clinical isolates. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identifying Plants of Stampede Pinto Bean with Resistance to New races of Rust Pathogen

USDA-ARS?s Scientific Manuscript database

The rust disease of dry beans is caused by a hyper-variable fungus that continually produces new virulent strains. Two new strains, known as races, emerged in Michigan and North Dakota in 2007 and 2008, respectively, which surmounted the resistance of a widely used rust-resistance gene known as Ur-...

Pathogenic variability of individuals and populations of cucurbit powdery mildew–great confusion and great mystery, or why we still need the classical phytopathology.

USDA-ARS?s Scientific Manuscript database

Golovinomyces cichoracearum and Podosphaera xanthii (family Erysiphales) are considered the most important species causing cucurbit powdery mildew (CPM), a serious disease of field and greenhouse cucurbits. Podosphaera xanthii (Px) is common in subtropical and tropical areas and in greenhouses in te...

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 ...

Pathogenicity, fungicide resistance, and genetic variability of Phytophthora rubi isolates from raspberry (Rubus idaeus) in the Western United States

USDA-ARS?s Scientific Manuscript database

Root rot of raspberry (Rubus idaeus), thought to be primarily caused by Phytophthora rubi, is an economically important disease in the western United States. The objectives of this study were to determine which Phytophthora species are involved in root rot, examine the efficacy of different isolatio...

Initial characterization of unidentified Armillaria isolate from Serbia using LSU-IGS1 and TEF-1a genes

Treesearch

N. Keca; N. B. Klopfenstein; M.-S. Kim; H. Solheim; S. Woodward

2014-01-01

Armillaria species have a global distribution and play variable ecological roles, including causing root disease of diverse forest, ornamental and horticultural trees. Accurate identification of Armillaria species is critical to understand their distribution and ecological roles. This work focused on characterizing an unidentified Armillaria isolate from a Serbian...

Canopy decline assessment in American elm after inoculation with different doses of Ophiostoma ulmi and O. novo-ulmi

Treesearch

Charles E. Flower; James M. Slavicek; Dale Lesser; Steven Eshita; Cornelia C. Pinchot

2017-01-01

Restoration of American elm (Ulmus americana L.) in natural and urban landscapes necessitates the development of new selections that not only exhibit Dutch elm disease (DED, caused by the fungal pathogen Ophiostoma novo-ulmi and O. ulmi) tolerance, but also an increase the genetic variability of tolerant...

Genomic selection for BCWD resistance in Rainbow trout using RADSNP and SNP genotyping platforms, single-step GBLUP and Bayesian variable selection models

USDA-ARS?s Scientific Manuscript database

Bacterial cold water disease (BCWD) causes significant economic losses in salmonid aquaculture. At the National Center for Cool and Cold Water Aquaculture (NCCCWA), we have pursued selective breeding to increase rainbow trout genetic resistance against BCWD and found that post-challenge survival is ...

Delayed-enhanced cardiac MRI for differentiation of Fabry's disease from symmetric hypertrophic cardiomyopathy.

PubMed

De Cobelli, Francesco; Esposito, Antonio; Belloni, Elena; Pieroni, Maurizio; Perseghin, Gianluca; Chimenti, Cristina; Frustaci, Andrea; Del Maschio, Alessandro

2009-03-01

Fabry's disease may be difficult to differentiate from symmetric hypertrophic cardiomyopathy. Our aim was to compare the myocardial location and distribution patterns of delayed enhancement between patients with Fabry's disease who are affected by symmetric myocardial hypertrophy and patients with symmetric hypertrophic cardiomyopathy in order to identify a specific sign to best differentiate the two diseases. Patients with Fabry's disease-related hypertrophy showed left ventricular (LV) delayed enhancement with a typical and consistently found pattern characterized by the involvement of the inferolateral basal or mid basal segments and a mesocardial distribution that spared the subendocardium. This pattern seems to be specific to Fabry's disease; in fact, patients with symmetric hypertrophic cardiomyopathy had variable locations and distributions of delayed enhancement. These observations may contribute to identifying Fabry's disease as a specific cause of symmetric hypertrophy.

Dog Ownership and Mortality in England: A Pooled Analysis of Six Population-based Cohorts.

PubMed

Ding, Ding; Bauman, Adrian E; Sherrington, Cathie; McGreevy, Paul D; Edwards, Kate M; Stamatakis, Emmanuel

2018-02-01

Dog ownership may be associated with reduced risk for cardiovascular disease. However, data are scant on the relationship between dog ownership and all-cause and cause-specific mortality risk. Data from six separate cohorts (1995-1997, 2001-2002, 2004) of the Health Survey for England were pooled and analyzed in 2017. Participants were 59,352 adults (mean age 46.5, SD=17.9 years) who consented to be linked to the National Death Registry. Living in a household with a dog was reported at baseline. Outcomes included all-cause and cardiovascular disease mortality (determined using ICD-9 codes 390-459, ICD-10 codes I01-I99). Multilevel Weibull survival analysis was used to examine the associations between dog ownership and mortality, adjusted for various sociodemographic and lifestyle variables. Potential effect modifiers, including age, sex, education, living circumstances, longstanding illness, and prior diagnosis of cardiovascular disease, were also examined. During 679,441 person-years of follow-up (mean 11.5, SD=3.8 years), 8,169 participants died from all causes and 2,451 from cardiovascular disease. In the fully adjusted models, there was no statistically significant association between dog ownership and mortality outcomes (hazard ratio=1.03, 95% CI=0.98, 1.09, for all-cause mortality; and hazard ratio=1.07, 95% CI=0.96, 1.18, for cardiovascular disease mortality) and no significant effect modification. There is no evidence for an association between living in a household with a dog and all-cause or cardiovascular disease mortality in this large sample. These results should be interpreted in light of limitations in the measurement of dog ownership and its complexity in potential long-term health implications. Future studies should measure specific aspects of ownership, such as caring responsibilities and temporality. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

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.

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.

Causes of death among people living with AIDS in the pre- and post-HAART Eras in the city of São Paulo, Brazil.

PubMed

Domingues, Carmen-Silvia Bruniera; Waldman, Eliseu Alves

2014-01-01

We examine the trend in causes of death among people living with AIDS in the city of São Paulo, Brazil, in the periods before and after the introduction of highly active antiretroviral therapy (HAART), and we investigate potential disparities across districts of residence. Descriptive study of three periods: pre-HAART (1991-1996); early post-HAART (1997-1999); and late post-HAART (2000-2006). The data source was the São Paulo State STD/AIDS Program and São Paulo State Data Analysis Foundation. Causes of death were classified by the ICD-9 (1991-1995) and ICD-10 (1996-2006). We estimated age-adjusted mortality rates for leading underlying causes of death and described underlying and associated causes of death according to sociodemographic characteristics and area of residence. We used Pearson's chi-square test or Fisher's exact test to compare categorical variables. Areas of residence were categorized using a socioeconomic index. To analyze trends we apply generalized linear model with Poisson regression. We evaluated 32,808 AIDS-related deaths. Between the pre- and late post-HAART periods, the proportion of deaths whose underlying causes were non-AIDS-related diseases increased from 0.2% to 9.6% (p<0.001): from 0.01% to 1.67% (p<0.001) for cardiovascular diseases; 0.01% to 1.62% (p<0.001) for bacterial/unspecified pneumonia; and 0.03% to 1.46% (p<0.001) for non-AIDS-defining cancers. In the late post-HAART period, the most common associated causes of death were bacterial/unspecified pneumonia (35.94%), septicemia (33.46%), cardiovascular diseases (10.11%) and liver diseases (8.0%); and common underlying causes, besides AIDS disease, included non-AIDS-defining cancers in high-income areas, cardiovascular diseases in middle-income areas and assault in low-income areas. The introduction of HAART has shifted the mortality profile away from AIDS-related conditions, suggesting changes in the pattern of morbidity, but heterogeneously according to area of residence. There is a need for public policies aimed at adapting health care services to address the new scenario.

Ischemic stroke due to embolic heart diseases and associated factors in Benin hospital setting.

PubMed

Gnonlonfoun, Dieudonné; Adjien, Constant; Gnimavo, Ronald; Goudjinou, Gérard; Hotcho, Corine; Nyangui Mapaga, Jennifer; Sowanou, Arlos; Gnigone, Pupchen; Domingo, Rodrigue; Houinato, Dismand

2018-04-15

Poor access to cardiovascular checkups is a major cause of ignorance of embolic heart diseases as the etiology for ischemic stroke. Study ischemic strokes due to embolic heart diseases and their associated factors. It was a cross-sectional, prospective, descriptive and analytical study conducted from November 1, 2014 to August 31, 2015 on 104 patients with ischemic stroke confirmed through brain imaging. Embolic heart diseases included arrhythmia due to atrial fibrillation (AF), atrial flutter, myocardial infarction (MI), heart valve diseases and atrial septal aneurysm (ASA). The dependent variable was embolic heart disease while independent variables encompassed socio-demographic factors, patients' history, and lifestyle. Data analysis was carried out through SAS 9.3. The rate of embolic heart diseases (EHD) as etiology for ischemic stroke was 26% (28/104). AF accounted for 69% of embolic heart diseases and 22.8% of etiologies for ischemic stroke. Ischemic strokes prevalence was 3.5%, 2.5% and 1.2% respectively for heart valve diseases, MI and ASA. The associated factor was age (p=0.000). The diagnosis of a potential cardiac source of embolism is essential because of therapeutic and prognostic implications. Wherefore, there is need for cardiovascular examination particularly Holter ECG and cardiac ultrasound examination which are not always accessible to our populations. Copyright © 2018 Elsevier B.V. All rights reserved.

A Novel Truncating LMNA Mutation in Patients with Cardiac Conduction Disorders and Dilated Cardiomyopathy.

PubMed

Kawakami, Hiroshi; Ogimoto, Akiyoshi; Tokunaga, Naohito; Nishimura, Kazuhisa; Kawakami, Hideo; Higashi, Haruhiko; Iio, Chiharuko; Kono, Tamami; Aono, Jun; Uetani, Teruyoshi; Nagai, Takayuki; Inoue, Katsuji; Suzuki, Jun; Ikeda, Shuntaro; Okura, Takafumi; Ohyagi, Yasumasa; Tabara, Yasuharu; Higaki, Jitsuo

2018-05-30

The cardiac phenotype of laminopathies is characterized by cardiac conduction disorders (CCDs) and dilated cardiomyopathy (DCM). Although laminopathies have been considered monogenic, they exhibit a remarkable degree of clinical variability. This case series aimed to detect the causal mutation and to investigate the causes of clinical variability in a Japanese family with inherited CCD and DCM.Of the five family members investigated, four had either CCD/DCM or CCD alone, while one subject had no cardiovascular disease and acted as a normal control. We performed targeted resequencing of 174 inherited cardiovascular disease-associated genes in this family and pathological mutations were confirmed using Sanger sequencing. The degree of clinical severity and variability were also evaluated using long-term medical records. We discovered a novel heterozygous truncating lamin A/C (LMNA) mutation (c.774delG) in all four subjects with CCD. Because this mutation was predicted to cause a frameshift mutation and premature termination (p.Gln258HisfsTer222) in LMNA, we believe that this LMNA mutation was the causal mutation in this family with CCD and laminopathies. In addition, gender-specific intra-familiar clinical variability was observed in this Japanese family where affected males exhibited an earlier onset of CCD and more severe DCM compared to affected females. Using targeted resequencing, we discovered a novel truncating LMNA mutation associated with CCD and DCM in this family characterized by gender differences in clinical severity in LMNA carriers. Our results suggest that in patients with laminopathy, clinical severity may be the result of multiple factors.

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.

Spatial Random Effects Survival Models to Assess Geographical Inequalities in Dengue Fever Using Bayesian Approach: a Case Study

NASA Astrophysics Data System (ADS)

Astuti Thamrin, Sri; Taufik, Irfan

2018-03-01

Dengue haemorrhagic fever (DHF) is an infectious disease caused by dengue virus. The increasing number of people with DHF disease correlates with the neighbourhood, for example sub-districts, and the characteristics of the sub-districts are formed from individuals who are domiciled in the sub-districts. Data containing individuals and sub-districts is a hierarchical data structure, called multilevel analysis. Frequently encountered response variable of the data is the time until an event occurs. Multilevel and spatial models are being increasingly used to obtain substantive information on area-level inequalities in DHF survival. Using a case study approach, we report on the implications of using multilevel with spatial survival models to study geographical inequalities in all cause survival.

Elucidating the Mechanism of Gain of Toxic Function from Mutant C1 Inhibitor Proteins in Hereditary Angioedema

DTIC Science & Technology

2016-10-01

this is due, at least in part, to an additional acquired GOTF defect caused by the mutant protein that interferes with the secretion of WT C1INH. Our...overall hypothesis is that mutant C1INH proteins exert a variable GOTF phenotype that inhibit secretion of WT C1INH protein and worsen disease...will assess the mechanisms of the GOTF with a hypothesis that misfolding of mutant C1INH protein in the ER causes impairment of WT C1INH secretion

Search and retrieval of medical images for improved diagnosis of neurodegenerative diseases

NASA Astrophysics Data System (ADS)

Ekin, Ahmet; Jasinschi, Radu; Turan, Erman; Engbers, Rene; van der Grond, Jeroen; van Buchem, Mark A.

2007-01-01

In the medical world, the accuracy of diagnosis is mainly affected by either lack of sufficient understanding of some diseases or the inter-, and/or intra-observer variability of the diagnoses. The former requires understanding the progress of diseases at much earlier stages, extraction of important information from ever growing amounts of data, and finally finding correlations with certain features and complications that will illuminate the disease progression. The latter (inter-, and intra- observer variability) is caused by the differences in the experience levels of different medical experts (inter-observer variability) or by mental and physical tiredness of one expert (intra-observer variability). We believe that the use of large databases can help improve the current status of disease understanding and decision making. By comparing large number of patients, some of the otherwise hidden relations can be revealed that results in better understanding, patients with similar complications can be found, the diagnosis and treatment can be compared so that the medical expert can make a better diagnosis. To this effect, this paper introduces a search and retrieval system for brain MR databases and shows that brain iron accumulation shape provides additional information to the shape-insensitive features, such as the total brain iron load, that are commonly used in the clinics. We propose to use Kendall's correlation value to automatically compare various returns to a query. We also describe a fully automated and fast brain MR image analysis system to detect degenerative iron accumulation in brain, as it is the case in Alzheimer's and Parkinson's. The system is composed of several novel image processing algorithms and has been extensively tested in Leiden University Medical Center over so far more than 600 patients.

Thrombotic microangiopathy: An unusual cause of renal failure in rheumatoid arthritis.

PubMed

Sakthirajan, R; Dhanapriya, J; Dineshkumar, T; Gopalakrishnan, N; Murugan, S; Balasubramaniyan, T

2017-01-01

Rheumatoid arthritis (RA) is one of the commonest rheumatological diseases. Renal involvement is not common but can occur as a result of chronic inflammation as part of disease process or drug toxicity. Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. Only a few cases of TMA in patients with RA were reported to date. We describe a 45-year-old female patient with RA who presented with oliguria and edema. Renal biopsy showed TMA with patchy cortical necrosis. She improved with hemodialysis and plasmapheresis.

[New infectious diseases in Finland--caused by climate change?].

PubMed

Vapalahti, Olli; Ruuhela, Reija; Henttonen, Heikki

2012-01-01

Although the appearance and spreading of most new infectious diseases are likely to be due to globalization or socio-economic changes, the occurrence of tick-, insect- and rodent-borne infections is at least partially dependent on climate variability and change. Climate influences the distribution and life cycle of vectors of arthropod-borne viruses as well as viral evolution and efficacy of transmission. The natural circulation of many pathogens and the development of epidemics are dependent on complex ecological factors, such as biodiversity and predator-prey cycles that in turn are indirectly linked to climate.

Epidemiology of Invasive Mold Infections in Allogeneic Stem Cell Transplant Recipients: Biological Risk Factors for Infection According to Time after Transplantation

PubMed Central

Garcia-Vidal, Carol; Upton, Arlo; Kirby, Katharine A.; Marr, Kieren A.

2009-01-01

Background Invasive mold infections (IMIs) are common in individuals who have undergone hematopoietic stem cell transplantation (HSCT). We sought to determine clinical and biological risk factors for different IMIs during each period (early and late) after allogeneic HSCT. Methods Cases of proven and probable IMI diagnosed in HSCT recipients at the Fred Hutchinson Cancer Research Center (Seattle, WA) from 1 January 1998 through 31 December 2002 were included. Survival was estimated with Kaplan-Meier curves, and Cox regression models were used for multivariable analyses. Results During the study period, 1248 patients underwent allogeneic HSCT; 163 (13.1%) received a diagnosis of probable or proven IMI. The majority of cases were caused by Aspergillus species (88%). The incidence of IMI caused by other molds remained low (<2%) over the 4-year study period. Risk factors for IMI early after HSCT and late after HSCT differed, with host variables (age) and transplant variables (human leukocyte antigen match) predominating as early risk factors and other clinical complications (graft-versus-host disease and cytomegalovirus disease) predominating later. Biological risk factors that were important during all periods included multiple cytopenias (neutropenia, lymphopenia, and monocytopenia) and iron overload. Conclusions Risk factors for invasive aspergillosis after allogeneic HSCT are multifactorial and differ according to timing after HSCT. Increased attention should be placed on understanding the immunopathogenesis of fungal disease after HSCT. PMID:18781877

Thermoneutrality, Mice, and Cancer: A Heated Opinion.

PubMed

Hylander, Bonnie L; Repasky, Elizabeth A

2016-04-01

The 'mild' cold stress caused by standard sub-thermoneutral housing temperatures used for laboratory mice in research institutes is sufficient to significantly bias conclusions drawn from murine models of several human diseases. We review the data leading to this conclusion, discuss the implications for research and suggest ways to reduce problems in reproducibility and experimental transparency caused by this housing variable. We have found that these cool temperatures suppress endogenous immune responses, skewing tumor growth data and the severity of graft versus host disease, and also increase the therapeutic resistance of tumors. Owing to the potential for ambient temperature to affect energy homeostasis as well as adrenergic stress, both of which could contribute to biased outcomes in murine cancer models, housing temperature should be reported in all publications and considered as a potential source of variability in results between laboratories. Researchers and regulatory agencies should work together to determine whether changes in housing parameters would enhance the use of mouse models in cancer research, as well as for other diseases. Finally, for many years agencies such as the National Cancer Institute (NCI) have encouraged the development of newer and more sophisticated mouse models for cancer research, but we believe that, without an appreciation of how basic murine physiology is affected by ambient temperature, even data from these models is likely to be compromised. Copyright © 2016 Elsevier Inc. All rights reserved.

Climate Teleconnections and Recent Patterns of Human and Animal Disease Outbreaks

NASA Technical Reports Server (NTRS)

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

2011-01-01

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. Extremes in rainfall (drought and flood) during the period 2004 - 2009 have privileged different disease vectors. Chikungunya outbreaks occurred during the severe drought from late 2004 to 2006 over coastal East Africa and the western Indian Ocean islands and in the later years India and Southeast Asia. The chikungunya pandemic was caused by a Central/East African genotype that appears to have been precipitated and then enhanced by global-scale and regional climate conditions in these regions. Outbreaks of Rift Valley fever occurred following excessive rainfall period from late 2006 to late 2007 in East Africa and Sudan, and then in 2008 - 2009 in Southern Africa. The shift in the outbreak patterns of Rift Valley fever from East Africa to Southern Africa followed a transition of the El Nino/Southern Oscillation (ENSO) phenomena from the warm El Nino phase (2006-2007) to the cold La Nina phase (2007-2009) and associated patterns of variability in the greater Indian Ocean basin that result in the displacement of the centres of above normal rainfall from Eastern to Southern Africa. Understanding the background patterns of climate variability both at global and regional scale and their impacts on ecological drivers of vector borne-diseases is critical in long-range planning of appropriate response and mitigation measures.

EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

PubMed Central

McGuigan, David B.; Heon, Elise; Cideciyan, Artur V.; Ratnapriya, Rinki; Lu, Monica; Sumaroka, Alexander; Roman, Alejandro J.; Batmanabane, Vaishnavi; Garafalo, Alexandra V.; Stone, Edwin M.; Jacobson, Samuel G.

2017-01-01

Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT), and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit), some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK. PMID:28704921

Emerging and re-emerging infectious diseases in Iran

PubMed Central

Parhizgari, Najmeh; Gouya, Mohammad Mehdi; Mostafavi, Ehsan

2017-01-01

Despite development of preventive and controlling strategies regarding infectious diseases, they are still considered as one of the most significant leading causes of morbidity and mortality, worldwide. Changes in humans’ demographics and behaviors, microbial and ecological alterations, agricultural development, international travels and susceptibility to infectious diseases have resulted in increased reports of emerging infectious diseases (EIDs) and reemerging infectious diseases (RIDs) in various geographical areas. Because of the various types of geographic properties in Iran, substantial climatic variability, as well as unstable political situations and poor public health conditions in some of neighboring countries, EIDs and RIDs are serious public health problems; among them, zoonotic and drug resistant diseases are the most significant. Hence, this review provides an overview of the significant bacterial, viral and fungal EIDs and RIDs in Iran regarding their epidemiological aspects. PMID:29225752

Effects of global climate on infectious disease: the cholera model.

PubMed

Lipp, Erin K; Huq, Anwar; Colwell, Rita R

2002-10-01

Recently, the role of the environment and climate in disease dynamics has become a subject of increasing interest to microbiologists, clinicians, epidemiologists, and ecologists. Much of the interest has been stimulated by the growing problems of antibiotic resistance among pathogens, emergence and/or reemergence of infectious diseases worldwide, the potential of bioterrorism, and the debate concerning climate change. Cholera, caused by Vibrio cholerae, lends itself to analyses of the role of climate in infectious disease, coupled to population dynamics of pathogenic microorganisms, for several reasons. First, the disease has a historical context linking it to specific seasons and biogeographical zones. In addition, the population dynamics of V. cholerae in the environment are strongly controlled by environmental factors, such as water temperature, salinity, and the presence of copepods, which are, in turn, controlled by larger-scale climate variability. In this review, the association between plankton and V. cholerae that has been documented over the last 20 years is discussed in support of the hypothesis that cholera shares properties of a vector-borne disease. In addition, a model for environmental transmission of cholera to humans in the context of climate variability is presented. The cholera model provides a template for future research on climate-sensitive diseases, allowing definition of critical parameters and offering a means of developing more sophisticated methods for prediction of disease outbreaks.

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

Age of child, more than HPV type, is associated with clinical course in recurrent respiratory papillomatosis.

PubMed

Buchinsky, Farrel J; Donfack, Joseph; Derkay, Craig S; Choi, Sukgi S; Conley, Stephen F; Myer, Charles M; McClay, John E; Campisi, Paolo; Wiatrak, Brian J; Sobol, Steven E; Schweinfurth, John M; Tsuji, Domingos H; Hu, Fen Z; Rockette, Howard E; Ehrlich, Garth D; Post, J Christopher

2008-05-28

RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV) 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with at least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher than that of patients with HPV 6 (Fisher's exact p = 0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p = 0.014). Both by multiple linear regression and by multiple logistic regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. CONCLUSIONS/SIGNIFICANCE ABSTRACT: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course.

Predicting Pre-planting Risk of Stagonospora nodorum blotch in Winter Wheat Using Machine Learning Models.

PubMed

Mehra, Lucky K; Cowger, Christina; Gross, Kevin; Ojiambo, Peter S

2016-01-01

Pre-planting factors have been associated with the late-season severity of Stagonospora nodorum blotch (SNB), caused by the fungal pathogen Parastagonospora nodorum, in winter wheat (Triticum aestivum). The relative importance of these factors in the risk of SNB has not been determined and this knowledge can facilitate disease management decisions prior to planting of the wheat crop. In this study, we examined the performance of multiple regression (MR) and three machine learning algorithms namely artificial neural networks, categorical and regression trees, and random forests (RF), in predicting the pre-planting risk of SNB in wheat. Pre-planting factors tested as potential predictor variables were cultivar resistance, latitude, longitude, previous crop, seeding rate, seed treatment, tillage type, and wheat residue. Disease severity assessed at the end of the growing season was used as the response variable. The models were developed using 431 disease cases (unique combinations of predictors) collected from 2012 to 2014 and these cases were randomly divided into training, validation, and test datasets. Models were evaluated based on the regression of observed against predicted severity values of SNB, sensitivity-specificity ROC analysis, and the Kappa statistic. A strong relationship was observed between late-season severity of SNB and specific pre-planting factors in which latitude, longitude, wheat residue, and cultivar resistance were the most important predictors. The MR model explained 33% of variability in the data, while machine learning models explained 47 to 79% of the total variability. Similarly, the MR model correctly classified 74% of the disease cases, while machine learning models correctly classified 81 to 83% of these cases. Results show that the RF algorithm, which explained 79% of the variability within the data, was the most accurate in predicting the risk of SNB, with an accuracy rate of 93%. The RF algorithm could allow early assessment of the risk of SNB, facilitating sound disease management decisions prior to planting of wheat.

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.

Pathogenicity for onion and genetic diversity of isolates of the pathogenic fungus Colletotrichum gloeosporioides (Phyllachoraceae) from the State of Pernambuco, Brazil.

PubMed

Nova, M X Vila; Borges, L R; de Sousa, A C B; Brasileiro, B T R V; Lima, E A L A; da Costa, A F; de Oliveira, N T

2011-02-22

Onion anthracnose, caused by Colletotrichum gloeosporioides, is one of the main diseases of onions in the State of Pernambuco. We examined the pathogenicity of 15 C. gloeosporioides strains and analyzed their genetic variability using RAPDs and internal transcribed spacers (ITS) of the rDNA region. Ten of the strains were obtained from substrates and hosts other than onion, including chayote (Sechium edule), guava (Psidium guajava), pomegranate (Punica granatum), water from the Capibaribe River, maracock (Passiflora sp), coconut (Cocus nucifera), surinam cherry (Eugenia uniflora), and marine soil; five isolates came from onions collected from four different regions of the State of Pernambuco and one region of the State of Amazonas. Pathogenicity tests were carried out using onion leaves and bulbs. All strains were capable of causing disease in leaves, causing a variable degree of lesions on the leaves; four strains caused the most severe damage. In the onion bulb tests, only three of the above strains caused lesions. Seven primers of arbitrary sequences were used in the RAPD analysis, generating polymorphic bands that allowed the separation of the strains into three distinct groups. The amplification products generated with the primers ITS1 and ITS4 also showed polymorphism when digested with three restriction enzymes, DraI, HaeIII and MspI. Only the latter two demonstrated genetic variations among the strains. These two types of molecular markers were able to differentiate the strain from the State of Amazonas from those of the State of Pernambuco. However, there was no relationship between groups of strains, based on molecular markers, and degree of pathogenicity for onion leaves and bulbs.

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.

[Lung disorders due to metals].

PubMed

Rüegger, M

1995-03-11

Though metals represent the largest group of elements they rather rarely cause respiratory diseases. This article will therefore review the most important ones caused by inhaled dusts of metals and some of their inorganic compounds, but leaving aside silicosis and silicatosis as well as iatrogenically induced metal pneumopathies. Among toxic inflammatory diseases metal fume fever, an influenza-like condition caused by zinc oxide, ranks as the commonest. Activities such as oxi-acetylene cutting and welding of zinc covered metal pieces account for about 90% of all cases compensated in Switzerland. Due to the non-recurrent character of this type of work, the typical waning of symptoms while exposure is going on has become seldom. Toxic pneumonia caused by inhaled metal fumes occurs rather seldom. However, serious cases have been reported where soldiers were exposed to zinc chloride from smoke bombs. The existence and extent of chronic airflow limitation due to occupational exposure to metallic dusts have not been widely examined but are to be assumed when there is poor occupational hygiene. Concerning asthma, there are at least four metals and several of their compounds which have been proven to cause variable airway narrowing, namely chromium, nickel, platinum and cobalt (the latter as hardmetal). Platinum complex salts (chloro-compounds) are very potent sensitizers leading to a notable prevalence of asthma among exposed workforces. Nevertheless, there have been no such cases in Switzerland for more than ten years. Hard-metal not only causes asthma but also an alveolitis-like interstitial lung disease progressing to fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular Typing of Pneumococci for Investigation of Linked Cases of Invasive Pneumococcal Disease ▿

PubMed Central

Pichon, Bruno; Moyce, Laura; Sheppard, Carmen; Slack, Mary; Turbitt, Deborah; Pebody, Richard; Spencer, David A.; Edwards, Justin; Krahé, Daniel; George, Robert

2010-01-01

In winter 2007-2008, an outbreak of pediatric pneumonia caused by serotype 5 pneumococci was identified in a northeast London suburb. Variable number of tandem repeat analyses clustered these pneumococci from the other serotype 5 pneumococci in the United Kingdom, highlighting the importance of this discriminative typing method in supporting epidemiological investigations. PMID:20164267

Epidemiology and Natural History of Non-alcoholic Fatty Liver Disease

PubMed Central

Mishra, Alita; Younossi, Zobair M

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease burden across the world. By definition, although the histopathologic features of NAFLD are identical to that of alcoholic liver disease, its diagnosis requires absence of significant alcohol use and absence of other causes of chronic liver disease. We now know that NAFLD is not simply a disease of the Western world. It is manifested across the world, in varying rates, across gender, across varying ethnicities, and in its association with other host factors. In this review article, the definition of NAFLD, its spectrum, ranging from mild steatosis to hepatocellular injury and inflammation defined as non-alcoholic steatohepatitis (NASH) is discussed. Mild steatosis is generally a stable disease whereas NASH can be progressive. Based on current published literature, current incidence and prevalence of NAFLD and NASH are discussed. It is also accepted that these processes will continue to increase in prevalence with the rise of obesity, type II diabetes, and associated metabolic syndrome. Some of the risk factors have been well-established and are discussed. In addition, this review also presents emerging associations with other risk factors for NAFLD. Natural history of NAFLD is variable depending upon the histologic subtypes and other underlying comorbidities and is discussed in this review as well. PMID:25755422

Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis

PubMed Central

Sun, Xingshen; Sui, Hongshu; Fisher, John T.; Yan, Ziying; Liu, Xiaoming; Cho, Hyung-Ju; Joo, Nam Soo; Zhang, Yulong; Zhou, Weihong; Yi, Yaling; Kinyon, Joann M.; Lei-Butters, Diana C.; Griffin, Michelle A.; Naumann, Paul; Luo, Meihui; Ascher, Jill; Wang, Kai; Frana, Timothy; Wine, Jeffrey J.; Meyerholz, David K.; Engelhardt, John F.

2010-01-01

Cystic fibrosis (CF) is a recessive disease that affects multiple organs. It is caused by mutations in CFTR. Animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR-knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments. PMID:20739752

Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis.

PubMed

Sun, Xingshen; Sui, Hongshu; Fisher, John T; Yan, Ziying; Liu, Xiaoming; Cho, Hyung-Ju; Joo, Nam Soo; Zhang, Yulong; Zhou, Weihong; Yi, Yaling; Kinyon, Joann M; Lei-Butters, Diana C; Griffin, Michelle A; Naumann, Paul; Luo, Meihui; Ascher, Jill; Wang, Kai; Frana, Timothy; Wine, Jeffrey J; Meyerholz, David K; Engelhardt, John F

2010-09-01

Cystic fibrosis (CF) is a recessive disease that affects multiple organs. It is caused by mutations in CFTR. Animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR-knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments.

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.

Unraveling human complexity and disease with systems biology and personalized medicine

PubMed Central

Naylor, Stephen; Chen, Jake Y

2010-01-01

We are all perplexed that current medical practice often appears maladroit in curing our individual illnesses or disease. However, as is often the case, a lack of understanding, tools and technologies are the root cause of such situations. Human individuality is an often-quoted term but, in the context of human biology, it is poorly understood. This is compounded when there is a need to consider the variability of human populations. In the case of the former, it is possible to quantify human complexity as determined by the 35,000 genes of the human genome, the 1–10 million proteins (including antibodies) and the 2000–3000 metabolites of the human metabolome. Human variability is much more difficult to assess, since many of the variables, such as the definition of race, are not even clearly agreed on. In order to accommodate human complexity, variability and its influence on health and disease, it is necessary to undertake a systematic approach. In the past decade, the emergence of analytical platforms and bioinformatics tools has led to the development of systems biology. Such an approach offers enormous potential in defining key pathways and networks involved in optimal human health, as well as disease onset, progression and treatment. The tools and technologies now available in systems biology analyses offer exciting opportunities to exploit the emerging areas of personalized medicine. In this article, we discuss the current status of human complexity, and how systems biology and personalized medicine can impact at the individual and population level. PMID:20577569

[Introduction to Genetic/Rare Disease and the Application of Genetic Counseling].

PubMed

Chu, Shao-Yin; Weng, Chun-Ying

2017-10-01

Genetic disease or hereditary disease is a group of disorders that is caused by mutations in an individual's genome. The mutated genome or gene may be transmitted through the germ line during reproduction, causing certain recurrence risk in offspring and other family members. The heritability of these disorders is thus an important issue to deal with clinically. In Taiwan, a rare disease is defined as a disease that is prevalent in fewer than 1 in 10,000 individuals. As up to 80% of rare disease cases in Taiwan are genetic disease disorders, genetic disease may not rare. The pathophysiology of genetic/ rare disease is very complicated. Individual disorders may have their own unique mechanisms (such as Fragile X syndrome), with most of these mechanisms still unclear or unknown. The symptoms and signs of genetic/rare disease thus present the greatest variabilities and cause difficulties in making diagnoses. Most related patients may present multiple congenital anomalies, metabolic disorders, growth and developmental delays, defects in cognition, neuromuscular abnormalities, and defects in vision, hearing or other organ functions. Symptomatic and supportive treatment still comprise a major component of treatment of genetic/rare disease (with the exception of special formulae for several inborn errors of metabolic disease and enzyme replacement therapy in some lysosomal storage disease). Poor self-care ability is common and the burden on caregivers is huge. Most rare disease patients are treated using a comprehensive rehabilitation program that begins during very early childhood, receive individual educational programs, and are continuously monitored with regard to their growth, developmental, and nutritional status. Inter-professional patient care, genetic counseling, and the creation of family support networks play an important role in family management. Public awareness and the creation of appropriate social systems and resources allocation are mandatory for proper care. The incidence of each genetic/rare disease is rare, but collectively they are important public health issue and a challenge to medical care.

Screening for mutations in rhodopsin and peripherin/RDS in patients with autosomal dominant retinitis pigmentosa

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

Rodriguez, J.A.; Gannon, A.M.; Daiger, S.P.

1994-09-01

Mutations in rhodopsin account for approximately 30% of all cases of autosomal dominant retinits pigmentosa (adRP) and mutations in peripherin/RDS account for an additional 5% of cases. Also, mutations in rhodopsin can cause autosomal recessive retinitis pigmentosa and mutations in peripherin/RDS can cause dominant macular degeneration. Most disease-causing mutations in rhodopsin and peripherin/RDS are unique to one family or, at most, to a few families within a limited geographic region, though a few mutations are found in multiple, unrelated families. To further determine the spectrum of genetic variation in these genes, we screened DNA samples from 134 unrelated patients withmore » retinitis pigmentosa for mutations in both rhodopsin and peripherin/RDS using SSCP followed by genomic sequencing. Of the 134 patients, 86 were from families with apparent adRP and 48 were either isolated cases or were from families with an equivocal mode of inheritance. Among these patients we found 14 distinct rhodopsin mutations which are likely to cause retinal disease. Eleven of these mutations were found in one individual or one family only, whereas the Pro23His mutation was found in 14 {open_quotes}unrelated{close_quotes}individuals. The splice-site mutation produces dominant disease though with highly variable expression. Among the remaining patients were found 6 distinct peripherin/RDS mutations which are likely to cause retinal disease. These mutations were also found in one patient or family only, except the Gly266Asp mutation which was found in two unrelated patients. These results confirm the expected frequency and broad spectrum of mutations causing adRP.« less

Self-reported functional, communicative, and critical health literacy on foodborne diseases in Accra, Ghana.

PubMed

Gupta, Sangeeta; Tutu, Raymond Asare; Boateng, John; Busingye, Janice Desire; Elavarthi, Sathya

2018-01-01

Although substantial progress has been made in reducing total mortality resulting from foodborne diseases, diarrheal illness are still the second most common illnesses among children. In Ghana, foodborne diseases have consistently been among the top 20 causes of outpatient illness over the last couple of decades. This study, therefore, examines health literacy on foodborne diseases and the relative effects of health literacy on self-rated health. Foodborne diseases are major causes of morbidity and mortality globally. A mixed-method approach was used for this study. A survey questionnaire and an in-depth interview guideline were administered to samples of 401 and 30 individuals, respectively. We undertook reliability and validity analyses. ANOVA and chi-square tests were undertaken to assess bivariate association between health literacy and demographic variables as well as health status. Ordinal logistic regression models were used to examine the relative effects of health literacy on self-rated health status controlling for individual characteristics. The instrument was internally consistent (Cronbach alpha = 0.744) and valid. On health literacy, 40% of the respondents reported not to require help when they are given information on foodborne diseases to read by a doctor, nurse, or pharmacist. Approximately 60% of respondents need help with completing or filling out hospital documents. Educational level was found to be positively related to functional health literacy. Ordinal logit regression models showed that health literacy is a predictor of self-rated health after controlling for demographic variables. Functional literacy is relatively low in the community. There is a positive association between educational level and functional health literacy. The study has also demonstrated the direct positive relationship between health literacy and health status controlling for covariates. Subsequent studies will need to examine multiple level dimensions of health literacy with direct link between specific foodborne diseases and health literacy.

Metabolic Bone Disease in the Context of Metastatic Neuroendocrine Tumor: Differentiation from Skeletal Metastasis, the Molecular PET-CT Imaging Features, and Exploring the Possible Etiopathologies Including Parathyroid Adenoma (MEN1) and Paraneoplastic Humoral Hypercalcemia of Malignancy Due to PTHrP Hypersecretion.

PubMed

Ranade, Rohit; Basu, Sandip

2017-01-01

Three cases of metabolic bone disease in the setting of metastatic neuroendocrine tumor (NET) are illustrated with associated etiopathologies.  One of these cases harbored mixed lesions in the form of vertebral metastasis (biopsy proven) while the other skeletal lesions were caused due to metabolic bone disease related to multiple parathyroid adenomas. While the metastatic lesion was positive on 68Ga-DOTATATE positron emission tomography-computed tomography (PET-CT), the lesions of metabolic bone disease were negative and the 18F-fluoride PET-CT demonstrated the features of metabolic bone scan. Similar picture of metabolic bone disease [18-sodium fluoride (18NaF)/68Ga-DOTATATE mismatch] was documented in the other two patients, while fluorodeoxyglucose (FDG)-PET-CT was variably positive, primarily showing tracer uptake in the metabolic skeletal lesions of the patient with hypersecretion of parathyroid hormone-related protein (PTHrP) by the underlying tumor. Discordance between 18NaF PET-CT and 68Ga-DOTATATE PET-CT serves as a good marker for identification of metabolic bone disease and diagnosing such a clinical entity. In a patient of NET with metabolic bone disease and hypercalcemia, thus, two causes need to be considered: (i) Coexisting parathyroid adenoma in multiple endocrine neoplasia type I (MEN-I) syndrome and (ii) humoral hypercalcemia of malignancy (HHM) related to hypersecretion of PTHrP by the tumor. The correct diagnosis of metabolic bone disease in metastatic NET can alter the management substantially. Interestingly, peptide receptor radionuclide therapy (PRRT) can emerge as a very promising treatment modality in patients of metabolic bone disease caused by HHM in the setting of NET.

Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane.

PubMed

Funk, Steven D; Lin, Meei-Hua; Miner, Jeffrey H

2018-04-16

The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy. Mutations in LAMB2 that impact the synthesis or function of laminin α5β2γ1 (LM-521) cause Pierson syndrome (congenital nephrotic syndrome with eye and neurological defects) and its less severe variants, including isolated congenital nephrotic syndrome. The very different types of kidney diseases that result from mutations in collagen IV vs. laminin are likely due to very different pathogenic mechanisms. A better understanding of these mechanisms should lead to targeted therapeutic approaches that can help people with these rare but important diseases. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Coronary heart disease: pandemic in a true sense.

PubMed

Rambiharilal Shrivastava, Saurabh; Saurabh Shrivastava, Prateek; Ramasamy, Jegadeesh

2013-01-01

Cardiovascular diseases are caused because of abnormalities in the heart and blood vessels. Recent trends reveal that the incidence of coronary heart disease (CHD) has gradually decreased in many developed countries, but the situation remains quite challenging in developing nations that account for more than 60% of the global burden. Multiple socio-demographic, personal, physician related and healthcare delivery system related factors have been identified which act in variable combinations to either influence the incidence of CHD or affect the short/long-term outcome of the disease. Of all CHD cases who succumb within 28 days of onset of symptoms, almost 67% fail to reach even a hospital. This clearly signifies the importance of primary prevention and early recognition of the warning signs in averting cause-specific mortality. The main priority is to develop cost-effective equitable health care innovations in CHD prevention and to monitor the trend of CHD so that evidence-based interventions can be formulated. To conclude, inculcating health-promoting behaviors in school children and the general population by means of community-based health screening and education interventions could avert many more deaths attributed to CHDs.

Campylobacteriosis - an overview.

PubMed

Sarkar, S R; Hossain, M A; Paul, S K; Ray, N C; Sultana, S; Rahman, M M; Islam, A

2014-01-01

Campylobacteriosis is a collective term, used for infectious, emerging foodborne disease caused by Campylobacter species comprising Gram negative, curved, and microaerophilic pathogens. The true incidence of human campylobacteriosis is unknown for most countries of the world including Bangladesh. But campylobacteriosis is not uncommon in our country. Due to its increasing incidence in many countries of the world, it is an important issue now a day. Animals such as birds are the main sources of infection. Farm animals such as cattle, poultry are commonly infected from such sources and raw milk, undercooked or poorly handled meat becomes contaminated. Transmission of campylobacteriosis to human occurs through consumption of infected, unpasteurized animal milk and milk products, undercooked poultry and through contaminated drinking water. Contact with contaminated poultry, livestock or household pets, especially puppies, can also cause disease. Due to variability of clinical features and limited availability of laboratory facilities, the disease remains largely under-reported. Early and specific diagnosis is important to ensure a favourable outcome regarding this food borne disease. Antibiotic treatment is controversial, and has only a benefit on the duration of symptoms. Campylobacter infections can be prevented by some simple hygienic food handling practices.

Relationship between the fungal complex causing Fusarium head blight of wheat and environmental conditions.

PubMed

Xu, X-M; Nicholson, P; Thomsett, M A; Simpson, D; Cooke, B M; Doohan, F M; Brennan, J; Monaghan, S; Moretti, A; Mule, G; Hornok, L; Beki, E; Tatnell, J; Ritieni, A; Edwards, S G

2008-01-01

ABSTRACT Over 4 years, the environmental conditions and the causal agents of Fusarium head blight (FHB) disease of wheat were determined in field sites in four European countries: Hungary, Ireland, Italy, and the United Kingdom. Polymerase chain reaction-based methods were used to detect each species causing FHB and quantify its DNA (as a measurement of fungal abundance) in the samples. Canonical correspondence analysis (CCA) was used to determine the relationship of the incidence and abundance of each species with weather variables. CCA indicated that little variability in the species prevalence data was explained by the weather variables. In contrast, a greater proportion of variability in abundance data was accounted for by the weather variables. Most samples contained two or more species and statistical analysis suggested that these species tended to coexist at field sites. CCA also indicated that there were differences in the relationships of the prevalence and abundance of the six FHB species with environmental variables. Fusarium poae was associated with relatively drier and warmer conditions, whereas F. graminearum was associated with warmer/humid conditions. F. avenaceum and F. culmorum were both associated with niches of cooler/wet/humid conditions. Two Microdochium species were associated with regions of relatively cool/moderate temperatures and frequent rainfalls of short duration. The results also suggested that environmental conditions differentially affect the infection and colonization processes, and the comparative abundance of the six species.

Death certificate data and causes of death in patients with parkinsonism.

PubMed

Moscovich, Mariana; Boschetti, Gabriela; Moro, Adriana; Teive, Helio A G; Hassan, Anhar; Munhoz, Renato P

2017-08-01

Assessment of variables related to mortality in Parkinson disease (PD) and other parkinsonian syndromes relies, among other sources, on accurate death certificate (DC) documentation. We assessed the documentation of the degenerative disorder on DCs and evaluated comorbidities and causes of death among parkinsonian patients. Demographic and clinical data were systematically and prospectively collected on deceased patients followed at a tertiary movement disorder clinic. DCs data included the documentation of parkinsonism, causes, and place of death. Among 138 cases, 84 (60.9%) male, mean age 77.9 years, mean age of onset 66.7, and mean disease duration 10.9 years. Clinical diagnoses included PD (73.9%), progressive supranuclear palsy (10.9%), multiple system atrophy (7.2%), Lewy body dementia (7.2%) and corticobasal degeneration (0.7%). Psychosis occurred in 60.1% cases, dementia in 48.5%. Most PD patients died due to heterogeneous causes before reaching advanced stages. Non-PD parkinsonian patients died earlier due to causes linked to the advanced neurodegenerative process. PD was documented in 38.4% of DCs with different forms of inconsistencies. That improved, but remained significant when it was signed by a specialist. More than half of PD cases died while still ambulatory and independent, after a longer disease course and due to causes commonly seen in that age group. Deaths among advanced PD patients occurred due to causes similar to what we found in non-PD cases. These findings can be useful for clinical, prognostic and counseling purposes. Underlying parkinsonian disorders are poorly documented in DCs, undermining its' use as sources of data collection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Utility of Tissue Doppler Imaging in the Echocardiographic Evaluation of Left and Right Ventricular Function in Dogs with Myxomatous Mitral Valve Disease with or without Pulmonary Hypertension.

PubMed

Baron Toaldo, M; Poser, H; Menciotti, G; Battaia, S; Contiero, B; Cipone, M; Diana, A; Mazzotta, E; Guglielmini, C

2016-05-01

In human medicine, right ventricular (RV) functional parameters represent a tool for risk stratification in patients with congestive heart failure caused by left heart disease. Little is known about RV alterations in dogs with left-sided cardiac disorders. To assess RV and left ventricular (LV) function in dogs with myxomatous mitral valve disease (MMVD) with or without pulmonary hypertension (PH). One-hundred and fourteen dogs: 28 healthy controls and 86 dogs with MMVD at different stages. Prospective observational study. Animals were classified as healthy or having MMVD at different stages of severity and according to presence or absence of PH. Twenty-eight morphological, echo-Doppler, and tissue Doppler imaging (TDI) variables were measured and comparison among groups and correlations between LV and RV parameters were studied. No differences were found among groups regarding RV echo-Doppler and TDI variables. Sixteen significant correlations were found between RV TDI and left heart echocardiographic variables. Dogs with PH had significantly higher transmitral E wave peak velocity and higher E/e' ratio of septal (sMV) and lateral (pMV) mitral annulus. These 2 variables were found to predict presence of PH with a sensitivity of 84 and 72%, and a specificity of 71 and 80% at cut-off values of 10 and 9.33 for sMV E/e' and pMV E/e', respectively. No association between variables of RV function and different MMVD stage and severity of PH could be detected. Some relationships were found between echocardiographic variables of right and left ventricular function. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

[Lung transplant therapy for suppurative diseases].

PubMed

de Pablo, A; López, S; Ussetti, P; Carreño, M C; Laporta, R; López García-Gallo, C; Ferreiro, M J

2005-05-01

Lung transplantation is a valid therapeutic approach for patients with bronchiectasis. The objective of the present study was to evaluate our experience with bronchiectasis patients and compare the results in patients with cystic fibrosis to results in those with bronchiectasis caused by other processes. We carried out a retrospective study of bronchiectasis patients treated by lung transplantation in order to analyze demographic, functional and microbiological characteristics before and after transplantation, and survival. From 1991 to 2002 lung transplants were performed on 171 patients, 44 of whom had suppurative lung disease (27 had cystic fibrosis and 17 had bronchiectasis caused by other processes). There were no significant differences in the demographic variables between the 2 groups. At transplantation, lung function variables showed severe bronchial obstruction (mean [SD] forced expiratory volume in 1 second of 808 [342] mL and forced vital capacity of 1,390 [611] mL) and respiratory insufficiency (PaO2 at 52 [10] mm Hg and PaCO2 at 48 [9] mm Hg). Only PaO2 was significantly lower in patients with bronchiectasis from causes other than cystic fibrosis. Airway colonization was present in 91% of the patients; Pseudomonas spp germs were detected in 64% of the cases and were multiresistant in 9%. In the early postoperative period germs were isolated in 59% of the cases, half of which involved the same germ as had been isolated before transplantation. One year after lung transplantation, 34% of the patients continued to have bronchial colonization. Survival at 1 year was 79% and at 5 years, 49%, with no significant difference between the patients with cystic fibrosis and those with other suppurative diseases, nor between the patients with and without Pseudomonas colonization. Only 2 patients had died of bacterial pneumonia at 1 month after transplantation. Although airway colonization in patients with suppurative diseases complicates postoperative management, the results in terms of survival are good.

Ascochyta blight of chickpea: production of phytotoxins and disease management.

PubMed

Shahid, Ahmad Ali; Husnain, Tayyab; Riazuddin, Sheikh

2008-01-01

Ascochyta blight caused by Ascochyta rabiei (Pass.) Lab., is the most devastating disease of chickpea and can occur anywhere the crop is grown. Several epidemics of blight causing complete yield losses have been reported. Despite extensive pathological and molecular studies, the nature and extent of pathogenic variability in A. rabiei have not been clearly established. Several isolates of A. rabiei were grown in liquid culture medium which secreted phytotoxic compounds of solanapyrone A, B, C and cytochalasin D. The same fungal metabolites were also recovered from extract of naturally blight stricken chickpea plants. Toxicity of purified solanapyrones as determined by cell bioassay was in the order of solanapyrone A>solanapyrone B>solanapyrone C. However, the specificity of all three compounds was dependent on the genetic identity of the chickpea cultivars. Seed treatment and foliar application of fungicides are commonly recommended for disease management, but further information on biology and survival of A. rabiei is needed to devise more effective management strategies. A short description of chickpea blight, geographical distribution, disease cycle, symptoms, losses, production of phytotoxins and disease management practices for the control of Ascochyta blight will be discussed in this review article.

Dissection of Host Susceptibility to Bacterial Infections and Its Toxins.

PubMed

Nashef, Aysar; Agbaria, Mahmoud; Shusterman, Ariel; Lorè, Nicola Ivan; Bragonzi, Alessandra; Wiess, Ervin; Houri-Haddad, Yael; Iraqi, Fuad A

2017-01-01

Infection is one of the leading causes of human mortality and morbidity. Exposure to microbial agents is obviously required. However, also non-microbial environmental and host factors play a key role in the onset, development and outcome of infectious disease, resulting in large of clinical variability between individuals in a population infected with the same microbe. Controlled and standardized investigations of the genetics of susceptibility to infectious disease are almost impossible to perform in humans whereas mouse models allow application of powerful genomic techniques to identify and validate causative genes underlying human diseases with complex etiologies. Most of current animal models used in complex traits diseases genetic mapping have limited genetic diversity. This limitation impedes the ability to create incorporated network using genetic interactions, epigenetics, environmental factors, microbiota, and other phenotypes. A novel mouse genetic reference population for high-resolution mapping and subsequently identifying genes underlying the QTL, namely the Collaborative Cross (CC) mouse genetic reference population (GRP) was recently developed. In this chapter, we discuss a variety of approaches using CC mice for mapping genes underlying quantitative trait loci (QTL) to dissect the host response to polygenic traits, including infectious disease caused by bacterial agents and its toxins.

Occupational social class and mortality in a population of men economically active: the contribution of education and employment situation.

PubMed

Regidor, Enrique; Ronda, Elena; Martínez, David; Calle, M Elisa; Navarro, Pedro; Domínguez, Vicente

2005-01-01

This study examines how education and employment situation contribute to the association between a classification of occupational class based on skill assets and mortality from different causes of death. Data were obtained by linking records from the 1996 population census for Spanish men aged 35-64 residing in Madrid with 1996 and 1997 mortality records. The risk of mortality was higher in skilled, semi-skilled and unskilled workers than in higher and lower managerial and professional workers. Adjusting for educational level substantially decreased the magnitude of the gradient. The decrease in the gradient after adjusting for employment situation was much smaller. Except in the case of mortality from respiratory diseases, the mortality gradient disappeared after adjusting for both variables. These results show that education and, to a much lesser degree, employment situation explain part of the social gradient observed in mortality from all causes and from broad causes of death, except from respiratory diseases.

Tularaemia: clinical aspects in Europe.

PubMed

Maurin, Max; Gyuranecz, Miklós

2016-01-01

Tularaemia is a zoonotic disease caused by Francisella tularensis, a Gram-negative, facultative intracellular bacterium. Typically, human and animal infections are caused by F tularensis subspecies tularensis (type A) strains mainly in Canada and USA, and F tularensis subspecies holarctica (type B) strains throughout the northern hemisphere, including Europe. In the past, the epidemiological, clinical, therapeutic, and prognostic aspects of tularaemia reported in the English medical literature were mainly those that had been reported in the USA, where the disease was first described. Tularaemia has markedly changed in the past decade, and a large number of studies have provided novel data for the disease characteristics in Europe. In this Review we aim to emphasise the specific and variable aspects of tularaemia in different European countries. In particular, two natural lifecycles of F tularensis have been described in this continent, although not fully characterised, which are associated with different modes of transmission, clinical features, and public health burdens of tularaemia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential diagnosis of the scalp hair folliculitis.

PubMed

Lugović-Mihić, Liborija; Barisić, Freja; Bulat, Vedrana; Buljan, Marija; Situm, Mirna; Bradić, Lada; Mihić, Josip

2011-09-01

Scalp hair folliculitis is a relatively common condition in dermatological practice and a major diagnostic and therapeutic challenge due to the lack of exact guidelines. Generally, inflammatory diseases of the pilosebaceous follicle of the scalp most often manifest as folliculitis. There are numerous infective agents that may cause folliculitis, including bacteria, viruses and fungi, as well as many noninfective causes. Several noninfectious diseases may present as scalp hair folliculitis, such as folliculitis decalvans capillitii, perifolliculitis capitis abscendens et suffodiens, erosive pustular dermatitis, lichen planopilaris, eosinophilic pustular folliculitis, etc. The classification of folliculitis is both confusing and controversial. There are many different forms of folliculitis and several classifications. According to the considerable variability of histologic findings, there are three groups of folliculitis: infectious folliculitis, noninfectious folliculitis and perifolliculitis. The diagnosis of folliculitis occasionally requires histologic confirmation and cannot be based solely on clinical appearance of scalp lesions. This article summarizes prominent variants of inflammatory diseases of the scalp hair follicle with differential diagnosis and appertaining histological features.

National and sub-national age-sex specific and cause-specific mortality and disability-adjusted life years (DALYs) attributable to household air pollution from solid cookfuel use (HAP) in Iran, 1990-2013.

PubMed

Abtahi, Mehrnoosh; Koolivand, Ali; Dobaradaran, Sina; Yaghmaeian, Kamyar; Mohseni-Bandpei, Anoushiravan; Khaloo, Shokooh Sadat; Jorfi, Sahand; Saeedi, Reza

2017-07-01

National and sub-national mortality, years of life lost due to premature mortality (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) for household air pollution from solid cookfuel use (HAP) in Iran, 1990-2013 were estimated based on the Global Burden of Disease Study 2013 (GBD 2013). The burden of disease attributable to HAP was quantified by the comparative risk assessment method using four inputs: (1) exposure to HAP, (2) the theoretical minimum risk exposure level (TMREL), (3) exposure-response relationships of related causes (4) disease burden of related causes. All across the country, solid fuel use decreased from 5.26% in 1990 to 0.15% in 2013. The drastic reduction of solid fuel use leaded to DALYs attributable to HAP fell by 97.8% (95% uncertainty interval 97.7-98.0%) from 87,433 (51072-144303) in 1990 to 1889 (1016-3247) in 2013. Proportion of YLLs in DALYs from HAP decreased from 95.7% in 1990 to 86.6% in 2013. Contribution of causes in the attributable DALYs was variable during the study period and in 2013 was in the following order: ischemic heart disease for 43.4%, chronic obstructive pulmonary disease for 24.7%, hemorrhagic stroke for 9.7%, lower respiratory infections for 9.3%, ischemic stroke for 7.8%, lung cancer for 3.4% and cataract for 1.8%. Based on the Gini coefficient, the spatial inequality of the disease burden from HAP increased during the study period. The remained burden of disease was relatively scarce and it mainly occurred in seven southern provinces. Further reduction of the disease burden from HAP as well as compensation of the increasing spatial inequality in Iran could be attained through an especial plan for providing cleaner fuels in the southern provinces. Copyright © 2017 Elsevier Inc. All rights reserved.

The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors.

PubMed

Thayer, Julian F; Yamamoto, Shelby S; Brosschot, Jos F

2010-05-28

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The understanding of the risk factors for CVD may yield important insights into the prevention, etiology, course, and treatment of this major public health concern. Autonomic imbalance, characterized by a hyperactive sympathetic system and a hypoactive parasympathetic system, is associated with various pathological conditions. Over time, excessive energy demands on the system can lead to premature aging and diseases. Therefore, autonomic imbalance may be a final common pathway to increased morbidity and mortality from a host of conditions and diseases, including cardiovascular disease. Heart rate variability (HRV) may be used to assess autonomic imbalances, diseases and mortality. Parasympathetic activity and HRV have been associated with a wide range of conditions including CVD. Here we review the evidence linking HRV to established and emerging modifiable and non-modifiable CVD risk factors such as hypertension, obesity, family history and work stress. Substantial evidence exists to support the notion that decreased HRV precedes the development of a number of risk factors and that lowering risk profiles is associated with increased HRV. We close with a suggestion that a model of autonomic imbalance may provide a unifying framework within which to investigate the impact of risk factors, including psychosocial factors and work stress, on cardiovascular disease. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Retinal vascular abnormalities and dragged maculae in a carrier with a new NDP mutation (c.268delC) that caused severe Norrie disease in the proband.

PubMed

Lin, Phoebe; Shankar, Suma P; Duncan, Jacque; Slavotinek, Anne; Stone, Edwin M; Rutar, Tina

2010-02-01

Norrie disease (ND) is caused by mutations in the ND pseudoglioma (NDP) gene (MIM 300658) located at chromosome Xp11.4-p11.3. ND is characterized by abnormal retinal vascular development and vitreoretinal disorganization presenting at birth. Systemic manifestations include sensorineural deafness, progressive mental disorder, behavioral and psychological problems, growth failure, and seizures. Other vitreoretinopathies that are associated with NDP gene mutations include X-linked familial exudative vitreoretinopathy, Coats disease, persistent fetal vasculature, and retinopathy of prematurity. Phenotypic variability associated with NDP gene mutations has been well documented in affected male patients. However, there are limited data on signs in female carriers, with mild peripheral retinal abnormalities reported in both carrier and noncarrier females of families with NDP gene mutations. Here, we report a family harboring a single base-pair deletion, c.268delC, in the NDP gene causing a severe ND phenotype in the male proband and peripheral retinal vascular abnormalities with dragged maculae similar to those observed in familial exudative vitreoretinopathy in his carrier mother. Copyright (c) 2010 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

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.

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.

Identification and prevalence of coral diseases on three Western Indian Ocean coral reefs.

PubMed

Séré, Mathieu G; Chabanet, Pascale; Turquet, Jean; Quod, Jean-Pascal; Schleyer, Michael H

2015-06-03

Coral diseases have caused a substantial decline in the biodiversity and abundance of reef-building corals. To date, more than 30 distinct diseases of scleractinian corals have been reported, which cause progressive tissue loss and/or affect coral growth, reproductive capacity, recruitment, species diversity and the abundance of reef-associated organisms. While coral disease research has increased over the last 4 decades, very little is known about coral diseases in the Western Indian Ocean. Surveys conducted at multiple sites in Reunion, South Africa and Mayotte between August 2010 and June 2012 revealed the presence of 6 main coral diseases: black band disease (BBD), white syndrome (WS), pink line syndrome (PLS), growth anomalies (GA), skeleton eroding band (SEB) and Porites white patch syndrome (PWPS). Overall, disease prevalence was higher in Reunion (7.5 ± 2.2%; mean ± SE) compared to South Africa (3.9 ± 0.8%) and Mayotte (2.7 ± 0.3%). Across locations, Acropora and Porites were the genera most susceptible to disease. Spatial variability was detected in both Reunion and South Africa, with BBD and WS more prevalent on shallow than deep reefs. There was also evidence of seasonality in 2 diseases: the prevalence of BBD and WS was higher in summer than winter. This was the first study to investigate the ecology of coral diseases, providing both qualitative and quantitative data, on Western Indian Ocean reefs, and surveys should be expanded to confirm these patterns.

[Cause of mortality in schizophrenic patients: prospective study of years of a cohort of 150 chronic schizophrenic patients].

PubMed

Bralet, M C; Yon, V; Loas, G; Noisette, C

2000-01-01

Overmortality in schizophrenic patients in comparison to the reference population has been found. At the present time this over mortality is mainly due to suicide or certain natural causes such as respiratory, cardio-vascular and cerebro-vascular diseases. In France there are not psychiatric cas registers that could allow us to study the mortality of psychiatric patients. The aim of the study was first to determine the standardized mortality ratio (SMR) in a group of 150 chronic schizophrenics followed during 8 years and secondly to detect the variables that could predict this mortality. The subjects filled out the RDC criteria for definite chronic schizophrenia and were included from 1991 to 1995. The subjects were inpatients or outpatients and their evaluation was made by psychiatrist. The subjects were selected from the different departments of two psychiatric hospitals corresponding to two French geographic areas (the Somme and Oise, two French "département"). At the initial assessment socio-demographic, clinical and psychometrical variables were collected: sex, age, educative level, number of hospitalizations, mean duration of the illness, scores on the Physical Anhedonia Scale, Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS). For the BPRS and PANSS, negative, positive and general subscales were extracted. In May 1999 all the subjects were contacted in order to know if they are alive or not and if they are death to know the date and the causes of their death. For the subjects that were still alive we used either direct assessment by interview of their psychiatrist or general practioner or indirect assessment by interview of their family. For the deceased subjects, we obtained informations about the date and the causes of the death by their psychiatrist or general practioner. If the patients were lost sight of we send a letter to the city of their place of birth in order to know if they are alive or not and if they are dead to know the date of their death. Moreover demographic data concerning the French and the Somme populations as well as the corresponding data concerning the mortality according to age and gender were obtained. A comparison of global mortality between patients and the French general or the Somme populations was made by the SMR. Moreover the deceased subjects and the survivors were compared by unidimensional statistical tests (chi 2 analyses for qualitative variables or Student's t test for quantitative variables) for the sociodemographic, clinical or psychometric variables. For each significant difference at p level < or = 0.05, the corresponding variable was retained for a multivariate step by step discriminant analysis. We found 13 deaths (10 males, 3 females): 3 suicides, 3 cardiac diseases, 2 cancers, 1 respiratory disease, 1 car crash, 1 homicide, 1 infectious disease, 1 respiratory arrest. The mortality rate (without correction for age) were 1.08% for both sexes, 1.44% and 0.6% for males and females respectively. The mortality rates (corrected for age) were 2.47% in our cohort and 0.988% in the Somme population. The corresponding SMR was 2.5. (chi 2 = 3.15, df = 1, p < 0.01). The overmortality was found only for males (chi 2 = 2.57, df = 1, p < 0.01) and not for females (chi 2 = 0.034, df = 1, p > 0.05). Concerning the comparisons between the deceased subjects and the survivors, there were five significant differences: gender, age, duration of the illness, neuroleptic dosage, negative symptoms (BPRS negative subscale). The deceased subjects were older, there was more men, the duration of the illness and the neuroleptic dosage were higher and the BPRS negative subscale was lower. These five variables were introduced in the discriminant analysis to explore notably their respecting weight. The corresponding power of the five variables were in decreasing order: neuroleptic dosage, negative symptoms, age, gender, duration of the illness. Our study confirm the overmortality in schizophrenic patients, this overmortality was especially explained by natural and non natural causes of death. The overmortality concerned only schizophrenic males patients whereas schizophrenic females did not have an overmortality. This negative result could be explain by a bias selection, the males being overrepresented in our cohort. Among the variables that were linked to the overmortality, the low level of negative symptomatology confirmed previous studies that have shown a low suicide rate in deficit schizophrenic. Moreover a high level of positive symptomatology could lead to high risk behaviors (suicide attempts, sexual disinhibition...). The neuroleptic dosage was the variable whom discriminate power was the highest. At least two explanations can be proposed. (ABSTRACT TRUNCATED)

[Myotonic dystrophy - a new insight into a well-known disease].

PubMed

Lusakowska, Anna; Sułek-Piatkowska, Anna

2010-01-01

Myotonic dystrophy (DM), the most common dystrophy in adults, is an autosomal dominant disease characterized by a variety of multisystemic features. Two genetically distinct forms of DM are identified - type 1 (DM1), the classic form first described by Steinert, and type 2 (DM2), identified by Ricker. DM1 is caused by trinucleotide expansion of CTG in the myotonic dystrophy protein kinase gene, whereas in DM2 the expansion of tetranucleotide repeats (CCTG) in the zinc finger protein 9 gene was identified. Both mutations are dynamic and are located in non-coding parts of the genes. Phenotype variability of DM1 and DM2 is caused by a molecular mechanism due to mutated RNA toxicity. This paper reviews the clinical features of both types of myotonic dystrophies and summarizes current views on pathogenesis of myotonic dystrophy.

Deciphering Suicide and Other Manners of Death Associated with Drug Intoxication: A Centers for Disease Control and Prevention Consultation Meeting Summary.

PubMed

Stone, Deborah M; Holland, Kristin M; Bartholow, Brad; E Logan, Joseph; LiKamWa McIntosh, Wendy; Trudeau, Aimee; Rockett, Ian R H

2017-08-01

Manner of death (MOD) classification (i.e., natural, accident, suicide, homicide, or undetermined cause) affects mortality surveillance and public health research, policy, and practice. Determination of MOD in deaths caused by drug intoxication is challenging, with marked variability across states. The Centers for Disease Control and Prevention hosted a multidisciplinary meeting to discuss drug intoxication deaths as they relate to suicide and other MOD. The meeting objectives were to identify individual-level, system-level, and place-based factors affecting MOD classification and identify potential solutions to classification barriers. Suggested strategies included improved standardization in death scene investigation, toxicology, and autopsy practice; greater accountability; and creation of job aids for investigators. Continued collaboration and coordination of activities are needed among stakeholders to affect prevention efforts.

Variable Effects of Autophagy Induction by Trehalose on Herpesviruses Depending on Conditions of Infection

PubMed Central

Meier, Jeffery L.; Grose, Charles

2017-01-01

Trehalose is a non-reducing sugar formed from two glucose units. Trehalose induces abundant autophagy in cultured cells and also reduces the rate of aggregation of the huntingtin protein in the animal model of Huntington disease, a chronic neurological disease in humans. The mechanism of this effect on autophagy is now known to be caused by starvation secondary to inhibition of a family of glucose transporters known as the solute carrier 2 or the glucose transporter family. Variable effects of trehalose treatment have been observed during infections with two herpesviruses—human cytomegalovirus and varicella-zoster virus. The reasons for differing results have now been delineated. These differences are caused by two variables in conditions of infection: timing of addition of trehalose and type of inoculum (cell-free virus vs. infected cells). When monolayers pretreated with trehalose were inoculated with cell-free virus, there was a decline in virus spread by as much as 93 percent when compared with untreated monolayers. However, when monolayers were inoculated with infected cells rather than cell-free virus, there was no decline in virus spread. These results demonstrated that the effect of trehalose was limited to monolayers that were starved when inoculated with cell-free virus. In contrast, sufficient virus was already present in infected cell inocula so as to minimize any inhibitory effect of a starved monolayer. These results also showed that trehalose did not specifically inhibit a herpesvirus; rather, addition of trehalose to cell culture media altered the intracellular environment. PMID:28356891

Variable Effects of Autophagy Induction by Trehalose on Herpesviruses Depending on Conditions of Infection.

PubMed

Meier, Jeffery L; Grose, Charles

2017-03-01

Trehalose is a non-reducing sugar formed from two glucose units. Trehalose induces abundant autophagy in cultured cells and also reduces the rate of aggregation of the huntingtin protein in the animal model of Huntington disease, a chronic neurological disease in humans. The mechanism of this effect on autophagy is now known to be caused by starvation secondary to inhibition of a family of glucose transporters known as the solute carrier 2 or the glucose transporter family. Variable effects of trehalose treatment have been observed during infections with two herpesviruses-human cytomegalovirus and varicella-zoster virus. The reasons for differing results have now been delineated. These differences are caused by two variables in conditions of infection: timing of addition of trehalose and type of inoculum (cell-free virus vs. infected cells). When monolayers pretreated with trehalose were inoculated with cell-free virus, there was a decline in virus spread by as much as 93 percent when compared with untreated monolayers. However, when monolayers were inoculated with infected cells rather than cell-free virus, there was no decline in virus spread. These results demonstrated that the effect of trehalose was limited to monolayers that were starved when inoculated with cell-free virus. In contrast, sufficient virus was already present in infected cell inocula so as to minimize any inhibitory effect of a starved monolayer. These results also showed that trehalose did not specifically inhibit a herpesvirus; rather, addition of trehalose to cell culture media altered the intracellular environment.

Vesicular erythema migrans: an atypical and easily misdiagnosed form of Lyme disease.

PubMed

Mazori, Daniel R; Orme, Charisse M; Mir, Adnan; Meehan, Shane A; Neimann, Andrea L

2015-08-15

Erythema migrans is the initial sign in the majority of patients infected with Borrelia, the genus of spirochetes that causes Lyme disease. Early identification and treatment decrease the risk of progression to later stages of disease. Although a "bull's eye" appearance owing to lesional clearing is considered classic for erythema migrans, this feature is surprisingly often lacking among patients in the United States. Furthermore, cutaneous Lyme disease can exhibit a wide range of morphologic variability in a minority of patients. Herein, we describe the case of a patient with Lyme disease in which the presence of atypical vesicular features, in conjunction with the initial absence of clearing, resulted in multiple misdiagnoses and delayed treatment. We also review the literature on the epidemiology and management of erythema migrans for cases in which the diagnosis may pose a challenge.

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.

MEG connectivity analysis in patients with Alzheimer's disease using cross mutual information and spectral coherence.

PubMed

Alonso, Joan Francesc; Poza, Jesús; Mañanas, Miguel Angel; Romero, Sergio; Fernández, Alberto; Hornero, Roberto

2011-01-01

Alzheimer's disease (AD) is an irreversible brain disorder which represents the most common form of dementia in western countries. An early and accurate diagnosis of AD would enable to develop new strategies for managing the disease; however, nowadays there is no single test that can accurately predict the development of AD. In this sense, only a few studies have focused on the magnetoencephalographic (MEG) AD connectivity patterns. This study compares brain connectivity in terms of linear and nonlinear couplings by means of spectral coherence and cross mutual information function (CMIF), respectively. The variables defined from these functions provide statistically significant differences (p < 0.05) between AD patients and control subjects, especially the variables obtained from CMIF. The results suggest that AD is characterized by both decreases and increases of functional couplings in different frequency bands as well as by an increase in regularity, that is, more evident statistical deterministic relationships in AD patients' MEG connectivity. The significant differences obtained indicate that AD could disturb brain interactions causing abnormal brain connectivity and operation. Furthermore, the combination of coherence and CMIF features to perform a diagnostic test based on logistic regression improved the tests based on individual variables for its robustness.

Variables and Strategies in Development of Therapeutic Post-Transcriptional Gene Silencing Agents

PubMed Central

Sullivan, Jack M.; Yau, Edwin H.; Kolniak, Tiffany A.; Sheflin, Lowell G.; Taggart, R. Thomas; Abdelmaksoud, Heba E.

2011-01-01

Post-transcriptional gene silencing (PTGS) agents such as ribozymes, RNAi and antisense have substantial potential for gene therapy of human retinal degenerations. These technologies are used to knockdown a specific target RNA and its cognate protein. The disease target mRNA may be a mutant mRNA causing an autosomal dominant retinal degeneration or a normal mRNA that is overexpressed in certain diseases. All PTGS technologies depend upon the initial critical annealing event of the PTGS ligand to the target RNA. This event requires that the PTGS agent is in a conformational state able to support hybridization and that the target have a large and accessible single-stranded platform to allow rapid annealing, although such platforms are rare. We address the biocomplexity that currently limits PTGS therapeutic development with particular emphasis on biophysical variables that influence cellular performance. We address the different strategies that can be used for development of PTGS agents intended for therapeutic translation. These issues apply generally to the development of PTGS agents for retinal, ocular, or systemic diseases. This review should assist the interested reader to rapidly appreciate critical variables in PTGS development and facilitate initial design and testing of such agents against new targets of clinical interest. PMID:21785698

Treating cardiovascular disease in women.

PubMed

Taggu, Wasing; Lloyd, Guy

2007-12-01

Cardiovascular disease (CVD) is the most common cause of death in women but some of the challenges of management differ from those in men. This article addresses the gender-specific issues of cardiovascular management, with emphasis on ischaemic heart disease and modification of coronary risk factors. Women with ischaemic heart disease present later than men, and are therefore older and more likely to suffer from co-morbidities such as diabetes and hypertension. Proven CVD risk factors in women can be divided into those that are modifiable and those that are non-modifiable. The former include diabetes, dyslipidaemia, hypertension, smoking, obesity, sedentary lifestyle and poor nutrition; the latter include family history of heart disease and older age at presentation. It is this difference in age and general health that explains much of the variability in response to treatment. Pharmacotherapy, percutaneous intervention, surgical revascularization, and cardiac rehabilitation and disease prevention are discussed.

Behavioural prevention of ischemic heart disease.

PubMed Central

Hartman, L. M.

1978-01-01

Heart disease continues to be a major cause of disablement and death in Canada. Elevated serum cholesterol concentrations, hypertension and cigarette smoking are among the standard risk factors associated with ischemic heart disease. Research attention has also been directed at the role of behavioural factors in the development of atherosclerosis and myocardial infarction. Experimental findings support a conceptual approach to the interplay of psychologic stress, the type A "coronary"-prone behaviour pattern and pathophysiologic mechanisms that have been implicated in the development of coronary artery disease. It is concluded that type A behaviour and stress contribute substantially to the pathogenesis of cardiovascular disease. However, assessment of the manner in which these two variables influence the pathophysiology of ischemic heart disease requires further research, with systematic examination of physiologic and biochemical processes. Potential strategies for modifying type A behaviour are reviewed. However, unequivocal support for the preventive efficacy of behavioural approaches must await future research. PMID:361191

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...

[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.

Is the common cold a clinical entity or a cultural concept?

PubMed

Eccles, R

2013-03-01

Common cold is the most common infectious disease of mankind and the term is widely used in the clinical literature as though it were a defined clinical syndrome. Clinical studies on this syndrome often use elaborate symptom scoring systems to diagnose a common cold. The symptom scores are based on a study conducted over 50 years ago to retrospectively diagnose experimental cold and this method cannot be applied to diagnosis of common cold in the community. Diagnosis of the common cold by virology is not feasible because of the number of viruses and the variability in the disease states caused by the viruses. Because of the familiarity of subjects with common cold and the variability in symptomatology it seems a more reasonable approach to use self-diagnosis of common cold for clinical research studies and accept that the common cold is a cultural concept and not a clinical entity.

Remotely sensed vegetation moisture as explanatory variable of Lyme borreliosis incidence

NASA Astrophysics Data System (ADS)

Barrios, J. M.; Verstraeten, W. W.; Maes, P.; Clement, J.; Aerts, J. M.; Farifteh, J.; Lagrou, K.; Van Ranst, M.; Coppin, P.

2012-08-01

The strong correlation between environmental conditions and abundance and spatial spread of the tick Ixodes ricinus is widely documented. I. ricinus is in Europe the main vector of the bacterium Borrelia burgdorferi, the pathogen causing Lyme borreliosis (LB). Humidity in vegetated systems is a major factor in tick ecology and its effects might translate into disease incidence in humans. Time series of two remotely sensed indices with sensitivity to vegetation greenness and moisture were tested as explanatory variables of LB incidence. Wavelet-based multiresolution analysis allowed the examination of these signals at different temporal scales in study sites in Belgium, where increases in LB incidence were reported in recent years. The analysis showed the potential of the tested indices for disease monitoring, the usefulness of analyzing the signal in different time frames and the importance of local characteristics of the study area for the selection of the vegetation index.

Food hygiene practices and its associated factors among model and non model households in Abobo district, southwestern Ethiopia: Comparative cross-sectional study.

PubMed

Okugn, Akoma; Woldeyohannes, Demelash

2018-01-01

In developing country most of human infectious diseases are caused by eating contaminated food. Estimated nine out ten of the diarrheal disease is attributable to the environment and associated with risk factors of poor food hygiene practice. Understanding the risk of eating unsafe food is the major concern to prevent and control food borne diseases. The main goal of this study was to assessing food hygiene practices and its associated factors among model and non model households at Abobo district. This study was conducted from 18 October 2013 to 13 June 2014. A community-based comparative cross-sectional study design was used. Pretested structured questionnaire was used to collect data. A total of 1247 households (417 model and 830 non model households) were included in the study from Abobo district. Bivariate and multivariate logistic regression analysis was used to identify factors associated with outcome variable. The study revealed that good food hygiene practice was 51%, of which 79% were model and 36.70% were non model households. Type of household [AOR: 2.07, 95% CI: (1.32-3.39)], sex of household head [AOR: 1.63, 95% CI: (1.06-2.48)], Availability of liquid wastes disposal pit [AOR: 2.23, 95% CI: (1.39,3.63)], Knowledge of liquid waste to cause diseases [AOR: 1.95, 95% (1.23,3.08)], and availability of functional hand washing facility [AOR: 3.61, 95% CI: (1.86-7.02)] were the factors associated with food handling practices. This study revealed that good food handling practice is low among model and non model households. While type of household (model versus non model households), sex, knowledge of solid waste to cause diseases, availability of functional hand washing facility, and availability of liquid wastes disposal pit were the factors associated with outcome variable. Health extension workers should play a great role in educating households regarding food hygiene practices to improve their knowledge and practices of the food hygiene.

Avian malaria in a boreal resident species: long-term temporal variability, and increased prevalence in birds with avian keratin disorder

USGS Publications Warehouse

Wilkinson, Laura C.; Handel, Colleen M.; Van Hemert, Caroline R.; Loiseau, Claire; Sehgal, Ravinder N. M.

2016-01-01

The prevalence of vector-borne parasitic diseases is widely influenced by biological and ecological factors. Environmental conditions such as temperature and precipitation can have a marked effect on haemosporidian parasites (Plasmodium spp.) that cause malaria and those that cause other malaria-like diseases in birds. However, there have been few long-term studies monitoring haemosporidian infections in birds in northern latitudes, where weather conditions can be highly variable and the effects of climate change are becoming more pronounced. We used molecular methods to screen more than 2,000 blood samples collected from black-capped chickadees (Poecile atricapillus), a resident passerine bird. Samples were collected over a 10 year period, mostly during the non-breeding season, at seven sites in Alaska, USA. We tested for associations between Plasmodium prevalence and local environmental conditions including temperature, precipitation, site, year and season. We also evaluated the relationship between parasite prevalence and individual host factors of age, sex and presence or absence of avian keratin disorder. This disease, which causes accelerated keratin growth in the beak, provided a natural study system in which to test the interaction between disease state and malaria prevalence. Prevalence of Plasmodium infection varied by year, site, age and individual disease status but there was no support for an effect of sex or seasonal period. Significantly, birds with avian keratin disorder were 2.6 times more likely to be infected by Plasmodium than birds without the disorder. Interannual variation in the prevalence of Plasmodium infection at different sites was positively correlated with summer temperatures at the local but not statewide scale. Sequence analysis of the parasite cytochrome b gene revealed a single Plasmodiumspp. lineage, P43. Our results demonstrate associations between prevalence of avian malaria and a variety of biological and ecological factors. These results also provide important baseline data that will be informative for predicting future changes inPlasmodium prevalence in the subarctic.

Phenotypic variability in monozygotic twins with neurofibromatosis 2

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

Baser, M.E.; Ragge, N.K.; Riccardi, V.M.

Mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene on chromosome 22q12 cause a clinically variable autosomal dominant syndrome characterized by bilateral vestibular schwannomas (VSs), other nervous system tumors, and early onset lenticular cataracts. We studied three pairs of monozygotic (MZ) twins with NF2, all with bilateral VSs, to separate genetic from nongenetic causes of clinical variability. The evaluation included gadolinium-enhanced high-resolution magnetic resonance imaging of the head and spine, neuro-ophthalmic examination with slit lamp, physical examination, and zygosity testing with microsatellite markers. Each MZ pair was concordant for general phenotypic subtype (mild or severe) and often for the affectedmore » organ systems. However, the MZ pairs were discordant for some features of disease presentation or progression. For example, all three pairs were discordant for presence or type of associated cranial tumors. We hypothesize that phenotypic differences between NF2 MZ twins are at least partly due to stochastic processes, such as the loss of the second NF2 allele or alleles of other genes. 42 refs., 1 tab.« less

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

Etiological Theories of Adolescent Idiopathic Scoliosis: Past and Present

PubMed Central

Fadzan, Maja; Bettany-Saltikov, Josette

2017-01-01

Adolescent idiopathic scoliosis is one of the most common spinal deformities, yet its cause is unknown. Various theories look to biomechanical, neuromuscular, genetic, and environmental origins, yet our understanding of scoliosis etiology is still limited. Determining the cause of a disease is crucial to developing the most effective treatment. Associations made with scoliosis do not necessarily point to causality, and it is difficult to determine whether said associations are primary (playing a role in development) or secondary (develop as a result of scoliosis). Scoliosis is a complex condition with highly variable expression, even among family members, and likely has many causes. These causes could be similar among homogenous groups of AIS patients, or they could be individual. Here, we review the most prevalent theories of scoliosis etiology and recent trends in research. PMID:29399224

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

Causes of Death among People Living with AIDS in the Pre- and Post-HAART Eras in the City of São Paulo, Brazil

PubMed Central

Domingues, Carmen-Silvia Bruniera; Waldman, Eliseu Alves

2014-01-01

Objective We examine the trend in causes of death among people living with AIDS in the city of São Paulo, Brazil, in the periods before and after the introduction of highly active antiretroviral therapy (HAART), and we investigate potential disparities across districts of residence. Methods Descriptive study of three periods: pre-HAART (1991–1996); early post-HAART (1997–1999); and late post-HAART (2000–2006). The data source was the São Paulo State STD/AIDS Program and São Paulo State Data Analysis Foundation. Causes of death were classified by the ICD-9 (1991–1995) and ICD-10 (1996–2006). We estimated age-adjusted mortality rates for leading underlying causes of death and described underlying and associated causes of death according to sociodemographic characteristics and area of residence. We used Pearson's chi-square test or Fisher's exact test to compare categorical variables. Areas of residence were categorized using a socioeconomic index. To analyze trends we apply generalized linear model with Poisson regression. Results We evaluated 32,808 AIDS-related deaths. Between the pre- and late post-HAART periods, the proportion of deaths whose underlying causes were non-AIDS-related diseases increased from 0.2% to 9.6% (p<0.001): from 0.01% to 1.67% (p<0.001) for cardiovascular diseases; 0.01% to 1.62% (p<0.001) for bacterial/unspecified pneumonia; and 0.03% to 1.46% (p<0.001) for non-AIDS-defining cancers. In the late post-HAART period, the most common associated causes of death were bacterial/unspecified pneumonia (35.94%), septicemia (33.46%), cardiovascular diseases (10.11%) and liver diseases (8.0%); and common underlying causes, besides AIDS disease, included non-AIDS-defining cancers in high-income areas, cardiovascular diseases in middle-income areas and assault in low-income areas. Conclusions The introduction of HAART has shifted the mortality profile away from AIDS-related conditions, suggesting changes in the pattern of morbidity, but heterogeneously according to area of residence. There is a need for public policies aimed at adapting health care services to address the new scenario. PMID:25500837

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.

Mapping and predicting mortality from systemic sclerosis.

PubMed

Elhai, Muriel; Meune, Christophe; Boubaya, Marouane; Avouac, Jérôme; Hachulla, Eric; Balbir-Gurman, Alexandra; Riemekasten, Gabriela; Airò, Paolo; Joven, Beatriz; Vettori, Serena; Cozzi, Franco; Ullman, Susanne; Czirják, László; Tikly, Mohammed; Müller-Ladner, Ulf; Caramaschi, Paola; Distler, Oliver; Iannone, Florenzo; Ananieva, Lidia P; Hesselstrand, Roger; Becvar, Radim; Gabrielli, Armando; Damjanov, Nemanja; Salvador, Maria J; Riccieri, Valeria; Mihai, Carina; Szücs, Gabriella; Walker, Ulrich A; Hunzelmann, Nicolas; Martinovic, Duska; Smith, Vanessa; Müller, Carolina de Souza; Montecucco, Carlo Maurizio; Opris, Daniela; Ingegnoli, Francesca; Vlachoyiannopoulos, Panayiotis G; Stamenkovic, Bojana; Rosato, Edoardo; Heitmann, Stefan; Distler, Jörg H W; Zenone, Thierry; Seidel, Matthias; Vacca, Alessandra; Langhe, Ellen De; Novak, Srdan; Cutolo, Maurizio; Mouthon, Luc; Henes, Jörg; Chizzolini, Carlo; Mühlen, Carlos Alberto von; Solanki, Kamal; Rednic, Simona; Stamp, Lisa; Anic, Branimir; Santamaria, Vera Ortiz; De Santis, Maria; Yavuz, Sule; Sifuentes-Giraldo, Walter Alberto; Chatelus, Emmanuel; Stork, Jiri; Laar, Jacob van; Loyo, Esthela; García de la Peña Lefebvre, Paloma; Eyerich, Kilian; Cosentino, Vanesa; Alegre-Sancho, Juan Jose; Kowal-Bielecka, Otylia; Rey, Grégoire; Matucci-Cerinic, Marco; Allanore, Yannick

2017-11-01

To determine the causes of death and risk factors in systemic sclerosis (SSc). Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

Genotype and phenotype spectrum of NRAS germline variants.

PubMed

Altmüller, Franziska; Lissewski, Christina; Bertola, Debora; Flex, Elisabetta; Stark, Zornitza; Spranger, Stephanie; Baynam, Gareth; Buscarilli, Michelle; Dyack, Sarah; Gillis, Jane; Yntema, Helger G; Pantaleoni, Francesca; van Loon, Rosa LE; MacKay, Sara; Mina, Kym; Schanze, Ina; Tan, Tiong Yang; Walsh, Maie; White, Susan M; Niewisch, Marena R; García-Miñaúr, Sixto; Plaza, Diego; Ahmadian, Mohammad Reza; Cavé, Hélène; Tartaglia, Marco; Zenker, Martin

2017-06-01

RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly conserved RAS-MAPK signalling pathway that lead to dysregulation of cell signal transmission. Germline changes in the genes encoding members of the RAS subfamily of GTPases are rare and associated with variable phenotypes of the RASopathy spectrum, ranging from Costello syndrome (HRAS variants) to Noonan and Cardiofaciocutaneous syndromes (KRAS variants). A small number of RASopathy cases with disease-causing germline NRAS alterations have been reported. Affected individuals exhibited features fitting Noonan syndrome, and the observed germline variants differed from the typical oncogenic NRAS changes occurring as somatic events in tumours. Here we describe 19 new cases with RASopathy due to disease-causing variants in NRAS. Importantly, four of them harbored missense changes affecting Gly12, which was previously described to occur exclusively in cancer. The phenotype in our cohort was variable but well within the RASopathy spectrum. Further, one of the patients (c.35G>A; p.(Gly12Asp)) had a myeloproliferative disorder, and one subject (c.34G>C; p.(Gly12Arg)) exhibited an uncharacterized brain tumour. With this report, we expand the genotype and phenotype spectrum of RASopathy-associated germline NRAS variants and provide evidence that NRAS variants do not spare the cancer-associated mutation hotspots.

Assessing the Role of Climate Variability on Liver Fluke Risk in the UK Through Mechanistic Hydro-Epidemiological Modelling

NASA Astrophysics Data System (ADS)

Beltrame, L.; Dunne, T.; Rose, H.; Walker, J.; Morgan, E.; Vickerman, P.; Wagener, T.

2016-12-01

Liver fluke is a flatworm parasite infecting grazing animals worldwide. In the UK, it causes considerable production losses to cattle and sheep industries and costs farmers millions of pounds each year due to reduced growth rates and lower milk yields. Large part of the parasite life-cycle takes place outside of the host, with its survival and development strongly controlled by climatic and hydrologic conditions. Evidence of climate-driven changes in the distribution and seasonality of fluke disease already exists, as the infection is increasingly expanding to new areas and becoming a year-round problem. Therefore, it is crucial to assess current and potential future impacts of climate variability on the disease to guide interventions at the farm scale and mitigate risk. Climate-based fluke risk models have been available since the 1950s, however, they are based on empirical relationships derived between historical climate and incidence data, and thus are unlikely to be robust for simulating risk under changing conditions. Moreover, they are not dynamic, but estimate risk over large regions in the UK based on monthly average climate conditions, so they do not allow investigating the effects of climate variability for supporting farmers' decisions. In this study, we introduce a mechanistic model for fluke, which represents habitat suitability for disease development at 25m resolution with a daily time step, explicitly linking the parasite life-cycle to key hydro-climate conditions. The model is used on a case study in the UK and sensitivity analysis is performed to better understand the role of climate variability on the space-time dynamics of the disease, while explicitly accounting for uncertainties. Comparisons are presented with experts' knowledge and a widely used empirical model.

Remotely Sensed Environmental Conditions and Malaria Mortality in Three Malaria Endemic Regions in Western Kenya.

PubMed

Sewe, Maquins Odhiambo; Ahlm, Clas; Rocklöv, Joacim

2016-01-01

Malaria is an important cause of morbidity and mortality in malaria endemic countries. The malaria mosquito vectors depend on environmental conditions, such as temperature and rainfall, for reproduction and survival. To investigate the potential for weather driven early warning systems to prevent disease occurrence, the disease relationship to weather conditions need to be carefully investigated. Where meteorological observations are scarce, satellite derived products provide new opportunities to study the disease patterns depending on remotely sensed variables. In this study, we explored the lagged association of Normalized Difference Vegetation Index (NVDI), day Land Surface Temperature (LST) and precipitation on malaria mortality in three areas in Western Kenya. The lagged effect of each environmental variable on weekly malaria mortality was modeled using a Distributed Lag Non Linear Modeling approach. For each variable we constructed a natural spline basis with 3 degrees of freedom for both the lag dimension and the variable. Lag periods up to 12 weeks were considered. The effect of day LST varied between the areas with longer lags. In all the three areas, malaria mortality was associated with precipitation. The risk increased with increasing weekly total precipitation above 20 mm and peaking at 80 mm. The NDVI threshold for increased mortality risk was between 0.3 and 0.4 at shorter lags. This study identified lag patterns and association of remote- sensing environmental factors and malaria mortality in three malaria endemic regions in Western Kenya. Our results show that rainfall has the most consistent predictive pattern to malaria transmission in the endemic study area. Results highlight a potential for development of locally based early warning forecasts that could potentially reduce the disease burden by enabling timely control actions.

Association of Proteinuria with Race, Cause of Chronic Kidney Disease, and Glomerular Filtration Rate in the Chronic Kidney Disease in Children Study

PubMed Central

Wong, Craig S.; Pierce, Christopher B.; Cole, Stephen R.; Warady, Bradley A.; Mak, Robert H.K.; Benador, Nadine M.; Kaskel, Fredrick; Furth, Susan L.; Schwartz, George J.

2009-01-01

Background and objectives: Proteinuria is associated with chronic kidney disease (CKD), and heavy proteinuria predicts a rapid decline in kidney function. However, the epidemiologic distribution of this important biomarker study is not well described in the pediatric CKD population. Design, setting, participants & measurements: This cross-sectional study of North American children with CKD examined the association of proteinuria among the baseline clinical variables in the cohort. Urinary protein-to-creatinine ratios (Up/c) were used to measure level of proteinuria. Results: Of the 419 subjects studied, the median GFR as measured by iohexol disappearance (iGFR) was 42 ml/min per 1.73 m2, median duration of CKD was six yr, and glomerular diseases accounted for 22% of the CKD diagnoses. Twenty-four percent of children had normal range (Up/c <0.2), 62% had significant, and 14% had nephrotic-range proteinuria (Up/c >2.0). A decrease in iGFR was associated with an increase in Up/c. At any level of GFR, a higher Up/c was associated with a glomerular cause of CKD and non-Caucasian race. Among subjects with a glomerular cause of CKD, Up/c was lower in subjects reporting utilization of renin-angiotensin system (RAS) antagonists (median Up/c = 0.93) compared with those who did not (median Up/c = 3.78). Conclusions: Proteinuria is associated with level of iGFR, cause of CKD, and race. The longitudinal study design of Chronic Kidney Disease in Children (CKiD) cohort study and the large number of subjects being studied has created an opportunity to better define the association between proteinuria and CKD progression. PMID:19297612

Predictors of long-term mortality following elective endovascular repair of abdominal aortic aneurysms.

PubMed

Marques-Rios, Guilherme; Oliveira-Pinto, José; Mansilha, Armando

2018-05-09

Endovascular aneurysm repair (EVAR) became the preferred modality for abdominal aortic aneurysm (AAA) repair. However, long term survival benefit may sometimes be questionable as many patients would die from other causes rather than aneurysm rupture. It is paramount to identify critical risk factors for late mortality after EVAR to understand its real benefit. The aim of this review is to identify most clinically relevant determinants of late mortality after elective EVAR. English literature was searched to identify publications on long-term predictors of mortality following elective EVAR. A follow-up extending for at least 5 years was the minimum required as inclusion criteria. Primary endpoint was all-cause mortality. We addressed clinical and demographic variables and observe if they had any associations with long-term all-cause mortality following EVAR. Thirteen studies were included describing more than 82306 patients, exploring at least one predictors of long-term mortality. All-cause mortality was associated to age (Hazard Ratio[HR] 1.06-3.34), gender (HR 1.07), aneurysm diameter (HR 1.09-1.64), smoking habits (HR 1.51-1.73), heart failure (HR 1.60-7.34), ischemic heart disease (HR 1.60), peripheral vascular disease (HR 1.30), cerebrovascular disease (HR 1.55), diabetes mellitus (HR 6.35), chronic obstructive pulmonary disease (HR 1.50-2.06) and chronic renal disease (HR 1.90-3.08). Risk factors associated with long-term mortality following elective EVAR remain scarcely published. Several demographic, anatomical, cardiovascular, pulmonary and renal co-morbidities seem to have an association with long-term mortality. Critical scrutiny of clinical patient status remains fundamental for a fair health resources allocation.

Impact of Dietary and Metabolic Risk Factors on Cardiovascular and Diabetes Mortality in South Asia: Analysis From the 2010 Global Burden of Disease Study.

PubMed

Yakoob, Mohammad Y; Micha, Renata; Khatibzadeh, Shahab; Singh, Gitanjali M; Shi, Peilin; Ahsan, Habibul; Balakrishna, Nagalla; Brahmam, Ginnela N V; Chen, Yu; Afshin, Ashkan; Fahimi, Saman; Danaei, Goodarz; Powles, John W; Ezzati, Majid; Mozaffarian, Dariush

2016-12-01

To quantify cardiovascular disease and diabetes deaths attributable to dietary and metabolic risks by country, age, sex, and time in South Asian countries. We used the 2010 Global Burden of Disease national surveys to characterize risk factor levels by age and sex. We derived etiological effects of risk factors-disease endpoints, by age, from meta-analyses. We defined optimal levels. We combined these inputs with cause-specific mortality rates to compute population-attributable fractions as a percentage of total cardiometabolic deaths. Suboptimal diet was the leading cause of cardiometabolic mortality in 4 of 5 countries, with population-attributable fractions from 40.7% (95% uncertainty interval = 37.4, 44.1) in Bangladesh to 56.9% (95% uncertainty interval = 52.4, 61.5) in Pakistan. High systolic blood pressure was the second leading cause, except in Bangladesh, where it superseded suboptimal diet. This was followed in all nations by high fasting plasma glucose, low fruit intake, and low whole grain intake. Other prominent burdens were more variable, such as low intake of vegetables, low omega-3 fats, and high sodium intake in India, Nepal, and Pakistan. Important similarities and differences are evident in cardiometabolic mortality burdens of modifiable dietary and metabolic risks across these countries, informing health policy and program priorities.

The Complexity of Clinical Huntington's Disease: Developments in Molecular Genetics, Neuropathology and Neuroimaging Biomarkers.

PubMed

Tippett, Lynette J; Waldvogel, Henry J; Snell, Russell G; Vonsattel, Jean-Paul; Young, Anne B; Faull, Richard L M

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by extensive neuronal loss in the striatum and cerebral cortex, and a triad of clinical symptoms affecting motor, cognitive/behavioural and mood functioning. The mutation causing HD is an expansion of a CAG tract in exon 1 of the HTT gene. This chapter provides a multifaceted overview of the clinical complexity of HD. We explore recent directions in molecular genetics including the identification of loci that are genetic modifiers of HD that could potentially reveal therapeutic targets beyond the HTT gene transcript and protein. The variability of clinical symptomatology in HD is considered alongside recent findings of variability in cellular and neurochemical changes in the striatum and cerebral cortex in human brain. We review evidence from structural neuroimaging methods of progressive changes of striatum, cerebral cortex and white matter in pre-symptomatic and symptomatic HD, with a particular focus on the potential identification of neuroimaging biomarkers that could be used to test promising disease-specific and modifying treatments. Finally we provide an overview of completed clinical trials in HD and future therapeutic developments.

[Epidemiological situation of the selected infectious diseases in Poland in 1918-1939].

PubMed

Sztuka-Polińska, Urszula

2002-01-01

In Poland, during twenty years between the first and the second world war modern methods and remedies were created and applied to save the society from biological extermination caused by the epidemics of acute infectious diseases that existed in the larger areas of the country and other diseases that could threaten the society when brought from abroad. Poland regained its independence in 1918 as a country completely destroyed by war and encompassed three partitioned sectors that differed in wealth, class consciousness, various infrastructure, legislation, epidemiological situation of infectious diseases and threats spreading from abroad. Infectious diseases such as typhus fever, typhoid fever, cholera, smallpox, dysentery and other diseases spreading by alimentary tracts caused the greatest epidemiological problem. The considerable number of smallpox cases was noted in 1920-1922. In the thirties only individual cases occurred. Since 1934 no fatal cases of smallpox were registered. In 1919, in Poland 219,688 cases and 18,641 typhus fever deaths were registered. Between 1930 and 1939 the annual number of cases ranged from 2000 to 4000. In Poland each year between the first and the second world war typhoid fever was a serious sanitary problem. The largest outbreak of dysentery occurred in Poland in 1920-1921 and comprised 64,000 cases, among them 10,000 deaths. Acute childhood diseases such as scarlet fever and diphtheria were in Poland endemic. Number of registered cases was variable.

What predicts depression in cardiac patients: sociodemographic factors, disease severity or theoretical vulnerabilities?

PubMed

Doyle, F; McGee, H M; Conroy, R M; Delaney, M

2011-05-01

Depression is associated with increased cardiovascular risk in acute coronary syndrome (ACS) patients, but some argue that elevated depression is actually a marker of cardiovascular disease severity. Therefore, disease indices should better predict depression than established theoretical causes of depression (interpersonal life events, reinforcing events, cognitive distortions, type D personality). However, little theory-based research has been conducted in this area. In a cross-sectional design, ACS patients (n = 336) completed questionnaires assessing depression and psychosocial vulnerabilities. Nested logistic regression assessed the relative contribution of demographic or vulnerability factors, or disease indices or vulnerabilities to depression. In multivariate analysis, all vulnerabilities were independent significant predictors of depression (scoring above threshold on any scale, 48%). Demographic variables accounted for <1% of the variance of depression status, with vulnerabilities accounting for significantly more (pseudo R² = 0.16, χ²(change) = 150.9, df = 4, p < 0.001). Disease indices accounted for 7% of the variance in depression (pseudo R² = 0.07, χ² = 137.9, p < 0.001). However, adding the vulnerabilities increased the overall variance explained to 22% (pseudo R² = 0.22, χ² = 58.6, df = 4, p < 0.001). Theoretical vulnerabilities predicted depression status better than did either demographic or disease indices. The presence of these proximal causes of depression suggests that depression in ACS patients is not simply a result of cardiovascular disease severity.

Recommendations for the inclusion of Fabry disease as a rare febrile condition in existing algorithms for fever of unknown origin.

PubMed

Manna, Raffaele; Cauda, Roberto; Feriozzi, Sandro; Gambaro, Giovanni; Gasbarrini, Antonio; Lacombe, Didier; Livneh, Avi; Martini, Alberto; Ozdogan, Huri; Pisani, Antonio; Riccio, Eleonora; Verrecchia, Elena; Dagna, Lorenzo

2017-10-01

Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.

A Cross-Sectional Study of the Prevalence of Gastrointestinal Symptoms and Pathology in Patients With Common Variable Immunodeficiency.

PubMed

Jørgensen, Silje F; Reims, Henrik M; Frydenlund, Didrik; Holm, Kristian; Paulsen, Vemund; Michelsen, Annika E; Jørgensen, Kristin K; Osnes, Liv T; Bratlie, Jorunn; Eide, Tor J; Dahl, Christen P; Holter, Ellen; Tronstad, Rune R; Hanevik, Kurt; Brattbakk, Hans-Richard; Kaveh, Fatemeh; Fiskerstrand, Torunn; Kran, Anne-Marte B; Ueland, Thor; Karlsen, Tom H; Aukrust, Pål; Lundin, Knut E A; Fevang, Børre

2016-10-01

The objective of this study was to study the prevalence of gastrointestinal (GI) symptoms and histopathology in patients with common variable immunodeficiency (CVID) as well as linking the findings to GI infections and markers of systemic immune activation. In this cross-sectional study, we addressed GI symptoms in 103 patients and GI histopathological findings in 53 patients who underwent upper and lower endoscopic examination. The most frequent histopathological findings were linked to GI symptoms, B-cell phenotype, and markers of systemic immune activation (soluble (s)CD14, sCD25, and sCD163). Microarray analysis compared "celiac-like disease" in CVID to celiac disease. Screening for selected bacterial and viral infections in fecal samples and gut mucosal biopsies was performed. The main findings of this study were as follows: most common GI symptoms were bloating (34%), pain (30%), and diarrhea (26%). The most frequent histopathological findings were increased intraepithelial lymphocytes in the descending part of the duodenum, i.e., "celiac-like disease" (46% of patients), decreased numbers of plasma cells in GI tract mucosa (62%), and lymphoid hyperplasia (38%), none of which were associated with GI symptoms. Reduced plasma cells in GI mucosa were associated with B-cell phenotypic characteristics of CVID, and increased serum levels of sCD14 (P=0.025), sCD25 (P=0.01), and sCD163 (P=0.04). Microarray analyses distinguished between CVID patients with "celiac-like disease" and celiac disease. Positive tests for bacterial and viral infections were scarce both in fecal samples and gut mucosal biopsies, including PCR test for norovirus in biopsy specimens (0 positive tests). In conclusion, GI pathology is common in CVID, but does not necessarily cause symptoms. However, reduced plasma cells in GI mucosa were linked to systemic immune activation, "celiac-like disease" in CVID and true celiac disease appear to be different disease entities, as assessed by gene expression, and infections (including norovirus) are rarely a cause of the CVID enteropathy.

Optimism and Cause-Specific Mortality: A Prospective Cohort Study.

PubMed

Kim, Eric S; Hagan, Kaitlin A; Grodstein, Francine; DeMeo, Dawn L; De Vivo, Immaculata; Kubzansky, Laura D

2017-01-01

Growing evidence has linked positive psychological attributes like optimism to a lower risk of poor health outcomes, especially cardiovascular disease. It has been demonstrated in randomized trials that optimism can be learned. If associations between optimism and broader health outcomes are established, it may lead to novel interventions that improve public health and longevity. In the present study, we evaluated the association between optimism and cause-specific mortality in women after considering the role of potential confounding (sociodemographic characteristics, depression) and intermediary (health behaviors, health conditions) variables. We used prospective data from the Nurses' Health Study (n = 70,021). Dispositional optimism was measured in 2004; all-cause and cause-specific mortality rates were assessed from 2006 to 2012. Using Cox proportional hazard models, we found that a higher degree of optimism was associated with a lower mortality risk. After adjustment for sociodemographic confounders, compared with women in the lowest quartile of optimism, women in the highest quartile had a hazard ratio of 0.71 (95% confidence interval: 0.66, 0.76) for all-cause mortality. Adding health behaviors, health conditions, and depression attenuated but did not eliminate the associations (hazard ratio = 0.91, 95% confidence interval: 0.85, 0.97). Associations were maintained for various causes of death, including cancer, heart disease, stroke, respiratory disease, and infection. Given that optimism was associated with numerous causes of mortality, it may provide a valuable target for new research on strategies to improve health. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The association between Darier disease, bipolar disorder, and schizophrenia revisited: a population-based family study.

PubMed

Cederlöf, Martin; Bergen, Sarah E; Långström, Niklas; Larsson, Henrik; Boman, Marcus; Craddock, Nick; Östberg, Per; Lundström, Sebastian; Sjölander, Arvid; Nordlind, Klas; Landén, Mikael; Lichtenstein, Paul

2015-05-01

Darier disease is an autosomal dominant skin disorder caused by mutations in the ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) gene and previously reported to cosegregate with bipolar disorder and schizophrenia in occasional pedigrees. It is, however, unknown whether these associations exist also in the general population, and the objective of this study was to examine this question. We compared a national sample of individuals with Darier disease and their first-degree relatives with matched unexposed individuals from the general population and their first-degree relatives, respectively. To examine risks for bipolar disorder and schizophrenia, risk ratios and 95% confidence intervals (CIs) were estimated using conditional logistic regressions. Individuals with Darier disease had a 4.3 times higher risk of being diagnosed with bipolar disorder (95% CI: 2.6-7.3) and a 2.3 times higher risk of being diagnosed with schizophrenia (95% CI: 1.1-5.2) than matched individuals from the general population. Relatives of individuals with Darier disease had a 1.6 times higher risk of having bipolar disorder (95% CI: 1.1-2.5) than relatives of matched individuals from the general population, but no increased risk of schizophrenia (risk ratio = 0.8, 95% CI: 0.4-1.8). The association between Darier disease and bipolar disorder is manifest also in the population, and our data suggest that genetic variability within the ATP2A2 gene that causes Darier disease also confers susceptibility for bipolar disorder. The Darier-causing mutations merit additional attention in molecular genetic research on bipolar disorder. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic variability of Brazilian isolates of Alternaria alternata detected by AFLP and RAPD techniques

PubMed Central

Dini-Andreote, Francisco; Pietrobon, Vivian Cristina; Andreote, Fernando Dini; Romão, Aline Silva; Spósito, Marcel Bellato; Araújo, Welington Luiz

2009-01-01

The Alternaria brown spot (ABS) is a disease caused in tangerine plants and its hybrids by the fungus Alternaria alternata f. sp. citri which has been found in Brazil since 2001. Due to the recent occurrence in Brazilian orchards, the epidemiology and genetic variability of this pathogen is still an issue to be addressed. Here it is presented a survey about the genetic variability of this fungus by the characterization of twenty four pathogenic isolates of A. alternata f. sp. citri from citrus plants and four endophytic isolates from mango (one Alternaria tenuissima and three Alternaria arborescens). The application of two molecular markers Random Amplified Polymorphic DNA (RAPD) and Amplified Fragment Length Polymorphism (AFLP) had revealed the isolates clustering in distinct groups when fingerprintings were analyzed by Principal Components Analysis (PCA). Despite the better assessment of the genetic variability through the AFLP, significant modifications in clusters components were not observed, and only slight shifts in the positioning of isolates LRS 39/3 and 25M were observed in PCA plots. Furthermore, in both analyses, only the isolates from lemon plants revealed to be clustered, differently from the absence of clustering for other hosts or plant tissues. Summarizing, both RAPD and AFLP analyses were both efficient to detect the genetic variability within the population of the pathogenic fungus Alternaria spp., supplying information on the genetic variability of this species as a basis for further studies aiming the disease control. PMID:24031413

Pediatric genetic disease of the cornea

PubMed Central

Fecarotta, Christopher M.; Huang, Wendy W.

2014-01-01

Our objective is to evaluate the literature regarding selected genetic diseases of the cornea, including megalocornea, keratoglobus, keratoconus, cystinosis, the mucopolysaccharidoses, sclerocornea, Peters' anomaly, familial dysautonomia, and various corneal dystrophies. The transparency of the cornea is a consequence of uniformity in both size and spacing of the collagen lamellae. The cornea's clarity depends on a delicate biochemical and structural balance; consequently, genetic disorders that disrupt either its metabolic or anatomic function can cause opacity and vision loss. Many childhood corneal diseases have a genetic etiology and are associated with known syndromes. Each disorder has unique associated set of possible complications. Prognosis often depends on the extent of opacity and disorganization of the anterior segment. Corneal transplantation has been performed for these disorders with variable success. PMID:27625877

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.

Immunizations for the college student: a campus perspective of an outbreak and national and international considerations.

PubMed

Kumar, Ashir; Murray, Dennis L; Havlichek, Daniel H

2005-02-01

Although vaccine-preventable diseases have declined to record-low levels in the United States, infectious disease "epidemics" on college campuses continue. A large student body with variable immunization status makes a college campus fertile ground for the spread of communicable diseases. The presence of international students and an increasingly large number of students traveling abroad make it essential that individuals charged with defining and instituting health-related policies for the university have knowledge about health issues occurring in foreign countries as well. Several safe and effective vaccines are available that offer protection to young adults from a variety of infectious diseases in the United States. Because vaccine-preventable diseases can cause both human and economic problems for colleges and universities, administrators should take steps to assure that the students on college campuses benefit from these vaccines.

[Acute painful crisis in a female Nigerian patient with sickle cell disease].

PubMed

Nin, Sayaka; Seki, Masanori; Maie, Koichiro; Kuroda, Akihiro; Miyamoto, Kana; Ogawa, Shinichi; Ito, Yufu; Kurita, Naoki; Yokoyama, Yasuhisa; Sakata Yanagimoto, Mamiko; Obara, Naoshi; Hasegawa, Yuichi; Ogino, Yasuko; Ito, Takayoshi; Chiba, Shigeru

2015-01-01

We report a 38-year-old Nigerian woman with sickle cell disease. Sickle cell disease had been diagnosed when she experienced her first sickle cell crisis episode at age 8 years. Thereafter, she had infrequent minor episodes. She visited a hospital presenting with fever, anemia, jaundice, and systemic pain, and was then transferred to our hospital. Together with rehydration and red blood cell transfusion, analgesics and antibiotics were prescribed, and produced gradual improvement of all symptoms and signs. The patient was discharged on day 9 of hospitalization. Sickle cell crisis is an acute painful episode caused by occlusion of arterioles. The degree of pain and accompanying symptoms, as well as the frequencies of crises, are variable. Moreover, one third of individuals with sickle cell disease never experience a crisis. As our society becomes increasingly globalized, the probabilities of encountering sickle cell disease patients will be higher.

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

The Hyperspectral Infrared Imager (HyspIRI) Public Health and Air Quality Applications

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey C.; Hook, Simon J.

2014-01-01

The neglected tropical diseases (NTDs), a group of chronic, debilitating, and poverty-promoting parasitic, bacterial, and some viral and fungal infections, are among the most common causes of illness of the poorest people living in developing countries. Abiotic environmental factors are important in determining the distribution of disease-causing vectors and their life-cycles. HyspIRI observations can be merged through a Land Data Assimilation System (LDAS) be used to drive spatially-explicit ecological models of NTD vectors distribution and life cycles. Assimilations will be driven by observational data LDAS and satellite-derived meteorological forcing data, parameter datasets, and assimilation observations. HyspIRI hyperspectral measurements would provide global measurements of surface mineralogy and biotic crusts important in accessing the impact of dust in human health. HyspIRI surface thermal measurements would also help identify the variability of dust sources due to surface moisture conditions and map mineralogy.

[Genetic variability of the bacterium Ralstonia solanacearum (Burkholderiales: Burholderiaceae) in the banana-growing region of Uraba (Colombia)].

PubMed

Cardozo, Carolina; Rodríguez, Paola; Cotes, José Miguel; Marín, Mauricio

2010-03-01

The banana moko disease, caused by the bacterium Ralstonia solanacearum, is one of the most important phytopathological problems of the banana agribusiness in tropical countries. In Uraba and Magdalena (Colombia), the main exporting regions of banana in Colombia, this disease causes a destruction estimated in 16.5 ha/year. The bacterium presents an extremely high level of genetic variation that affects control measures. This is the first study of its variation in Colombia and was done with AFLP molecular markers on a population of 100 isolates from banana plants, soils and "weeds". The high level of genetic diversity, with Nei and Shannon indexes of h=0.32 and I=0.48, respectively, and the AMOVA, showed that this population is subestructured (Fst=0.66): the host is the main factor of differentiation. Even so, previous tests show that all varieties have pathogenicity on Musa.

The Hyperspectral Infrared Imager (HyspIRI) Public Health and Air Quality Applications

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey C.; Hook, Simon J.

2013-01-01

The neglected tropical diseases (NTDs), a group of chronic, debilitating, and poverty-promoting parasitic, bacterial, and some viral and fungal infections, are among the most common causes of illness of the poorest people living in developing countries. Abiotic environmental factors are important in determining the distribution of disease-causing vectors and their life-cycles. HyspIRI observations can be merged through a Land Data Assimilation System (LDAS) be used to drive spatially-explicit ecological models of NTD vectors distribution & life cycles. Assimilations will be driven by observational data LDAS and satellite-derived meteorological forcing data, parameter datasets, and assimilation observations. HyspIRI hyperspectral measurements would provide global measurements of surface mineralogy and biotic crusts important in accessing the impact of dust in human health. HyspIRI surface thermal measurements would also help identify the variability of dust sources due to surface moisture conditions and map mineralogy.

The Hyperspectral Infrared Imager (HyspIRI) Public Health & Air Quality Applications

NASA Technical Reports Server (NTRS)

Luvall, Jeffrey C.; Hook, Simon J.

2013-01-01

The neglected tropical diseases (NTDs), a group of chronic, debilitating, and poverty-promoting parasitic, bacterial, and some viral and fungal infections, are among the most common causes of illness of the poorest people living in developing countries. Abiotic environmental factors are important in determining the distribution of disease-causing vectors and their life-cycles. HyspIRI observations can be merged through a Land Data Assimilation System (LDAS) be used to drive spatially-explicit ecological models of NTD vectors distribution & life cycles. Assimilations will be driven by observational data LDAS and satellite-derived meteorological forcing data, parameter datasets, and assimilation observations. HyspIRI hyperspectral measurements would provide global measurements of surface mineralogy and biotic crusts important in accessing the impact of dust in human health. HyspIRI surface thermal measurements would also help identify the variability of dust sources due to surface moisture conditions and map mineralogy.

Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1.

PubMed

Tiedt, Hannes O; Benjamin, Beate; Niedeggen, Michael; Lueschow, Andreas

2018-02-22

In rare cases, patients with Alzheimer disease (AD) present at an early age and with a family history suggestive of an autosomal dominant mode of inheritance. Mutations of the presenilin-1 (PSEN1) gene are the most common causes of dementia in these patients. Early-onset and particularly familial AD patients frequently present with variable non-amnestic cognitive symptoms such as visual, language or behavioural changes as well as non-cognitive, e.g. motor, symptoms. To investigate the phenotypic variability in carriers of the PSEN1 S170F mutation. We report a family with 4 patients carrying the S170F mutation of whom 2 underwent detailed clinical examinations. We discuss our current findings in the context of previously reported S170F cases. The clinical phenotype was consistent regarding initial memory impairment and early onset in the late twenties found in all S170F patients. There were frequent non-amnestic cognitive changes and, at early stages of the disease, indications of a more pronounced disturbance of visuospatial abilities as compared to face and object recognition. Non-cognitive symptoms most often included myoclonus and cerebellar ataxia. A review of the available case reports indicates some phenotypic variability associated with the S170F mutation including different constellations of symptoms such as parkinsonism and delusions. The variable clinical findings associated with the S170F mutation highlight the relevance of atypical phenotypes in the context of research and under a clinical perspective. CSF sampling and detection of Aβ species may be essential to indicate AD pathology in unclear cases presenting with cognitive and motor symptoms at a younger age. © 2018 S. Karger AG, Basel.

Spatially heterogeneous land cover/land use and climatic risk factors of tick-borne feline cytauxzoonosis.

PubMed

Raghavan, Ram K; Almes, Kelli; Goodin, Doug G; Harrington, John A; Stackhouse, Paul W

2014-07-01

Feline cytauxzoonosis is a highly fatal tick-borne disease caused by a hemoparasitic protozoan, Cytauxzoon felis. This disease is a leading cause of mortality for cats in the Midwestern United States, and no vaccine or effective treatment options exist. Prevention based on knowledge of risk factors is therefore vital. Associations of different environmental factors, including recent climate were evaluated as potential risk factors for cytauxzoonosis using Geographic Information Systems (GIS). There were 69 cases determined to be positive for cytauxzoonosis based upon positive identification of C. felis within blood film examinations, tissue impression smears, or histopathologic examination of tissues. Negative controls totaling 123 were selected from feline cases that had a history of fever, malaise, icterus, and anorexia but lack of C. felis within blood films, impression smears, or histopathologic examination of tissues. Additional criteria to rule out C. felis among controls were the presence of regenerative anemia, cytologic examination of blood marrow or lymph node aspirate, other causative agent diagnosed, or survival of 25 days or greater after testing. Potential environmental determinants were derived from publicly available sources, viz., US Department of Agriculture (soil attributes), US Geological Survey (land-cover/landscape, landscape metrics), and NASA (climate). Candidate variables were screened using univariate logistic models with a liberal p value (0.2), and associations with cytauxzoonosis were modeled using a global multivariate logistic model (p<0.05). Spatial heterogeneity among significant variables in the study region was modeled using a geographically weighted regression (GWR) approach. Total Edge Contrast Index (TECI), grassland-coverage, humidity conditions recorded during the 9(th) week prior to case arrival, and an interaction variable, "diurnal temperature range × percent mixed forest area" were significant risk factors for cytauxzoonosis in the study region. TECI and grassland areas exhibited significant regional differences in their effects on cytauxzoonosis outcome, whereas others were uniform. Land-cover areas favorable for tick habitats and climatic conditions that favor the tick life cycle are strong risk factors for feline cytauxzoonosis. Spatial heterogeneity and interaction effects between land-cover and climatic variables may reveal new information when evaluating risk factors for vector-borne diseases.

Proteomic and transcriptomic analysis of lung tissue in OVA-challenged mice.

PubMed

Lee, Yongjin; Hwang, Yun-Ho; Kim, Kwang-Jin; Park, Ae-Kyung; Paik, Man-Jeong; Kim, Seong Hwan; Lee, Su Ui; Yee, Sung-Tae; Son, Young-Jin

2018-01-01

Asthma is a long term inflammatory disease of the airway of lungs characterized by variable airflow obstruction and bronchospasm. Asthma is caused by a complex combination of environmental and genetic interactions. In this study, we conducted proteomic analysis of samples derived from control and OVA challenged mice for environmental respiratory disease by using 2-D gel electrophoresis. In addition, we explored the genes associated with the environmental substances that cause respiratory disease and conducted RNA-seq by next-generation sequencing. Proteomic analysis revealed 7 up-regulated (keratin KB40, CRP, HSP27, chaperonin containing TCP-1, TCP-10, keratin, and albumin) and 3 down-regulated proteins (PLC-α, PLA2, and precursor ApoA-1). The expression diversity of many genes was found in the lung tissue of OVA challenged moue by RNA-seq. 146 genes were identified as significantly differentially expressed by OVA treatment, and 118 genes of the 146 differentially expressed genes were up-regulated and 28 genes were downregulated. These genes were related to inflammation, mucin production, and airway remodeling. The results presented herein enable diagnosis and the identification of quantitative markers to monitor the progression of environmental respiratory disease using proteomics and genomic approaches.

Genetic testing in steroid-resistant nephrotic syndrome: why, who, when and how?

PubMed

Preston, Rebecca; Stuart, Helen M; Lennon, Rachel

2017-11-27

Steroid-resistant nephrotic syndrome (SRNS) is a common cause of chronic kidney disease in childhood and has a significant risk of rapid progression to end-stage renal disease. The identification of over 50 monogenic causes of SRNS has revealed dysfunction in podocyte-associated proteins in the pathogenesis of proteinuria, highlighting their essential role in glomerular function. Recent technological advances in high-throughput sequencing have enabled indication-driven genetic panel testing for patients with SRNS. The availability of genetic testing, combined with the significant phenotypic variability of monogenic SRNS, poses unique challenges for clinicians when directing genetic testing. This highlights the need for clear clinical guidelines that provide a systematic approach for mutational screening in SRNS. The likelihood of identifying a causative mutation is inversely related to age at disease onset and is increased with a positive family history or the presence of extra-renal manifestations. An unequivocal molecular diagnosis could allow for a personalised treatment approach with weaning of immunosuppressive therapy, avoidance of renal biopsy and provision of accurate, well-informed genetic counselling. Identification of novel causative mutations will continue to unravel the pathogenic mechanisms of glomerular disease and provide new insights into podocyte biology and glomerular function.

A Permutation-Randomization Approach to Test the Spatial Distribution of Plant Diseases.

PubMed

Lione, G; Gonthier, P

2016-01-01

The analysis of the spatial distribution of plant diseases requires the availability of trustworthy geostatistical methods. The mean distance tests (MDT) are here proposed as a series of permutation and randomization tests to assess the spatial distribution of plant diseases when the variable of phytopathological interest is categorical. A user-friendly software to perform the tests is provided. Estimates of power and type I error, obtained with Monte Carlo simulations, showed the reliability of the MDT (power > 0.80; type I error < 0.05). A biological validation on the spatial distribution of spores of two fungal pathogens causing root rot on conifers was successfully performed by verifying the consistency between the MDT responses and previously published data. An application of the MDT was carried out to analyze the relation between the plantation density and the distribution of the infection of Gnomoniopsis castanea, an emerging fungal pathogen causing nut rot on sweet chestnut. Trees carrying nuts infected by the pathogen were randomly distributed in areas with different plantation densities, suggesting that the distribution of G. castanea was not related to the plantation density. The MDT could be used to analyze the spatial distribution of plant diseases both in agricultural and natural ecosystems.

[The gastrointestinal tract microbiom in connective tissue diseases].

PubMed

Krajewska-Włodarczyk, Magdalena

Factors such as genetics, the environment, infections, and the human body microbiota, mainly gastrointestinal tract microbiota may play a role in the pathogenesis of autoimmune disorders. There is an increasing evidence that suggest an association between gastrointestinal tract dysbiosis, and in particular gut dysbiosis, and connective tissue diseases but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the normal or the favorable microbiome. Further studies are needed to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of connective tissue diseases and their clinical manifestations. The identification of dysbiosis specific for certain connective tissue diseases may help in the development of an individualized management for each patient. This review aims to summarize current data on the role of the gastrointestinal tract microbiome in connective tissue diseases.

Reaction Time and Mortality from the Major Causes of Death: The NHANES-III Study

PubMed Central

Hagger-Johnson, Gareth; Deary, Ian J.; Davies, Carolyn A.; Weiss, Alexander; Batty, G. David

2014-01-01

Objective Studies examining the relation of information processing speed, as measured by reaction time, with mortality are scarce. We explored these associations in a representative sample of the US population. Methods Participants were 5,134 adults (2,342 men) aged 20–59 years from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–94). Results Adjusted for age, sex, and ethnic minority status, a 1 SD slower reaction time was associated with a raised risk of mortality from all-causes (HR = 1.25, 95% CI 1.12, 1.39) and cardiovascular disease (CVD) (HR = 1.36, 95% CI 1.17, 1.58). Having 1 SD more variable reaction time was also associated with greater risk of all-cause (HR = 1.36, 95% CI 1.19, 1.55) and CVD (HR = 1.50, 95% CI 1.33, 1.70) mortality. No associations were observed for cancer mortality. The magnitude of the relationships was comparable in size to established risk factors in this dataset, such as smoking. Interpretation Alongside better-established risk factors, reaction time is associated with increased risk of premature death and cardiovascular disease. It is a candidate risk factor for all-cause and cause-specific mortality. PMID:24489645

Clinical characteristics and public health management of invasive meningococcal group W disease in the East Midlands region of England, United Kingdom, 2011 to 2013.

PubMed

Bethea, Jane; Makki, Sophia; Gray, Steve; MacGregor, Vanessa; Ladhani, Shamez

2016-06-16

In England and Wales, meningococcal disease caused by group W has historically been associated with outbreaks of disease among travellers to high-risk countries. Following a large outbreak associated with travel to the Hajj in 2000, the number of cases declined and, in 2008, only 19 laboratory-confirmed cases were identified nationally. In 2013, in the East Midlands region of England, eight cases of meningococcal disease caused by this serogroup were recorded, compared with six from 2011 to 2012. To explore this further, data for all cases with a date of onset between 1 January 2011 and 31 December 2013 were collected. Data collected included geographical location, clinical presentation and outcome. Fourteen cases were identified; two died as a result of their illness and two developed long-term health problems. No commonality in terms of geographical location, shared space or activities was identified, suggesting that group W is circulating endemically with local transmission. Clinical presentation was variable. Half presented with symptoms not typical of a classical meningococcal disease, including two cases of cellulitis, which may have implications for clinicians, in terms of timely identification and treatment, and public health specialists, for offering timely antibiotic chemoprophylaxis to close contacts. This article is copyright of The Authors, 2016.

A novel CLCN5 mutation in a boy with Bartter-like syndrome and partial growth hormone deficiency.

PubMed

Bogdanović, Radovan; Draaken, Markus; Toromanović, Alma; Dordević, Maja; Stajić, Natasa; Ludwig, Michael

2010-11-01

Dent disease is an X-linked recessive disorder affecting the proximal tubule and is characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis/nephrolithiasis with a variable number of features of Fanconi syndrome. It is most often associated with mutations in CLCN5, which encodes the endosomal electrogenic chloride/proton exchanger ClC-5. Renal acidification abnormalities are only rarely seen in Dent disease, whereas the hypokalemic metabolic alkalosis associated with hyperreninemic hyperaldosteronism (Bartter-like syndrome) has been reported in only one patient so far. We report on a 5-year-old boy with Dent disease caused by mutation in CLCN5 gene, c.1073G>A, who presented with hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism persisting over the entire follow-up. No mutations were found in NKCC2, ROMK, NCCT, or ClC-Kb genes. In addition, the patient exhibited growth failure associated with partial growth hormone (GH) deficiency. Coexistence of Bartter-like syndrome features with LMWP should prompt a clinician to search for Dent disease. The Bartter syndrome phenotype seen in Dent disease patients may represent a distinct form of Bartter syndrome, the exact mechanism of which has yet to be fully elucidated. Growth delay that persists in spite of appropriate therapy should raise suspicion of other causes, such as GH deficiency.

Molecular Mechanisms of Bacterial Pathogenicity

NASA Astrophysics Data System (ADS)

Fuchs, Thilo Martin

Cautious optimism has arisen over recent decades with respect to the long struggle against bacteria, viruses, and parasites. This has been offset, however, by a fatal complacency stemming from previous successes such as the development of antimicrobial drugs, the eradication of smallpox, and global immunization programs. Infectious diseases nevertheless remain the world's leading cause of death, killing at least 17 million persons annually [61]. Diarrheal diseases caused by Vibrio cholerae or Shigella dysenteriae kill about 3 million persons every year, most of them young children: Another 4 million die of tuberculosis or tetanus. Outbreaks of diphtheria in Eastern Europe threatens the population with a disease that had previously seemed to be overcome. Efforts to control infectious diseases more comprehensively are undermined not only by socioeconomic conditions but also by the nature of the pathogenic organisms itself; some isolates of Staphylococcus aureus and Enterobacter have become so resistant to drugs by horizontal gene transfer that they are almost untreatable. In addition, the mechanism of genetic variability helps pathogens to evade the human immune system, thus compromising the development of powerful vaccines. Therefore detailed knowledge of the molecular mechanisms of microbial pathogenicity is absolutely necessary to develop new strategies against infectious diseases and thus to lower their impact on human health and social development.

[The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literature review].

PubMed

Krajewska-Włodarczyk, Magdalena

Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.

Malaria's indirect contribution to all-cause mortality in the Andaman Islands during the colonial era.

PubMed

Shanks, G Dennis; Hay, Simon I; Bradley, David J

2008-09-01

Malaria has a substantial secondary effect on other causes of mortality. From the 19th century, malaria epidemics in the Andaman Islands' penal colony were initiated by the brackish swamp-breeding malaria vector Anopheles sundaicus and fuelled by the importation of new prisoners. Malaria was a major determinant of the highly variable all-cause mortality rate (correlation coefficient r(2)=0.60, n=68, p<0.0001) from 1872 to 1939. Directly attributed malaria mortality based on post-mortem examinations rarely exceeded one-fifth of total mortality. Infectious diseases such as pneumonia, tuberculosis, dysentery, and diarrhoea, which combined with malaria made up the majority of all-cause mortality, were positively correlated with malaria incidence over several decades. Deaths secondary to malaria (indirect malaria mortality) were at least as great as mortality directly attributed to malaria infections.

The effect of preexisting respiratory co-morbidities on burn outcomes☆

PubMed Central

Knowlin, Laquanda T.; Stanford, Lindsay B.; Cairns, Bruce A.; Charles, Anthony G.

2018-01-01

Introduction Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. Methods A retrospective analysis of patients admitted to a regional burn center from 2002–2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. Results There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01–1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10–2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Conclusion Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. PMID:28341260

The effect of preexisting respiratory co-morbidities on burn outcomes.

PubMed

Knowlin, Laquanda T; Stanford, Lindsay B; Cairns, Bruce A; Charles, Anthony G

2017-03-01

Burns cause physiologic changes in multiple organ systems in the body. Burn mortality is usually attributable to pulmonary complications, which can occur in up to 41% of patients admitted to the hospital after burn. Patients with preexisting comorbidities such as chronic lung diseases may be more susceptible. We therefore sought to examine the impact of preexisting respiratory disease on burn outcomes. A retrospective analysis of patients admitted to a regional burn center from 2002-2012. Independent variables analyzed included basic demographics, burn mechanism, presence of inhalation injury, TBSA, pre-existing comorbidities, smoker status, length of hospital stay, and days of mechanical ventilation. Bivariate analysis was performed and Cox regression modeling using significant variables was utilized to estimate hazard of progression to mechanical ventilation and mortality. There were a total of 7640 patients over the study period. Overall survival rate was 96%. 8% (n=672) had a preexisting respiratory disease. Chronic lung disease patients had a higher mortality rate (7%) compared to those without lung disease (4%, p<0.01). The adjusted Cox regression model to estimate the hazard of progression to mechanical ventilation in patients with respiratory disease was 21% higher compared to those without respiratory disease (HR=1.21, 95% CI=1.01-1.44). The hazard of progression to mortality is 56% higher (HR=1.56, 95% CI=1.10-2.19) for patients with pre-existing respiratory disease compared to those without respiratory disease after controlling for patient demographics and injury characteristics. Preexisting chronic respiratory disease significantly increases the hazard of progression to mechanical ventilation and mortality in patients following burn. Given the increasing number of Americans with chronic respiratory diseases, there will likely be a greater number of individuals at risk for worse outcomes following burn. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Development of single chain variable fragment (scFv) antibodies against Xylella fastidiosa subsp. pauca by phage display.

PubMed

Yuan, Qing; Jordan, Ramon; Brlansky, Ronald H; Istomina, Olga; Hartung, John

2015-10-01

Xylella fastidiosa is a member of the gamma proteobacteria. It is fastidious, insect-vectored and xylem-limited and causes a variety of diseases, some severe, on a wide range of economically important perennial crops, including grape and citrus. Antibody based detection assays are commercially available for X. fastidiosa, and are effective at the species, but not at the subspecies level. We have made a library of scFv antibody fragments directed against X. fastidiosa subsp. pauca strain 9a5c (citrus) by using phage display technology. Antibody gene repertoires were PCR-amplified using 23 primers for the heavy chain variable region (V(H)) and 21 primers for the light chain variable region (V(L)). The V(H) and V(L) were joined by overlap extension PCR, and then the genes of the scFv library were ligated into the phage vector pKM19. The library contained 1.2×10(7) independent clones with full-length scFv inserts. In each of 3cycles of affinity-selection with 9a5c, about 1.0×10(12) phage were used for panning with 4.1×10(6), 7.1×10(6), 2.1×10(7) phage recovered after the first, second and third cycles, respectively. Sixty-six percent of clones from the final library bound X. fastidiosa 9a5c in an ELISA. Some of these scFv antibodies recognized strain 9a5c and did not recognize X. fastidiosa strains that cause Pierce's disease of grapevine. Published by Elsevier B.V.

Climate change and vector-borne diseases: what are the implications for public health research and policy?

PubMed Central

Campbell-Lendrum, Diarmid; Manga, Lucien; Bagayoko, Magaran; Sommerfeld, Johannes

2015-01-01

Vector-borne diseases continue to contribute significantly to the global burden of disease, and cause epidemics that disrupt health security and cause wider socioeconomic impacts around the world. All are sensitive in different ways to weather and climate conditions, so that the ongoing trends of increasing temperature and more variable weather threaten to undermine recent global progress against these diseases. Here, we review the current state of the global public health effort to address this challenge, and outline related initiatives by the World Health Organization (WHO) and its partners. Much of the debate to date has centred on attribution of past changes in disease rates to climate change, and the use of scenario-based models to project future changes in risk for specific diseases. While these can give useful indications, the unavoidable uncertainty in such analyses, and contingency on other socioeconomic and public health determinants in the past or future, limit their utility as decision-support tools. For operational health agencies, the most pressing need is the strengthening of current disease control efforts to bring down current disease rates and manage short-term climate risks, which will, in turn, increase resilience to long-term climate change. The WHO and partner agencies are working through a range of programmes to (i) ensure political support and financial investment in preventive and curative interventions to bring down current disease burdens; (ii) promote a comprehensive approach to climate risk management; (iii) support applied research, through definition of global and regional research agendas, and targeted research initiatives on priority diseases and population groups. PMID:25688013

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

Identification of a novel missense mutation of MAF in a Japanese family with congenital cataract by whole exome sequencing: a clinical report and review of literature.

PubMed

Narumi, Yoko; Nishina, Sachiko; Tokimitsu, Motoharu; Aoki, Yoko; Kosaki, Rika; Wakui, Keiko; Azuma, Noriyuki; Murata, Toshinori; Takada, Fumio; Fukushima, Yoshimitsu; Kosho, Tomoki

2014-05-01

Congenital cataracts are the most important cause of severe visual impairment in infants. Genetic factors contribute to the disease development and 29 genes are known to cause congenital cataracts. Identifying the genetic cause of congenital cataracts can be difficult because of genetic heterogeneity. V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (MAF) encodes a basic region/leucine zipper transcription factor that plays a key role as a regulator of embryonic lens fiber cell development. MAF mutations have been reported to cause juvenile-onset pulverulent cataract, microcornea, iris coloboma, and other anterior segment dysgenesis. We report on six patients in a family who have congenital cataracts were identified MAF mutation by whole exome sequencing (WES). The heterozygous MAF mutation Q303L detected in the present family occurs in a well conserved glutamine residue at the basic region of the DNA-binding domain. All affected members showed congenital cataracts. Three of the six members showed microcornea and one showed iris coloboma. Congenital cataracts with MAF mutation exhibited phenotypically variable cataracts within the family. Review of the patients with MAF mutations supports the notion that congenital cataracts caused by MAF mutations could be accompanied by microcornea and/or iris coloboma. WES is a useful tool for detecting disease-causing mutations in patients with genetically heterogeneous conditions. © 2014 Wiley Periodicals, Inc.

Management of failure after surgery for gastro-esophageal reflux disease.

PubMed

Gronnier, C; Degrandi, O; Collet, D

2018-04-01

Surgical treatment of gastro-esophageal reflux disease (ST-GERD) is well-codified and offers an alternative to long-term medical treatment with a better efficacy for short and long-term outcomes. However, failure of ST-GERD is observed in 2-20% of patients; management is challenging and not standardized. The aim of this study is to analyze the causes of failure and to provide a treatment algorithm. The clinical aspects of ST-GERD failure are variable including persistent reflux, dysphagia or permanent discomfort leading to an important degradation of the quality of life. A morphological and functional pre-therapeutic evaluation is necessary to: (i) determine whether the symptoms are due to recurrence of reflux or to an error in initial indication and (ii) to understand the cause of the failure. The most frequent causes of failure of ST-GERD include errors in the initial indication, which often only need medical treatment, and surgical technical errors, for which surgical redo surgery can be difficult. Multidisciplinary management is necessary in order to offer the best-adapted treatment. Copyright © 2018. Published by Elsevier Masson SAS.

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

PubMed

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

2012-12-01

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

[Myofibrillar myopaathy].

PubMed

Hayashi, Yukiko

2013-01-01

Myofibrillar myopathy (MFM) is a group of hereditary disorders pathologically characterized by focal disorganizations of myofibril structures with cytoplasmic inclusions. Most of the diseases so-called desmin-related or storage myopathy, cytoplasmic body myopathy, spheroid body myopathy, reducing body myopathy, and hyaline body myopathy are included in MFM. Several causative genes have been identified such as DES, CRYAB, MYOT, ZASP, BAG3, FLNC, DNAJB6, FHL1, TTN, and VCP. Most of these genes encode Z-line related proteins or proteins associated with protein quality control. Since MFM is the name from pathological characteristics, clinical features of the patients including the age at disease onset, affected muscles, disease course, and complications are quite variable. In this paper, characteristic clinical and pathological features of each causative gene are summarized. Unexpectedly, hereditary myopathy with early respiratory failure (HMERF) caused by mutation in the A-band region of TTN is the most common cause of MFM in our cohort. Despite of intensive mutation screening, the causative gene of more than 60% of MFM patients is still unknown. Further identification of novel causative genes and elucidate pathomechanisms of protein aggregation in necessary.

Increased Grik4 Gene Dosage Causes Imbalanced Circuit Output and Human Disease-Related Behaviors.

PubMed

Arora, Vineet; Pecoraro, Valeria; Aller, M Isabel; Román, Celia; Paternain, Ana V; Lerma, Juan

2018-06-26

Altered glutamatergic neurotransmission is thought to contribute to mental disorders and neurodegenerative diseases. Copy-number variation in genes associated with glutamatergic synapses represents a source of genetic variability, possibly underlying neurological and mental disease susceptibility. The GRIK4 gene encodes a high-affinity kainate receptor subunit of essentially unknown function, although de novo duplication of the 11q23.3-q24.1 locus to which it maps has been detected in autism and other disorders. To determine how changes in the dose of Grik4 affect synaptic activity, we studied mice overexpressing this gene in the forebrain. A mild gain in Grik4 enhances synaptic transmission, causing a persistent imbalance in inhibitory and excitatory activity and disturbing the circuits responsible for the main amygdala outputs. These changes in glutamatergic activity reverse when Grik4 levels are normalized; thus, they may account for the behavioral abnormalities in disorders like autism or schizophrenia. Copyright © 2018 Agencia Estatal Consejo Superior de Investigaciones Científicas. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2008-04-01

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

Possibility of biological control of primocane fruiting raspberry disease caused by Fusarium sambucinum.

PubMed

Shternshis, Margarita V; Belyaev, Anatoly A; Matchenko, Nina S; Shpatova, Tatyana V; Lelyak, Anastasya A

2015-10-01

Biological control agents are a promising alternative to chemical pesticides for plant disease suppression. The main advantage of the natural biocontrol agents, such as antagonistic bacteria compared with chemicals, includes environmental pollution prevention and a decrease of chemical residues in fruits. This study is aimed to evaluate the impact of three Bacillus strains on disease of primocane fruiting raspberry canes caused by Fusarium sambucinum under controlled infection load and uncontrolled environmental factors. Bacillus subtilis, Bacillus licheniformis, and Bacillus amyloliquefaciens were used for biocontrol of plant disease in 2013 and 2014 which differed by environmental conditions. The test suspensions were 10(5) CFU/ml for each bacterial strain. To estimate the effect of biological agents on Fusarium disease, canes were cut at the end of vegetation, and the area of outer and internal lesions was measured. In addition to antagonistic effect, the strains revealed the ability to induce plant resistance comparable with chitosan-based formulation. Under variable ways of cane treatment by bacterial strains, the more effective were B. subtilis and B. licheniformis demonstrating dual biocontrol effect. However, environmental factors were shown to impact the strain biocontrol ability; changes in air temperature and humidity led to the enhanced activity of B. amyloliquefaciens. For the first time, the possibility of replacing chemicals with environmentally benign biological agents for ecologically safe control of the raspberry primocane fruiting disease was shown.

Close-wedge osteotomy for bony locking stiffness of the elbow in Gorham disease patients: a case report.

PubMed

Wang, Hsien-Chung; Lin, Gau-Tyan

2004-05-01

Gorham disease is a so-called massive idiopathic osteolysis or vanishing bone disorder. Massive osteolysis remains an enigmatic condition that involves various skeletal locations and is caused by endothelial proliferation. The diagnosis is difficult and is established via the association of clinical, radiologic and histologic pictures. Treatment modalities yield variable results. We report a case of vanishing bone in the elbow joint and carpal bones following trauma. This 13-year-old boy complained of severe restricted motion and deformity of the right elbow. We managed the problem using arthroplasty with close-wedge osteotomy on the lateral condyle of the humerus.

Gait variability in community dwelling adults with Alzheimer disease.

PubMed

Webster, Kate E; Merory, John R; Wittwer, Joanne E

2006-01-01

Studies have shown that measures of gait variability are associated with falling in older adults. However, few studies have measured gait variability in people with Alzheimer disease, despite the high incidence of falls in Alzheimer disease. The purpose of this study was to compare gait variability of community-dwelling older adults with Alzheimer disease and control subjects at various walking speeds. Ten subjects with mild-moderate Alzheimer disease and ten matched control subjects underwent gait analysis using an electronic walkway. Participants were required to walk at self-selected slow, preferred, and fast speeds. Stride length and step width variability were determined using the coefficient of variation. Results showed that stride length variability was significantly greater in the Alzheimer disease group compared with the control group at all speeds. In both groups, increases in walking speed were significantly correlated with decreases in stride length variability. Step width variability was significantly reduced in the Alzheimer disease group compared with the control group at slow speed only. In conclusion, there is an increase in stride length variability in Alzheimer disease at all walking speeds that may contribute to the increased incidence of falls in Alzheimer disease.

Emergency multiple sclerosis hospital admissions attributable to chemical and acoustic pollution: Madrid (Spain), 2001-2009.

PubMed

Carmona, Rocío; Linares, Cristina; Recio, Alberto; Ortiz, Cristina; Díaz, Julio

2018-01-15

Multiple sclerosis (MS) is the most prevalent neurological disease among young adults in Spain. A number of recent studies have linked traffic-related pollution, both chemical and acoustic, to the aetiology and exacerbation of neurodegenerative diseases. To analyse the existence of a significant short-term association between daily emergency MS hospital admissions and chemical and acoustic pollution caused by traffic in Madrid. We conducted a longitudinal ecological time series study, in which the dependent variable was the number of daily emergency MS hospital admissions (ICD-9: 340) registered in Madrid from 1 January 2001 to 31 December 2009. The independent variables were daily mean concentrations (μg/m 3 ) of PM 2.5 , PM 10 , O 3 and NO 2 . Equivalent diurnal (Leqd), nocturnal (Leqn) and daily equivalent noise levels (Leq24) were also considered. In addition, we controlled for linear trends, seasonality and the autoregressive nature of the series itself. Day of the week was also added as a covariate. Significant environmental variables were determined using Poisson GLM models. Relative risk (RR) and attributable risk (AR) values were calculated for increases of 10μg/m 3 in the case of chemical pollutants and 1dB(A) in noise levels. While there was no association between chemical pollutants caused by traffic and MS admissions, such an association was in evidence for Leqd at lag zero. This association is linear without a threshold, with there being a level above 67dB(A) from which this effect is more pronounced. The RRs were as follows: for all Leqd values, 1.21 (95% CI: 1.16, 1.26); and for Leqd >67dB(A), 1.62 (95% CI: 1.24, 2.13). The above results indicate that traffic noise can exacerbate MS symptoms, leading to hospital admissions due to this cause. Copyright © 2017 Elsevier B.V. All rights reserved.

Heart rate variability (HRV) in kidney failure: measurement and consequences of reduced HRV.

PubMed

Ranpuria, Reena; Hall, Martica; Chan, Chris T; Unruh, Mark

2008-02-01

A common cause of death in end-stage renal disease (ESRD) patients on dialysis is sudden cardiac death (SCD). Compared to the general population, the percentage of cardiovascular deaths that are attributed to SCD is higher in patients treated by dialysis. While coronary artery disease (CAD) is the predominant cause of SCD in dialysis patients, reduced heart rate variability (HRV) may play a role in the higher risk of SCD among other risk factors. HRV refers to beat-to-beat alterations in heart rate as measured by periodic variation in the R-R interval. HRV provides a non-invasive method for investigating autonomic input into the heart. It quantifies the amount by which the R-R interval or heart rate changes from one cardiac cycle to the next. The autonomic nervous system transmits impulses from the central nervous system to peripheral organs and is responsible for controlling the heart rate, blood pressure and respiratory activity. In normal individuals, without cardiac disease, the heart rate has a high degree of beat-to-beat variability. HRV fluctuates with respiration: it increases with inspiration and decreases with expiration and is primarily mediated by parasympathetic activity. HRV has been used to evaluate and quantify the cardiac risk associated with a variety of conditions including cardiac disorders, stroke, multiple sclerosis and diabetes. In this narrative review, we will examine the association between HRV and SCD. This report explains the measurement of HRV and the consequences of reduced HRV in the general population and dialysis patients. Lastly, this review will outline the possible use of HRV as a clinical predictor for SCD in the dialysis population. The current understanding of SCD based on HRV findings among the ESRD population support the use of more aggressive treatment of CAD; greater use of angiotensin converting enzyme inhibitor (ACE-i)/angiotensin receptor blockers (ARBs) and beta-blockers and more frequent and/or nocturnal haemodialysis to improve the survival of a patient with kidney failure.

Impact of Selected Socio-demographic Factors on the Development of Mortality due to Circulatory System Diseases in the Slovak Republic.

PubMed

Gavurová, Beáta; Kubák, Matúš

2017-12-01

We mapped the situation within a group of diseases of the circulatory system (I00-I99) in the Slovak Republic during 1996-2014. We focused mainly on spatiotemporal differences in mortality while controlling for age and sex. We performed binary logistic regression aiming to reveal socio-demographic factors that influence the odds of dying due to diseases of the circulatory system (I00-I99). In our analysis, the dependent variable was death diagnosis and the independent variables were age, region, gender, and marital status. Our findings suggest that odds of dying due to diseases of the circulatory system (I00-I99) increased for every year of age by 5.4%. Within the period from 1996 to 2014, the risk of dying from diseases of the circulatory system decreased by 2% every year. We also documented the fact that being female raised the odds of dying due to diseases of the circulatory system (I00-I99) by 12.9% compared to males. Furthermore, it could be argued that serious differences in terms of regional distribution of deaths caused by diseases of the circulatory system (I00-I99) exist in the Slovak Republic. We present the development of diseases of the circulatory system (I00-I99) in the Slovak Republic. Differences in spatial distribution of deaths are documented as well as related gender differences. Our study can serve as a tool for policy makers and benchmark for professionals. Copyright© by the National Institute of Public Health, Prague 2017.

New insights into the characterization of Colletotrichum species associated with apple diseases in southern Brazil and Uruguay.

PubMed

Velho, Aline Cristina; Alaniz, Sandra; Casanova, Leticia; Mondino, Pedro; Stadnik, Marciel J

2015-04-01

Colletotrichum species are associated with Apple bitter rot (ABR) and Glomerella leaf spot (GLS). Whereas both apple diseases occur frequently in Brazil, only the former has been reported in Uruguay. This work was aimed at identifying and comparing morpho-cultural characteristics and pathogenic variability of thirty-nine Colletotrichum isolates from both countries. Sequencing of the internal transcribed spacer (ITS) rDNA, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and β-tubulin (TUB2) allowed the identification of three species causing ABR and GLS in Brazil, i.e., Colletotrichum fructicola, Colletotrichum karstii, and Colletotrichum nymphaeae; and three species causing ABR in Uruguay, i.e., C. fructicola, Colletotrichum theobromicola, and Colletotrichum melonis. Six groups of colony colours were recorded with group 1 (mycelium white to pink and in reverse pinkish) and group 2 (mycelium white to grey and in reverse pinkish) the most frequent. Isolates of C. fructicola and C. theobromicola were sensitive to benomyl, while C. karstii, C. nymphaeae, and C. melonis were resistant. Conidia were predominantly cylindrical for C. fructicola and C. karstii, fusiform for C. nymphaeae and C. melonis, and obclavate for C. theobromicola. Brazilian isolates caused ABR in wounded fruits, but only five in non-wounded ones. Uruguayan isolates produced symptoms in fruits with or without previous wounding. All Brazilian isolates from GLS and twelve from ABR were able to cause GLS symptoms, while a sole Uruguayan ABR-isolate caused leaf spot symptoms. This study gives a better insight on the new species causing apple disease in both countries and discusses their pathogenic potential. Copyright © 2014 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Reserves as tools for alleviating impacts of marine disease

PubMed Central

Wenger, Amelia S.; Devlin, Michelle J.; Ceccarelli, Daniela M.; Williamson, David H.; Willis, Bette L.

2016-01-01

Marine protected areas can prevent over-exploitation, but their effect on marine diseases is less clear. We examined how marine reserves can reduce diseases affecting reef-building corals following acute and chronic disturbances. One year after a severe tropical cyclone, corals inside reserves had sevenfold lower levels of disease than those in non-reserves. Similarly, disease prevalence was threefold lower on reserve reefs following chronic exposure to terrestrial run-off from a degraded river catchment, when exposure duration was below the long-term site average. Examination of 35 predictor variables indicated that lower levels of derelict fishing line and injured corals inside reserves were correlated with lower levels of coral disease in both case studies, signifying that successful disease mitigation occurs when activities that damage reefs are restricted. Conversely, reserves were ineffective in moderating disease when sites were exposed to higher than average levels of run-off, demonstrating that reductions in water quality undermine resilience afforded by reserve protection. In addition to implementing protected areas, we highlight that disease management efforts should also target improving water quality and limiting anthropogenic activities that cause injury. PMID:26880842

Reserves as tools for alleviating impacts of marine disease.

PubMed

Lamb, Joleah B; Wenger, Amelia S; Devlin, Michelle J; Ceccarelli, Daniela M; Williamson, David H; Willis, Bette L

2016-03-05

Marine protected areas can prevent over-exploitation, but their effect on marine diseases is less clear. We examined how marine reserves can reduce diseases affecting reef-building corals following acute and chronic disturbances. One year after a severe tropical cyclone, corals inside reserves had sevenfold lower levels of disease than those in non-reserves. Similarly, disease prevalence was threefold lower on reserve reefs following chronic exposure to terrestrial run-off from a degraded river catchment, when exposure duration was below the long-term site average. Examination of 35 predictor variables indicated that lower levels of derelict fishing line and injured corals inside reserves were correlated with lower levels of coral disease in both case studies, signifying that successful disease mitigation occurs when activities that damage reefs are restricted. Conversely, reserves were ineffective in moderating disease when sites were exposed to higher than average levels of run-off, demonstrating that reductions in water quality undermine resilience afforded by reserve protection. In addition to implementing protected areas, we highlight that disease management efforts should also target improving water quality and limiting anthropogenic activities that cause injury. © 2016 The Author(s).

Demographic, social, and economic effects on Mexican causes of death in 1990.

PubMed

Pick, J B; Butler, E W

1998-01-01

This study examined spatial geographic patterns of cause of death and 28 demographic and socioeconomic influences on causes of death for 31 Mexican states plus the Federal District for 1990. Mortality data were obtained from the state death registration system and are age standardized. The 28 socioeconomic variables were obtained from Census records. Analysis included 2 submodels: one with all 28 socioeconomic variables in a stepwise regression, and one with each of the 4 groups of factors. The conceptual model is based on epidemiological transition theory and empirical findings. There are 4 stages in mortality decline. Effects are grouped as demographic, sociocultural, economic prosperity, and housing, health, and crime factors. Findings indicate that cancer and cardiovascular disease were strongly correlated and consistently high in border areas as well as the Federal District and Jalisco. Respiratory mortality had higher values in the Federal District, Puebla, and surrounding states, as well as Jalisco. The standardized total mortality rate was only in simple correlations associated inversely with underemployment. All cause specific mortality was associated with individual factors. Respiratory mortality was linked with manufacturing work force. Cardiovascular and cancer mortality were associated with socioeconomic factors. In submodel I, cause specific mortality was predicted by crowding, housing characteristics, marriage and divorce, and manufacturing work force. In submodel II, economic group factors had the strongest model fits explaining 33-60% of the "r" square. Hypothesized effects were only partially validated.

Diagnostic Challenges in Retinitis Pigmentosa: Genotypic Multiplicity and Phenotypic Variability

PubMed Central

Chang, Susie; Vaccarella, Leah; Olatunji, Sunday; Cebulla, Colleen; Christoforidis, John

2011-01-01

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders. Diagnosis can be challenging as more than 40 genes are known to cause non-syndromic RP and phenotypic expression can differ significantly resulting in variations in disease severity, age of onset, rate of progression, and clinical findings. We describe the clinical manifestations of RP, the more commonly known causative gene mutations, and the genotypic-phenotypic correlation of RP. PMID:22131872

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.

Climate change and habitat fragmentation drive the occurrence of Borrelia burgdorferi, the agent of Lyme disease, at the northeastern limit of its distribution

PubMed Central

Simon, Julie A; Marrotte, Robby R; Desrosiers, Nathalie; Fiset, Jessica; Gaitan, Jorge; Gonzalez, Andrew; Koffi, Jules K; Lapointe, Francois-Joseph; Leighton, Patrick A; Lindsay, Lindsay R; Logan, Travis; Milord, Francois; Ogden, Nicholas H; Rogic, Anita; Roy-Dufresne, Emilie; Suter, Daniel; Tessier, Nathalie; Millien, Virginie

2014-01-01

Lyme borreliosis is rapidly emerging in Canada, and climate change is likely a key driver of the northern spread of the disease in North America. We used field and modeling approaches to predict the risk of occurrence of Borrelia burgdorferi, the bacteria causing Lyme disease in North America. We combined climatic and landscape variables to model the current and future (2050) potential distribution of the black-legged tick and the white-footed mouse at the northeastern range limit of Lyme disease and estimated a risk index for B. burgdorferi from these distributions. The risk index was mostly constrained by the distribution of the white-footed mouse, driven by winter climatic conditions. The next factor contributing to the risk index was the distribution of the black-legged tick, estimated from the temperature. Landscape variables such as forest habitat and connectivity contributed little to the risk index. We predict a further northern expansion of B. burgdorferi of approximately 250–500 km by 2050 – a rate of 3.5–11 km per year – and identify areas of rapid rise in the risk of occurrence of B. burgdorferi. Our results will improve understanding of the spread of Lyme disease and inform management strategies at the most northern limit of its distribution. PMID:25469157

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

Distinct prion-like strains of amyloid beta implicated in phenotypic diversity of Alzheimer's disease.

PubMed

Cohen, Mark; Appleby, Brian; Safar, Jiri G

2016-01-01

Vast evidence on human prions demonstrates that variable disease phenotypes, rates of propagation, and targeting of distinct brain structures are determined by unique conformers (strains) of pathogenic prion protein (PrP(Sc)). Recent progress in the development of advanced biophysical tools that inventory structural characteristics of amyloid beta (Aβ) in the brain cortex of phenotypically diverse Alzheimer's disease (AD) patients, revealed unique spectrum of oligomeric particles in the cortex of rapidly progressive cases, implicating these structures in variable rates of propagation in the brain, and in distict disease manifestation. Since only ∼30% of phenotypic diversity of AD can be explained by polymorphisms in risk genes, these and transgenic bioassay data argue that structurally distinct Aβ particles play a major role in the diverse pathogenesis of AD, and may behave as distinct prion-like strains encoding diverse phenotypes. From these observations and our growing understanding of prions, there is a critical need for new strain-specific diagnostic strategies for misfolded proteins causing these elusive disorders. Since targeted drug therapy can induce mutation and evolution of prions into new strains, effective treatments of AD will require drugs that enhance clearance of pathogenic conformers, reduce the precursor protein, or inhibit the conversion of precursors into prion-like states.

Modeling of leishmaniasis infection dynamics: novel application to the design of effective therapies

PubMed Central

2012-01-01

Background The WHO considers leishmaniasis as one of the six most important tropical diseases worldwide. It is caused by parasites of the genus Leishmania that are passed on to humans and animals by the phlebotomine sandfly. Despite all of the research, there is still a lack of understanding on the metabolism of the parasite and the progression of the disease. In this study, a mathematical model of disease progression was developed based on experimental data of clinical symptoms, immunological responses, and parasite load for Leishmania amazonensis in BALB/c mice. Results Four biologically significant variables were chosen to develop a differential equation model based on the GMA power-law formalism. Parameters were determined to minimize error in the model dynamics and time series experimental data. Subsequently, the model robustness was tested and the model predictions were verified by comparing them with experimental observations made in different experimental conditions. The model obtained helps to quantify relationships between the selected variables, leads to a better understanding of disease progression, and aids in the identification of crucial points for introducing therapeutic methods. Conclusions Our model can be used to identify the biological factors that must be changed to minimize parasite load in the host body, and contributes to the design of effective therapies. PMID:22222070

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.

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.

Prevalence of anemia and malnutrition and their association in elderly nursing home residents.

PubMed

Sahin, Sevnaz; Tasar, Pinar Tosun; Simsek, Hatice; Çicek, Zeynep; Eskiizmirli, Hulya; Aykar, Fisun Senuzun; Sahin, Fahri; Akcicek, Fehmi

2016-10-01

Malnutrition is one of the most important geriatric syndromes in the elderly. The aim of this study was to investigate the association between anemia and malnutrition in elderly nursing home residents. Local nursing home residents over 60 years old in the Izmir were included in the study. Blood samples were taken from study participants for hemogram, iron, ferritin, total iron-binding capacity, vitamin B12 and folic acid analysis. WHO criteria were used to define anemia. Causes of anemia were classified as iron deficiency, vitamin B12 or folic acid deficiency, anemia of chronic disease or other hematologic causes. Anemia was defined as the dependent variable and malnutrition was defined as the independent variable. Correlation between MNA scores and Hb levels was determined using Pearson correlation analysis. The slope of causality between malnutrition and anemia was determined using the χ (2) test and logistic regression analysis. The study included 257 elderly nursing home residents with a mean age of 78.5 ± 7.8 years. The overall prevalence of anemia was 54.9 %; 35.8 % of the study participants were at risk of malnutrition and 8.2 % were malnourished. Anemia risk was 2.12-fold higher in participants at risk of malnutrition and 5.05-fold higher in those with malnutrition. In the participants with malnutrition or malnutrition risk, the most common cause of anemia was anemia of chronic disease (57.1 and 46.5 %, respectively). The prevalence of anemia among elderly nursing home residents is high in Turkey. Malnutrition and malnutrition risk increase the incidence of anemia.

A U.S. perspective on the adverse reactions from traditional Chinese medicines.

PubMed

Ko, Richard J

2004-03-01

Traditional Chinese medicines (TCM) are popular in the United States and Asian and non-Asian consumers are using the product for disease treatment and health prevention. As more people are using TCM products, there are increased reports on adverse reactions. This review will focus on adverse reactions due to TCM as reported in the literature. The review is based on MedLine search of literatures using keywords including: herbs, herbal, traditional Chinese medicines with toxicity, adverse effects, death, drug interaction and pharmacokinetic. In addition, specific searches were performed using the above keywords with the common name and the scientific name of the plant product. The causes of adverse reactions associated with TCM are diverse. They include variability in active/toxic ingredients due to growing conditions, use of inherent toxic herbs causing toxicity, overdose of herbs, drug-herb interactions especially with pharmaceuticals that have narrow therapeutic index, coexisting diseases, and idiosyncratic reactions like allergy, hepatitis and anaphylaxis. Other adverse reactions can be due to manufacturing and quality problems causing adulteration, misidentification, substitution of one herb with another, variability in the amount of active ingredients, use of pharmaceuticals without identifying on the labels, improper processing and preparation, and contamination. To minimize the adverse reactions from TCM and protect the public, there must be adequate laws and regulations to ensure that products are manufactured with the highest standards. Manufacturers should be licensed by regulatory agency and manufactured under good manufacturing practice. TCM products must be evaluated for their safety before marketing. Proper labeling and good surveillance systems shall ensure the protection of the consumers.

Effect of depression on mortality and cardiovascular morbidity in type 2 diabetes mellitus after 3 years follow up. The DIADEMA study protocol.

PubMed

de Burgos-Lunar, Carmen; Gómez-Campelo, Paloma; Cárdenas-Valladolid, Juan; Fuentes-Rodríguez, Carmen Y; Granados-Menéndez, María I; López-López, Francisco; Salinero-Fort, Miguel A

2012-07-30

Type 2 diabetes mellitus and depression are highly prevalent diseases that are associated with an increased risk of cardiovascular disease and mortality. There is evidence about a bidirectional association between depressive symptoms and type 2 diabetes mellitus. However, prognostic implications of the joint effects of these two diseases on cardiovascular morbidity and mortality are not well-known. A three-year, observational, prospective, cohort study, carried out in Primary Health Care Centres in Madrid (Spain). The project aims to analyze the effect of depression on cardiovascular events, all-cause and cardiovascular mortality in patients with type 2 diabetes mellitus, and to estimate a clinical predictive model of depression in these patients.The number of patients required is 3255, all them with type 2 diabetes mellitus, older than 18 years, who regularly visit their Primary Health Care Centres and agree to participate. They are chosen by simple random sampling from the list of patients with type 2 diabetes mellitus of each general practitioner.The main outcome measures are all-cause and cardiovascular mortality and cardiovascular morbidity; and exposure variable is the major depressive disorder.There will be a comparison between depressed and not depressed patients in all-cause mortality, cardiovascular mortality, coronary artery disease and stroke using the Chi-squared test. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors that might alter the effect recorded will be taken into account in this analysis. To assess the effect of depression on the mortality, a survival analysis will be used comparing the two groups using the log-rank test. The control of potential confounding variables will be performed by the construction of a Cox regression model. Our study's main contribution is to evaluate the increase in the risk of cardiovascular morbidity and mortality, in depressed Spanish adults with type 2 diabetes mellitus attended in Primary Health Care Setting. It would also be useful to identify subgroups of patients for which the interventions could be more beneficial.

Effect of depression on mortality and cardiovascular morbidity in type 2 diabetes mellitus after 3 years follow up. The DIADEMA study protocol

PubMed Central

2012-01-01

Background Type 2 diabetes mellitus and depression are highly prevalent diseases that are associated with an increased risk of cardiovascular disease and mortality. There is evidence about a bidirectional association between depressive symptoms and type 2 diabetes mellitus. However, prognostic implications of the joint effects of these two diseases on cardiovascular morbidity and mortality are not well-known. Method/design A three-year, observational, prospective, cohort study, carried out in Primary Health Care Centres in Madrid (Spain). The project aims to analyze the effect of depression on cardiovascular events, all-cause and cardiovascular mortality in patients with type 2 diabetes mellitus, and to estimate a clinical predictive model of depression in these patients. The number of patients required is 3255, all them with type 2 diabetes mellitus, older than 18 years, who regularly visit their Primary Health Care Centres and agree to participate. They are chosen by simple random sampling from the list of patients with type 2 diabetes mellitus of each general practitioner. The main outcome measures are all-cause and cardiovascular mortality and cardiovascular morbidity; and exposure variable is the major depressive disorder. There will be a comparison between depressed and not depressed patients in all-cause mortality, cardiovascular mortality, coronary artery disease and stroke using the Chi-squared test. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors that might alter the effect recorded will be taken into account in this analysis. To assess the effect of depression on the mortality, a survival analysis will be used comparing the two groups using the log-rank test. The control of potential confounding variables will be performed by the construction of a Cox regression model. Discussion Our study’s main contribution is to evaluate the increase in the risk of cardiovascular morbidity and mortality, in depressed Spanish adults with type 2 diabetes mellitus attended in Primary Health Care Setting. It would also be useful to identify subgroups of patients for which the interventions could be more beneficial. PMID:22846516

What variables are important in predicting bovine viral diarrhea virus? A random forest approach.

PubMed

Machado, Gustavo; Mendoza, Mariana Recamonde; Corbellini, Luis Gustavo

2015-07-24

Bovine viral diarrhea virus (BVDV) causes one of the most economically important diseases in cattle, and the virus is found worldwide. A better understanding of the disease associated factors is a crucial step towards the definition of strategies for control and eradication. In this study we trained a random forest (RF) prediction model and performed variable importance analysis to identify factors associated with BVDV occurrence. In addition, we assessed the influence of features selection on RF performance and evaluated its predictive power relative to other popular classifiers and to logistic regression. We found that RF classification model resulted in an average error rate of 32.03% for the negative class (negative for BVDV) and 36.78% for the positive class (positive for BVDV).The RF model presented area under the ROC curve equal to 0.702. Variable importance analysis revealed that important predictors of BVDV occurrence were: a) who inseminates the animals, b) number of neighboring farms that have cattle and c) rectal palpation performed routinely. Our results suggest that the use of machine learning algorithms, especially RF, is a promising methodology for the analysis of cross-sectional studies, presenting a satisfactory predictive power and the ability to identify predictors that represent potential risk factors for BVDV investigation. We examined classical predictors and found some new and hard to control practices that may lead to the spread of this disease within and among farms, mainly regarding poor or neglected reproduction management, which should be considered for disease control and eradication.

A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments

PubMed Central

Stirnemann, Jérôme; Belmatoug, Nadia; Camou, Fabrice; Serratrice, Christine; Froissart, Roseline; Caillaud, Catherine; Levade, Thierry; Astudillo, Leonardo; Serratrice, Jacques; Brassier, Anaïs; Rose, Christian; Billette de Villemeur, Thierry; Berger, Marc G.

2017-01-01

Gaucher disease (GD, ORPHA355) is a rare, autosomal recessive genetic disorder. It is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase, which leads to an accumulation of its substrate, glucosylceramide, in macrophages. In the general population, its incidence is approximately 1/40,000 to 1/60,000 births, rising to 1/800 in Ashkenazi Jews. The main cause of the cytopenia, splenomegaly, hepatomegaly, and bone lesions associated with the disease is considered to be the infiltration of the bone marrow, spleen, and liver by Gaucher cells. Type-1 Gaucher disease, which affects the majority of patients (90% in Europe and USA, but less in other regions), is characterized by effects on the viscera, whereas types 2 and 3 are also associated with neurological impairment, either severe in type 2 or variable in type 3. A diagnosis of GD can be confirmed by demonstrating the deficiency of acid glucocerebrosidase activity in leukocytes. Mutations in the GBA1 gene should be identified as they may be of prognostic value in some cases. Patients with type-1 GD—but also carriers of GBA1 mutation—have been found to be predisposed to developing Parkinson’s disease, and the risk of neoplasia associated with the disease is still subject to discussion. Disease-specific treatment consists of intravenous enzyme replacement therapy (ERT) using one of the currently available molecules (imiglucerase, velaglucerase, or taliglucerase). Orally administered inhibitors of glucosylceramide biosynthesis can also be used (miglustat or eliglustat). PMID:28218669

Linkages of Weather and Climate With Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae), Enzootic Transmission of Borrelia burgdorferi, and Lyme Disease in North America.

PubMed

Eisen, Rebecca J; Eisen, Lars; Ogden, Nicholas H; Beard, Charles B

2016-03-01

Lyme disease has increased both in incidence and geographic extent in the United States and Canada over the past two decades. One of the underlying causes is changes during the same time period in the distribution and abundance of the primary vectors: Ixodes scapularis Say and Ixodes pacificus Cooley and Kohls in eastern and western North America, respectively. Aside from short periods of time when they are feeding on hosts, these ticks exist in the environment where temperature and relative humidity directly affect their development, survival, and host-seeking behavior. Other important factors that strongly influence tick abundance as well as the proportion of ticks infected with the Lyme disease spirochete, Borrelia burgdorferi, include the abundance of hosts for the ticks and the capacity of tick hosts to serve as B. burgdorferi reservoirs. Here, we explore the linkages between climate variation and: 1) duration of the seasonal period and the timing of peak activity; 2) geographic tick distributions and local abundance; 3) enzootic B. burgdorferi transmission cycles; and 4) Lyme disease cases. We conclude that meteorological variables are most influential in determining host-seeking phenology and development, but, while remaining important cofactors, additional variables become critical when exploring geographic distribution and local abundance of ticks, enzootic transmission of B. burgdorferi, and Lyme disease case occurrence. Finally, we review climate change-driven projections for future impact on vector ticks and Lyme disease and discuss knowledge gaps and research needs.

Septicemia and meningoencephalitis caused by Listeria monocytogenes in two neonatal llamas.

PubMed

Hawkins, Ian K; Ilha, Marcia; Anis, Eman; Wilkes, Rebecca P

2017-09-01

Listeriosis is a disease of humans and domestic mammals (mainly ruminants) with variable manifestations, primarily encephalitis, septicemia, and abortion. Although Listeria monocytogenes readily causes illness in ruminants, the prevalence among domestic South American camelids (llamas and alpacas) is low and has not been documented in their wild counterparts, the vicuna and guanaco. We describe herein the clinical signs, autopsy findings, and histopathology of septicemia and suppurative meningoencephalitis caused by L. monocytogenes in 2 neonatal llamas ( Llama glama) from the same herd. L. monocytogenes was isolated in pure culture and identified by real-time PCR on fresh and paraffin-embedded tissue samples of the brain from both crias. This presentation of septicemic listeriosis with meningoencephalitis in 2 animals from the same group is unusual, especially among llamas.

Systemic Lupus Erythematosus: A Review of the Clinical Approach to Diagnosis and Update on Current Targeted Therapies.

PubMed

Cunha, Joanne Szczygiel; Gilek-Seibert, Katarzyna

2016-12-01

Systemic lupus erythematosus (SLE) is a chronic, complicated and challenging disease to diagnose and treat. The etiology of SLE is unknown, but certain risk factors have been identified that lead to immune system dysfunction with antibody formation and immune complex deposition. This immune system dysregulation causes organ injury, contributing to the variable manifestations and relapsing-remitting course of the disease. Criteria were created to aide in the diagnosis, focusing on clinical manifestations and antibody profiles specific to SLE. Treatment options are limited to a few medications to control the inflammation and decrease organ damage. Continuing investigations into the pathogenesis of SLE has led to new discoveries, making more medications available to treat this difficult disease. [Full article available at http://rimed.org/rimedicaljournal-2016-12.asp].

From mild ataxia to huntington disease phenocopy: the multiple faces of spinocerebellar ataxia 17.

PubMed

Koutsis, Georgios; Panas, Marios; Paraskevas, George P; Bougea, Anastasia M; Kladi, Athina; Karadima, Georgia; Kapaki, Elisabeth

2014-01-01

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family.

From Mild Ataxia to Huntington Disease Phenocopy: The Multiple Faces of Spinocerebellar Ataxia 17

PubMed Central

Panas, Marios; Paraskevas, George P.; Bougea, Anastasia M.; Karadima, Georgia; Kapaki, Elisabeth

2014-01-01

Introduction. Spinocerebellar ataxia 17 (SCA 17) is a rare autosomal dominant cerebellar ataxia (ADCA) caused by a CAG/CAA expansion in the TBP gene, reported from a limited number of countries. It is a very heterogeneous ADCA characterized by ataxia, cognitive decline, psychiatric symptoms, and involuntary movements, with some patients presenting with Huntington disease (HD) phenocopies. The SCA 17 expansion is stable during parent-child transmission and intrafamilial phenotypic homogeneity has been reported. However, significant phenotypic variability within families has also been observed. Report of the Family. We presently report a Greek family with a pathological expansion of 54 repeats at the SCA 17 locus that displayed remarkable phenotypic variability. Among 3 affected members, one presented with HD phenocopy; one with progressive ataxia, dementia, chorea, dystonia, and seizures, and one with mild slowly progressive ataxia with minor cognitive and affective symptoms. Conclusions. This is the first family with SCA 17 identified in Greece and highlights the multiple faces of this rare disorder, even within the same family. PMID:25349749

One negative polysomnogram does not exclude obstructive sleep apnea.

PubMed

Meyer, T J; Eveloff, S E; Kline, L R; Millman, R P

1993-03-01

Night-to-night variability of apneas on overnight polymnography exists in patients with documented obstructive sleep apnea (OSA). In this study, we evaluated the possibility that this variability may be severe enough to miss the diagnosis of OSA in patients clinically at risk for the disease. We prospectively studied 11 patients who were deemed on clinical grounds to have probable OSA, but had a negative result on overnight polysomnography. Six of the 11 patients were found to have a positive second study with a significant rise in the apnea/hypopnea index (AHI) from 3.1 +/- 1.0 to 19.8 +/- 4.7 (mean +/- SEM, p < 0.01). The cause of the negative first study in these patients is unclear, but it does not seem related to risk factor pattern, sleep architecture, or test interval. The change in AHI was not found to be rapid eye movement (REM)-dependent. This study demonstrates that a negative first-night study is insufficient to exclude OSA in patients with one or more clinical markers of the disease.

Detection of time delays and directional interactions based on time series from complex dynamical systems

NASA Astrophysics Data System (ADS)

Ma, Huanfei; Leng, Siyang; Tao, Chenyang; Ying, Xiong; Kurths, Jürgen; Lai, Ying-Cheng; Lin, Wei

2017-07-01

Data-based and model-free accurate identification of intrinsic time delays and directional interactions is an extremely challenging problem in complex dynamical systems and their networks reconstruction. A model-free method with new scores is proposed to be generally capable of detecting single, multiple, and distributed time delays. The method is applicable not only to mutually interacting dynamical variables but also to self-interacting variables in a time-delayed feedback loop. Validation of the method is carried out using physical, biological, and ecological models and real data sets. Especially, applying the method to air pollution data and hospital admission records of cardiovascular diseases in Hong Kong reveals the major air pollutants as a cause of the diseases and, more importantly, it uncovers a hidden time delay (about 30-40 days) in the causal influence that previous studies failed to detect. The proposed method is expected to be universally applicable to ascertaining and quantifying subtle interactions (e.g., causation) in complex systems arising from a broad range of disciplines.

Characterization of Cardiopulmonary Exercise Testing Variables in Patients with Endomyocardial Fibrosis after Endocardial Resection

PubMed Central

Sayegh, Ana Luiza C.; dos Santos, Marcelo R.; de Oliveira, Patricia; Fernandes, Fábio; Rondon, Eduardo; de Souza, Francis R.; Salemi, Vera M. C.; Alves, Maria Janieire de N. N.; Mady, Charles

2017-01-01

Background Endomyocardial fibrosis (EMF) is a rare disease, characterized by diastolic dysfunction which leads to reduced peak oxygen consumption (VO2). Cardiopulmonary exercise testing (CPET) has been proved to be a fundamental tool to identify central and peripheral alterations. However, most studies prioritize peak VO2 as the main variable, leaving aside other important CPET variables that can specify the severity of the disease and guide the clinical treatment. Objective The aim of this study was to evaluate central and peripheral limitations in symptomatic patients with EMF by different CPET variables. Methods Twenty-six EMF patients (functional class III, NYHA) were compared with 15 healthy subjects (HS). Functional capacity was evaluated using CPET and diastolic and systolic functions were evaluated by echocardiography. Results Age and gender were similar between EMF patients and HS. Left ventricular ejection fraction was normal in EMF patients, but decreased compared to HS. Peak heart rate, peak workload, peak VO2, peak oxygen (O2) pulse and peak pulmonary ventilation (VE) were decreased in EMF compared to HS. Also, EMF patients showed increased Δ heart rate /Δ oxygen uptake and Δ oxygen uptake /Δ work rate compared to HS. Conclusion Determination of the aerobic capacity by noninvasive respiratory gas exchange during incremental exercise provides additional information about the exercise tolerance in patients with EMF. The analysis of different CPET variables is necessary to help us understand more about the central and peripheral alterations cause by both diastolic dysfunction and restrictive pattern. PMID:29364349

Gender-Specific Differences in All-Cause Mortality Between Incomplete and Complete Revascularization in Patients With ST-Elevation Myocardial Infarction and Multi-Vessel Coronary Artery Disease.

PubMed

Dimitriu-Leen, Aukelien C; Hermans, Maaike P J; van Rosendael, Alexander R; van Zwet, Erik W; van der Hoeven, Bas L; Bax, Jeroen J; Scholte, Arthur J H A

2018-03-01

The best revascularization strategy (complete vs incomplete revascularization) in patients with ST-elevation myocardial infarction (STEMI) is still debated. The interaction between gender and revascularization strategy in patients with STEMI on all-cause mortality is uncertain. The aim of the present study was to evaluate gender-specific difference in all-cause mortality between incomplete and complete revascularization in patients with STEMI and multi-vessel coronary artery disease. The study population consisted of 375 men and 115 women with a first STEMI and multi-vessel coronary artery disease without cardiogenic shock at admission or left main stenosis. The 30-day and 5-year all-cause mortality was examined in patients categorized according to gender and revascularization strategy (incomplete and complete revascularization). Within the first 30 days, men and women with incomplete revascularization were associated with higher mortality rates compared with men with complete revascularization. However, the gender-strategy interaction variable was not independently associated with 30-day mortality after STEMI when corrected for baseline characteristics and angiographic features. Within the survivors of the first 30 days, men with incomplete revascularization (compared with men with complete revascularization) were independently associated with all-cause mortality during 5 years of follow-up (hazard ratios 3.07, 95% confidence interval 1.24;7.61, p = 0.016). In contrast, women with incomplete revascularization were not independently associated with 5-year all-cause mortality (hazard ratios 0.60, 95% confidence interval 0.14;2.51, p = 0.48). In conclusion, no gender-strategy differences occurred in all-cause mortality within 30 days after STEMI. However, in the survivors of the first 30 days, incomplete revascularization in men was independently associated with all-cause mortality during 5-year follow-up, but this was not the case in women. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeting Wolman Disease and Cholesteryl Ester Storage Disease: Disease Pathogenesis and Therapeutic Development

PubMed Central

Aguisanda, Francis; Thorne, Natasha; Zheng, Wei

2017-01-01

Wolman disease (WD) and cholesteryl ester storage disease (CESD) are lysosomal storage diseases (LSDs) caused by a deficiency in lysosomal acid lipase (LAL) due to mutations in the LIPA gene. This enzyme is critical to the proper degradation of cholesterol in the lysosome. LAL function is completely lost in WD while some residual activity remains in CESD. Both are rare diseases with an incidence rate of less than 1/100,000 births for WD and approximate 2.5/100,000 births for CESD. Clinical manifestation of WD includes hepatosplenomegaly, calcified adrenal glands, severe malabsorption and a failure to thrive. As in CESD, histological analysis of WD tissues reveals the accumulation of triglycerides (TGs) and esterified cholesterol (EC) in cellular lysosomes. However, the clinical presentation of CESD is less severe and more variable than WD. This review is to provide an overview of the disease pathophysiology and the current state of therapeutic development for both of WD and CESD. The review will also discuss the application of patient derived iPSCs for further drug discovery. PMID:28401034

Malaria’s Indirect Contribution to All-Cause Mortality in the Andaman Islands during the Colonial Era

PubMed Central

Shanks, G. Dennis; Hay, Simon I.; Bradley, David J.

2009-01-01

Malaria appears to have a substantial secondary effect on other causes of mortality. From the 19th century, malaria epidemics in the Andaman Islands Penal Colony were initiated by the brackish swamp breeding malaria vector Anopheles sundaicus and fueled by the importation of new prisoners. Malaria was a major determinant of the highly variable all-cause mortality rate (correlation coefficient r2=0.60, n=68, p< 0.0001) from 1872 to 1939. Directly attributed malaria mortality based on postmortem examinations rarely exceeded one fifth of total mortality. Infectious diseases such as pneumonia, tuberculosis, dysentery and diarrhea, which combined with malaria made up a majority of all-cause mortality, were positively correlated to malaria incidence over several decades. Deaths secondary to malaria (indirect malaria mortality) were at least as great as mortality directly attributed to malaria infections. PMID:18599354

Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6.

PubMed

Rochester, Lynn; Galna, Brook; Lord, Sue; Mhiripiri, Dadirayi; Eglon, Gail; Chinnery, Patrick F

2014-02-01

Spinocerebellar ataxia type 6 (SCA6) is an inherited ataxia with no established treatment. Gait ataxia is a prominent feature causing substantial disability. Understanding the evolution of the gait disturbance is a key step in developing treatment strategies. We studied 9 gait variables in 24 SCA6 (6 presymptomatic; 18 symptomatic) and 24 controls and correlated gait with clinical severity (presymptomatic and symptomatic). Discrete gait characteristics precede symptoms in SCA6 with significantly increased variability of step width and step time, whereas a more global gait deficit was evident in symptomatic individuals. Gait characteristics discriminated between presymptomatic and symptomatic individuals and were selectively associated with disease severity. This is the largest study to include a detailed characterization of gait in SCA6, including presymptomatic subjects, allowing changes across the disease spectrum to be compared. Selective gait disturbance is already present in SCA6 before clinical symptoms appear and gait characteristics are also sensitive to disease progression. Early gait disturbance likely reflects primary pathology distinct from secondary changes. These findings open the opportunity for early evaluation and sensitive measures of therapeutic efficacy using instrumented gait analysis which may have broader relevance for all degenerative ataxias. © 2013 Movement Disorder Society.

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.

Regression dilution bias: tools for correction methods and sample size calculation.

PubMed

Berglund, Lars

2012-08-01

Random errors in measurement of a risk factor will introduce downward bias of an estimated association to a disease or a disease marker. This phenomenon is called regression dilution bias. A bias correction may be made with data from a validity study or a reliability study. In this article we give a non-technical description of designs of reliability studies with emphasis on selection of individuals for a repeated measurement, assumptions of measurement error models, and correction methods for the slope in a simple linear regression model where the dependent variable is a continuous variable. Also, we describe situations where correction for regression dilution bias is not appropriate. The methods are illustrated with the association between insulin sensitivity measured with the euglycaemic insulin clamp technique and fasting insulin, where measurement of the latter variable carries noticeable random error. We provide software tools for estimation of a corrected slope in a simple linear regression model assuming data for a continuous dependent variable and a continuous risk factor from a main study and an additional measurement of the risk factor in a reliability study. Also, we supply programs for estimation of the number of individuals needed in the reliability study and for choice of its design. Our conclusion is that correction for regression dilution bias is seldom applied in epidemiological studies. This may cause important effects of risk factors with large measurement errors to be neglected.

Structural and Functional Studies on the Fusion and Attachment Envelope Glycoproteins of Nipah Virus and Hendra Virus

DTIC Science & Technology

2003-01-01

epidemics, caused by Vibrio cholerae have been linked to specific seasons and biogeographical zones. In addition, the population dynamics of V. cholerae in...Climactic warming has directly affected the prevalence of RVFV by prolonging survival rates of the vector involved in disease transmission. 3 Cholera ...climate variability. The study of V. cholerae represents a model system of how climate change affects pathogens (2). Personal human behavior has

Subacute sclerosing panencephalitis in immunized Thai children.

PubMed

Khusiwilai, Khanittha; Viravan, Sorawit

2011-12-01

Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease with high mortality and poor prognosis. This is caused by persistent defective measles virus infection. Clinical presentations are variable including behavioral-cognitive change, myoclonic seizure, visual problem, spasticity or abnormal movement. The authors report a case of 10 year-old boy, previously healthy with complete immunization, presenting with frequent myoclonic jerks, abnormal movements, spasticity and altered mental status. Electroencephalographic (EEG), magnetic resonance imaging (MRI), and laboratory findings are typical for SSPE.

Pharmacogenetic studies in Alzheimer disease.

PubMed

Zúñiga Santamaría, T; Yescas Gómez, P; Fricke Galindo, I; González González, M; Ortega Vázquez, A; López López, M

2018-06-10

Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response. We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial. Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as aging. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Cystic fibrosis: a clinical view.

PubMed

Castellani, Carlo; Assael, Baroukh M

2017-01-01

Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude. Classical treatment includes pancreatic enzyme replacement, respiratory physiotherapy, mucolitics, and aggressive antibiotic therapy. A significant proportion of patients with severe symptoms still requires lung or, less frequently, liver transplantation. The great number of mutations and their diverse effects on the CFTR protein account only partially for CF clinical variability, and modifier genes have a role in modulating the clinical expression of the disease. Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder. Research is focusing on new drugs restoring CFTR function, some already available and with good clinical impact, others showing promising preliminary results that need to be confirmed in phase III clinical trials.

Foodborne Salmonella-caused outbreaks in Catalonia (Spain), 1990 to 2003.

PubMed

Domínguez, Angela; Torner, Nuria; Ruiz, Laura; Martínez, Ana; Bartolomé, Rosa; Sulleiro, Elena; Teixidó, Angel; Plasencia, Antoni

2007-01-01

In most developed countries, nontyphoid Salmonella is an important cause of sporadic cases and outbreaks of foodborne gastroenteritis. The aim of this study was to investigate the trend of foodborne Salmonella-caused outbreaks and number of cases, hospitalizations, and deaths and compare them with those caused by other infectious agents. The study was carried out in Catalonia, a region in northeastern Spain with a population of 6.5 million inhabitants, in 2002. All information on reported outbreaks of foodborne disease from 1990 to 2003 was reviewed. For each outbreak, the following variables were collected: year; setting (household, restaurant, school, hospital, nursing home, and others); number of cases, hospitalizations, and deaths; causal agent; and food vehicle involved. Of 1652 reported outbreaks, 1078 had a known causal agent. Among them, 871 (80.8%) were caused by Salmonella, with 14,695 cases, 1534 hospitalizations, and 4 deaths. The rate of hospitalization was higher in outbreaks due to Salmonella than in those caused by other infectious agents (rate ratio, 2.54; 95% confidence interval, 2.20 to 2.94). Forty-eight percent of Salmonella-caused outbreaks were eggborne, compared with 5.3% of those caused by other infectious agents (rate ratio, 1.40; 95% confidence interval, 1.33 to 1.48). The annual number of cases in household outbreaks of eggborne Salmonella rose over time (R2 = 0.82), but the number of outbreaks produced in other settings did not. Eggborne outbreaks caused by Salmonella in households are a major cause of disease, and increased preventive efforts are necessary, especially consumer education and awareness of the risk of eating food containing raw or slightly cooked eggs.

Feline leprosy due to Candidatus 'Mycobacterium lepraefelis': Further clinical and molecular characterisation of eight previously reported cases and an additional 30 cases.

PubMed

O'Brien, Carolyn R; Malik, Richard; Globan, Maria; Reppas, George; McCowan, Christina; Fyfe, Janet A

2017-09-01

This paper, the last in a series of three on 'feline leprosy', provides a detailed description of disease referable to the previously unnamed species, Candidatus 'Mycobacterium lepraefelis', a close relative of the human pathogens Mycobacterium leprae and Mycobacterium lepromatosis. Cases were sourced retrospectively and prospectively for this observational study, describing clinical, geographical and molecular microbiological data for cats definitively diagnosed with Candidatus 'M lepraefelis' infection. A total of 145 cases of feline leprosy were scrutinised; 114 'new' cases were sourced from the Victorian Infectious Diseases Reference Laboratory (VIDRL) records, veterinary pathology laboratories or veterinarians, and 31 cases were derived from six published studies. Thirty-eight cats were definitively diagnosed with Candidatus 'M lepraefelis' infection. Typically, cats tended to be middle-aged or older when first infected, with a male predilection. Affected cats typically had widespread cutaneous lesions, in some cases after initially localised disease. Advanced cases were often systemically unwell. All cats had outdoor access. The histological picture was lepromatous in the majority of patients, although two cases had tuberculoid disease. In one case that underwent necropsy, lesions were evident in the liver, spleen and lungs. Treatment was varied, although most cats received a combination of oral clarithromycin and rifampicin. Prognosis for recovery was variable, but typically poor. Candidatus 'M lepraefelis' typically causes high bacterial index (lepromatous) feline leprosy that in some cases progresses to systemic mycobacteriosis. The disease has a variable clinical course and prognosis. Many cases either died or were euthanased due to the infection. Multilocus sequence analysis reveals a heterogeneous picture and further analysis of draft genome sequencing may give clues to the taxonomy and epidemiology of this organism. Prospective treatment trials and/or additional drug susceptibility testing in specialised systems would further inform treatment recommendations. Comparative aspects: This paper finishes with a discussion of comparative aspects of infection caused by the three feline leproid disease agents that have been the subject of this series: Candidatus 'Mycobacterium tarwinense', Mycobacterium lepraemurium and Candidatus 'M lepraefelis'.

MYH9 genetic variants associated with glomerular disease: what is the role for genetic testing?

PubMed

Kopp, Jeffrey B; Winkler, Cheryl A; Nelson, George W

2010-07-01

Genetic variation in MYH9, encoding nonmuscle myosin IIA heavy chain, has been associated recently with increased risk for kidney disease. Previously, MYH9 missense mutations have been shown to cause the autosomal-dominant MYH9 (ADM9) spectrum, characterized by large platelets, leukocyte Döhle bodies, and, variably, sensorineural deafness, cataracts, and glomerulopathy. Genetic testing is indicated for familial and sporadic cases that fit this spectrum. By contrast, the MYH9 kidney risk variant is characterized by multiple intronic single nucleotide polymorphisms, but the causative variant has not been identified. Disease associations include human immunodeficiency virus-associated collapsing glomerulopathy, focal segmental glomerulosclerosis, hypertension-attributed end-stage kidney disease, and diabetes-attributed end-stage kidney disease. One plausible hypothesis is that the MYH9 kidney risk variant confers a fragile podocyte phenotype. In the case of hypertension-attributed kidney disease, it remains unclear if the hypertension is a contributing cause or a consequence of glomerular injury. The MYH9 kidney risk variant is strikingly more common among individuals of African descent, but only some will develop clinical kidney disease in their lifetime. Thus, it is likely that additional genes and/or environmental factors interact with the MYH9 kidney risk variant to trigger glomerular injury. A preliminary genetic risk stratification scheme, using two single nucleotide polymorphisms, may estimate lifetime risk for kidney disease. Nevertheless, at present, no role has been established for genetic testing as part of personalized medicine, but testing should be considered in clinical studies of glomerular diseases among populations of African descent. Such studies will address critical questions pertaining to MYH9-associated kidney disease, including mechanism, course, and response to therapy. Published by Elsevier Inc.

Climate change and vector-borne diseases: what are the implications for public health research and policy?

PubMed

Campbell-Lendrum, Diarmid; Manga, Lucien; Bagayoko, Magaran; Sommerfeld, Johannes

2015-04-05

Vector-borne diseases continue to contribute significantly to the global burden of disease, and cause epidemics that disrupt health security and cause wider socioeconomic impacts around the world. All are sensitive in different ways to weather and climate conditions, so that the ongoing trends of increasing temperature and more variable weather threaten to undermine recent global progress against these diseases. Here, we review the current state of the global public health effort to address this challenge, and outline related initiatives by the World Health Organization (WHO) and its partners. Much of the debate to date has centred on attribution of past changes in disease rates to climate change, and the use of scenario-based models to project future changes in risk for specific diseases. While these can give useful indications, the unavoidable uncertainty in such analyses, and contingency on other socioeconomic and public health determinants in the past or future, limit their utility as decision-support tools. For operational health agencies, the most pressing need is the strengthening of current disease control efforts to bring down current disease rates and manage short-term climate risks, which will, in turn, increase resilience to long-term climate change. The WHO and partner agencies are working through a range of programmes to (i) ensure political support and financial investment in preventive and curative interventions to bring down current disease burdens; (ii) promote a comprehensive approach to climate risk management; (iii) support applied research, through definition of global and regional research agendas, and targeted research initiatives on priority diseases and population groups. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

VEGFA polymorphisms and cardiovascular anomalies in 22q11 microdeletion syndrome: a case-control and family-based study.

PubMed

Calderón, Juan Francisco; Puga, Alonso R; Guzmán, M Luisa; Astete, Carmen Paz; Arriaza, Marta; Aracena, Mariana; Aravena, Teresa; Sanz, Patricia; Repetto, Gabriela M

2009-01-01

Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes. Most patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous. Congenital heart disease is present in 50-80% of patients and is a significant cause of morbidity and mortality. The phenotypic variability suggests the presence of modifiers. Polymorphisms in the VEGFA gene, coding for the vascular endothelial growth factor A, have been associated with non-syndromic congenital heart disease, as well as with the presence of cardiovascular anomalies in patients with microdeletion 22q11. We evaluated the association of VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G (rs2010963) with congenital heart disease in Chilean patients with microdeletion 22q11. The study was performed using case-control and family-based association designs. We evaluated 122 patients with microdeletion 22q11 and known anatomy of the heart and great vessels, and their parents. Half the patients had congenital heart disease. We obtained no evidence of association by either method of analysis. Our results provide further evidence of the incomplete penetrance of the cardiovascular phenotype of microdeletion 22ql 1, but do not support association between VEGFA promoter polymorphisms and the presence of congenital heart disease in Chilean patients with this syndrome.

Activating mutations affecting the Dbl homology domain of SOS2 cause Noonan syndrome

PubMed Central

Cordeddu, Viviana; Yin, Jiani C.; Gunnarsson, Cecilia; Virtanen, Carl; Drunat, Séverine; Lepri, Francesca; De Luca, Alessandro; Rossi, Cesare; Ciolfi, Andrea; Pugh, Trevor J.; Bruselles, Alessandro; Priest, James R.; Pennacchio, Len A.; Lu, Zhibin; Danesh, Arnavaz; Quevedo, Rene; Hamid, Alaa; Martinelli, Simone; Pantaleoni, Francesca; Gnazzo, Maria; Daniele, Paola; Lissewski, Christina; Bocchinfuso, Gianfranco; Stella, Lorenzo; Odent, Sylvie; Philip, Nicole; Faivre, Laurence; Vlckova, Marketa; Seemanova, Eva; Digilio, Cristina; Zenker, Martin; Zampino, Giuseppe; Verloes, Alain; Dallapiccola, Bruno; Roberts, Amy E.; Cavé, Hélène; Gelb, Bruce D.; Neel, Benjamin G.; Tartaglia, Marco

2015-01-01

The RASopathies constitute a family of autosomal dominant disorders whose major features include facial dysmorphism, cardiac defects, reduced postnatal growth, variable cognitive deficits, ectodermal and skeletal anomalies, and susceptibility to certain malignancies. Noonan syndrome (NS), the commonest RASopathy, is genetically heterogeneous and caused by functional dysregulation of signal transducers and regulatory proteins with roles in the RAS/extracellular signal-regulated kinase (ERK) signal transduction pathway. Mutations in known disease genes account for approximately 80% of affected individuals. Here, we report that missense mutations altering son of sevenless, Drosophila, homolog 2 (SOS2), which encodes a RAS guanine nucleotide exchange factor, occur in a small percentage of subjects with NS. Four missense mutations were identified in five unrelated sporadic cases and families transmitting NS. Disease-causing mutations affected three conserved residues located in the Dbl homology domain, of which two are directly involved in the intramolecular binding network maintaining SOS2 in its auto-inhibited conformation. All mutations were found to promote enhanced signaling from RAS to ERK. Similar to NS-causing SOS1 mutations, the phenotype associated with SOS2 defects is characterized by normal development and growth, as well as marked ectodermal involvement. Unlike SOS1 mutations, however, those in SOS2 are restricted to the Dbl homology domain. PMID:26173643

Integrating in silico prediction methods, molecular docking, and molecular dynamics simulation to predict the impact of ALK missense mutations in structural perspective.

PubMed

Doss, C George Priya; Chakraborty, Chiranjib; Chen, Luonan; Zhu, Hailong

2014-01-01

Over the past decade, advancements in next generation sequencing technology have placed personalized genomic medicine upon horizon. Understanding the likelihood of disease causing mutations in complex diseases as pathogenic or neutral remains as a major task and even impossible in the structural context because of its time consuming and expensive experiments. Among the various diseases causing mutations, single nucleotide polymorphisms (SNPs) play a vital role in defining individual's susceptibility to disease and drug response. Understanding the genotype-phenotype relationship through SNPs is the first and most important step in drug research and development. Detailed understanding of the effect of SNPs on patient drug response is a key factor in the establishment of personalized medicine. In this paper, we represent a computational pipeline in anaplastic lymphoma kinase (ALK) for SNP-centred study by the application of in silico prediction methods, molecular docking, and molecular dynamics simulation approaches. Combination of computational methods provides a way in understanding the impact of deleterious mutations in altering the protein drug targets and eventually leading to variable patient's drug response. We hope this rapid and cost effective pipeline will also serve as a bridge to connect the clinicians and in silico resources in tailoring treatments to the patients' specific genotype.

Respiratory syncytial virus infection in cattle.

PubMed

Sacco, R E; McGill, J L; Pillatzki, A E; Palmer, M V; Ackermann, M R

2014-03-01

Bovine respiratory syncytial virus (RSV) is a cause of respiratory disease in cattle worldwide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV infection can predispose calves to secondary bacterial infection by organisms such as Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, resulting in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Even in cases where animals do not succumb to bovine respiratory disease complex, there can be long-term losses in production performance. This includes reductions in feed efficiency and rate of gain in the feedlot, as well as reproductive performance, milk production, and longevity in the breeding herd. As a result, economic costs to the cattle industry from bovine respiratory disease have been estimated to approach $1 billion annually due to death losses, reduced performance, and costs of vaccinations and treatment modalities. Human and bovine RSV are closely related viruses with similarities in histopathologic lesions and mechanisms of immune modulation induced following infection. Therefore, where appropriate, we provide comparisons between RSV infections in humans and cattle. This review article discusses key aspects of RSV infection of cattle, including epidemiology and strain variability, clinical signs and diagnosis, experimental infection, gross and microscopic lesions, innate and adaptive immune responses, and vaccination strategies.

Metabolic cutis laxa syndromes.

PubMed

Mohamed, Miski; Kouwenberg, Dorus; Gardeitchik, Thatjana; Kornak, Uwe; Wevers, Ron A; Morava, Eva

2011-08-01

Cutis laxa is a rare skin disorder characterized by wrinkled, redundant, inelastic and sagging skin due to defective synthesis of elastic fibers and other proteins of the extracellular matrix. Wrinkled, inelastic skin occurs in many cases as an acquired condition. Syndromic forms of cutis laxa, however, are caused by diverse genetic defects, mostly coding for structural extracellular matrix proteins. Surprisingly a number of metabolic disorders have been also found to be associated with inherited cutis laxa. Menkes disease was the first metabolic disease reported with old-looking, wrinkled skin. Cutis laxa has recently been found in patients with abnormal glycosylation. The discovery of the COG7 defect in patients with wrinkled, inelastic skin was the first genetic link with the Congenital Disorders of Glycosylation (CDG). Since then several inborn errors of metabolism with cutis laxa have been described with variable severity. These include P5CS, ATP6V0A2-CDG and PYCR1 defects. In spite of the evolving number of cutis laxa-related diseases a large part of the cases remain genetically unsolved. In metabolic cutis laxa syndromes the clinical and laboratory features might partially overlap, however there are some distinct, discriminative features. In this review on metabolic diseases causing cutis laxa we offer a practical approach for the differential diagnosis of metabolic cutis laxa syndromes.

Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

PubMed

Varbo, Anette; Benn, Marianne; Smith, George Davey; Timpson, Nicholas J; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

2015-02-13

Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss. © 2014 American Heart Association, Inc.

[TREATMENT DILEMMAS IN BEHÇET'S SYNDROME].

PubMed

Zeller, Lior; Ling, Edoard; Abu-Shakra, Mahmoud

2016-02-01

Behçet's disease is an inflammatory systemic disorder, characterized by a relapsing and remitting course, it manifests with oral and genital ulcerations, skin lesions, uveitis, vasculitis, central nervous system and gastrointestinal involvement. The main histopathological finding is widespread vasculitis of the arteries and veins. Therapy is variable and depends largely on the severity of the disease and organ involvement. There is common practice to treat with anticoagulation in patients suffering from vessel thrombosis, but there are no control trials to support this tendency. Anticoagulation treatment can cause major bleeding events in patients suffering from aneurysms. In this case report we describe a treatment dilemma in a patient suffering from deep vein thrombosis and pulmonary aneurysms.

The role of Epstein-Barr virus in systemic lupus erythematosus.

PubMed

McClain, M T; Harley, J B; James, J A

2001-10-01

Systemic lupus erythematosus (SLE) is a devastating autoimmune disease with no known cure. Lupus patients suffer from a myriad of clinical symptoms which variably include arthritis, pleuritis, pericarditis, vasculitis, and nephritis. The underlying mechanisms behind these clinical findings and the etiologic events preceding and causing disease onset, however, remain largely unknown. For many years, investigators have suspected that Epstein-Barr virus might somehow be involved in the etiology and/or pathogenesis of systemic lupus. Numerous studies have examined this possibility from various angles and have arrived at different conclusions. This work reviews these historical papers in the context of new results and presents a hypothetical role for this virus as an etiological environmental trigger for SLE.

Multifocal Epithelial Hyperplasia of Oral Cavity Expressing HPV 16 Gene: A Rare Entity

PubMed Central

Prabhat, M. P. V.; Raja Lakshmi, Chintamaneni; Sai Madhavi, N.; Bhavana, Sujana Mulk; Sarat, Gummadapu; Ramamohan, Kodali

2013-01-01

Focal epithelial hyperplasia is a rare contagious disease caused by human papilloma virus. Usually HPV involves either cutaneous or mucosal surfaces, whereas concomitant mucocutaneous involvement is extremely rare. We report such a unique case of multifocal epithelial hyperplasia involving multiple sites of oral cavity along with skin lesions in a 65-year-old female. We also discuss the probable multifactorial etiology and variable clinical presentations of the lesions, including evidence of HPV 16 expression, as detected by polymerase chain reaction. The present report illustrates the need for careful examination and prompt diagnosis of the disease, as it might be associated with high risk genotypes such as HPV 16 and 18. PMID:24455323

Pharmacokinetic drug evaluation of safinamide mesylate for the treatment of mid-to-late stage Parkinson's disease.

PubMed

Müller, Thomas

2017-06-01

Patients with Parkinson's disease suffer from a heterogeneous expression of neurotransmitter deficits. They cause an individual variable expression of motor and non-motor symptoms. Thus, drugs with various mechanisms of actions are suitable to counteract these disease related neurotransmitter alterations. Areas covered: This invited review suggests safinamide as an ideal compound for therapy of Parkinson's disease, as its pharmacological profile includes reversible monoamine oxidase B inhibition, blockage of voltage-dependent sodium channels, modulation of calcium channels and abnormal glutamate release. Safinamide may provide benefits effects on non-motor symptoms in addition to the demonstrated amelioration of motor impairment in levodopa treated patients with Parkinson's disease. Safinamide was well tolerated and safe when administered in dose of 50 or 100 mg daily in pivotal trials. Expert opinion: Clinical handling, safety and tolerability of Safinamide are better than of dopamine agonists or levodopa. Safinamide supplements the existing armamentarium of drugs for Parkinson's disease. Safinamide will help to reduce dosing of levodopa but also of dopamine agonists during long term treatment in patients with Parkinson's disease.

Land use, macroalgae, and a tumor-forming disease in marine turtles.

PubMed

Van Houtan, Kyle S; Hargrove, Stacy K; Balazs, George H

2010-09-29

Wildlife diseases are an increasing concern for endangered species conservation, but their occurrence, causes, and human influences are often unknown. We analyzed 3,939 records of stranded Hawaiian green sea turtles (Chelonia mydas) over 28 years to understand fibropapillomatosis, a tumor-forming disease linked to a herpesvirus. Turtle size is a consistent risk factor and size-standardized models revealed considerable spatial and temporal variability. The disease peaked in some areas in the 1990s, in some regions rates remained constant, and elsewhere rates increased. Land use, onshore of where the turtles feed, may play a role. Elevated disease rates were clustered in watersheds with high nitrogen-footprints; an index of natural and anthropogenic factors that affect coastal eutrophication. Further analysis shows strong epidemiological links between disease rates, nitrogen-footprints, and invasive macroalgae and points to foraging ecology. These turtles now forage on invasive macroalgae, which can dominate nutrient rich waters and sequester environmental N in the amino acid arginine. Arginine is known to regulate immune activity, promote herpesviruses, and contribute to tumor formation. Our results have implications for understanding diseases in aquatic organisms, eutrophication, herpesviruses, and tumor formation.

Rural/urban mortality differences in England and Wales and the effect of deprivation adjustment.

PubMed

Gartner, Andrea; Farewell, Daniel; Roach, Paul; Dunstan, Frank

2011-05-01

Perceptions that rural populations are inevitably healthier and live longer than urban populations are increasingly being challenged. But very few publications have investigated the extent to which these putative differences can be explained by variation in area composition. Existing publications have tended to use conventional deprivation measures, often thought to mask rural deprivation by favourable averages. Further, they have typically been based on large and variably-sized geographical units, or confined to studies of a single region or cause of death. This study examines differences in mortality between rural and urban areas in the entire population of England and Wales for 2002-2004. It uses the most up-to-date small geographical units of similar size and homogeneity of population together with the recently-introduced Rural and Urban Area Classification, and adjusts for five different deprivation measures (including modern composite indices). The causes of death investigated were all-cause mortality, cancer, lung cancer, respiratory disease, circulatory disease, suicide and accidents. Particular points of focus for the study were the potential for interaction between deprivation and rurality, and the importance of choice of deprivation measure in quantifying the relationships between mortality, rurality and deprivation. Choice of deprivation measure was not found to alter the substantive conclusions of any analysis, and little evidence for differential effects of deprivation in rural and urban areas was uncovered. Differences between rural and urban areas in all-cause, circulatory disease and cancer mortality could largely be accounted for by adjusting for deprivation. For these causes of death, therefore, rural populations were not found to be inherently healthier than their urban counterparts. However, substantial residual differences between rural and urban areas were found in comparisons of mortality from lung cancer and respiratory disease, mortality being lower in rural areas. Stronger relationships between rurality and mortality were found in 'village and dispersed' settlements. Copyright © 2011 Elsevier Ltd. All rights reserved.

Myasthenia and related disorders of the neuromuscular junction.

PubMed

Spillane, Jennifer; Beeson, David J; Kullmann, Dimitri M

2010-08-01

Our understanding of transmission at the neuromuscular junction has increased greatly in recent years. We now recognise a wide variety of autoimmune and genetic diseases that affect this specialised synapse, causing muscle weakness and fatigue. These disorders greatly affect quality of life and rarely can be fatal. Myasthenia gravis is the most common disorder and is most commonly caused by autoantibodies targeting postsynaptic acetylcholine receptors. Antibodies to muscle-specific kinase (MuSK) are detected in a variable proportion of the remainder. Treatment is symptomatic and immunomodulatory. Lambert-Eaton myasthenic syndrome is caused by antibodies to presynaptic calcium channels, and approximately 50% of cases are paraneoplastic, most often related to small cell carcinoma of the lung. Botulism is an acquired disorder caused by neurotoxins produced by Clostridium botulinum, impairing acetylcholine release into the synaptic cleft. In addition, several rare congenital myasthenic syndromes have been identified, caused by inherited defects in presynaptic, synaptic basal lamina and postsynaptic proteins necessary for neuromuscular transmission. This review focuses on recent advances in the diagnosis and treatment of these disorders.

Ventricular Diastolic Function in Normal Fetuses and Fetuses with Hb Bart's Disease Assessed by Color M-Mode Propagation Velocity using Cardio-STIC-M (Spatio-Temporal Image Correlation M-Mode).

PubMed

Tongsong, T; Tongprasert, F; Srisupundit, K; Luewan, S; Traisrisilp, K

2016-10-01

Purpose: To determine whether ventricular diastolic dysfunction contributes to the pathogenesis of fetal cardiac failure due to fetal anemia using fetal Hb Bart's disease as a live model and cardio-STIC-M as a diagnostic tool. Materials and Methods: Color cardio-STIC volume datasets were acquired from fetuses at risk for Hb Bart's disease during 18 - 22 weeks of gestation and normal pregnancies and pregnancies with hydrops fetalis caused by Hb Bart's disease at 28 - 32 weeks. The volumes were analyzed off-line for velocity propagation (Vp) of the right and left ventricles to assess ventricular diastolic function using color cardio-STIC-M. Results: The Vp for the right and left ventricles was studied in fetuses at 18 - 22 weeks, including 64 normal fetuses (group 1) and 22 fetuses with Hb Bart's disease (group 2), and in fetuses at 28 - 32 weeks, including 22 normal fetuses (group 3) and 16 fetuses with Hb Bart's hydrops fetalis (group 4). The Vp of the fetuses in group 1 and group 2 was not significantly different. However, the Vp for the right and left ventricles in group 4 was significantly lower than in group 3 (19.02 vs. 9.78, p < 0.001; and 20.24 vs. 13.40, p < 0.001, respectively). The inter-observer variability had fair agreement with the intra-class correlation coefficient of 0.531 (95 % CI 0.393 - 0.646, p < 0.001). Conclusion: Hydrops fetalis secondary to fetal anemia is initially caused by hypervolemia rather than ventricular diastolic dysfunction while ventricular diastolic compromise is a late occurring consequence of persistent hypervolemia, different from the mechanism of hydropic changes caused by cardiac causes. © Georg Thieme Verlag KG Stuttgart · New York.

[Diagnosis and treatment of Pompe disease].

PubMed

Bravo-Oro, Antonio; de la Fuente-Cortez, Beatriz; Molina-García, Avril; Romero-Díaz, Víktor; Rodríguez-Leyva, Ildefonso; Esmer-Sánchez, María del Carmen

2013-01-01

Pompe disease is a rare, progressive and often fatal neuromuscular disorder. It is caused by a deficiency of the lysosomal alpha-glucosidase. Among glycogen storage disorders, it is one of the most common. Its clinical manifestations can start at any moment of life, with a very variable symptomatology. In this article, we show an extended revision of the literature in regards to the main medical aspects of Pompe disease: etiology, psychopathology, epidemiology, clinical variants, pathological diagnosis, and enzyme replacement therapy. With this information, we created a diagnostic and therapeutic guide, which is addressed to specialists and to first-level physicians, in order to let them identify both the classic and the late forms of this disease. We describe as well the best, timely, multidisciplinary treatment in use. Also, we show some suggestions to the proper functioning of health institutions, and routes to diagnosis. We conclude that Pompe disease may be properly diagnosed and treated if health care professionals follow the internationally approved recommendations.

Case−Control Study of Risk Factors for Meningococcal Disease in Chile

PubMed Central

Matute, Isabel; González, Claudia; Delgado, Iris; Poffald, Lucy; Pedroni, Elena; Alfaro, Tania; Hirmas, Macarena; Nájera, Manuel; Gormaz, Ana; López, Darío; Loayza, Sergio; Ferreccio, Catterina; Gallegos, Doris; Fuentes, Rodrigo; Vial, Pablo; Aguilera, Ximena

2017-01-01

An outbreak of meningococcal disease with a case-fatality rate of 30% and caused by predominantly serogroup W of Neisseria meningitidis began in Chile in 2012. This outbreak required a case−control study to assess determinants and risk factors for infection. We identified confirmed cases during January 2012−March 2013 and selected controls by random sampling of the population, matched for age and sex, resulting in 135 case-patients and 618 controls. Sociodemographic variables, habits, and previous illnesses were studied. Analyses yielded adjusted odds ratios as estimators of the probability of disease development. Results indicated that conditions of social vulnerability, such as low income and overcrowding, as well as familial history of this disease and clinical histories, especially chronic diseases and hospitalization for respiratory conditions, increased the probability of illness. Findings should contribute to direction of intersectoral public policies toward a highly vulnerable social group to enable them to improve their living conditions and health. PMID:28628448

Important role of translational science in rare disease innovation, discovery, and drug development.

PubMed

Pariser, Anne R; Gahl, William A

2014-08-01

Rare diseases play a leading role in innovation and the advancement of medical and pharmaceutical science. Most rare diseases are genetic disorders or atypical manifestations of infectious, immunologic, or oncologic diseases; they all provide opportunities to study extremes of human pathology and provide insight into both normal and aberrant physiology. Recently, drug development has become increasingly focused on classifying diseases largely on genetic grounds; this has allowed the identification of molecularly defined targets and the development of targeted therapies. Clinical trials are now focusing on progressively smaller subgroups within both common and rare disease populations, often based on genetic tests or biomarkers. Drug developers, researchers, and regulatory agencies face a variety of challenges throughout the life cycle of drug research and development for rare diseases. These include the small numbers of patients available for study, lack of knowledge of the disease's natural history, incomplete understanding of the basic mechanisms causing the disorder, and variability in disease severity, expression, and course. Traditional approaches to rare disease clinical research have not kept pace with advances in basic science, and increased attention to translational science is needed to address these challenges, especially diagnostic testing, registries, and novel trial designs.

Official Positions for FRAX® clinical regarding rheumatoid arthritis from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

PubMed

Broy, Susan B; Tanner, S Bobo

2011-01-01

Rheumatoid arthritis is the only secondary cause of osteoporosis that is considered independent of bone density in the FRAX(®) algorithm. Although input for rheumatoid arthritis in FRAX(®) is a dichotomous variable, intuitively, one would expect that more severe or active disease would be associated with a greater risk for fracture. We reviewed the literature to determine if specific disease parameters or medication use could be used to better characterize fracture risk in individuals with rheumatoid arthritis. Although many studies document a correlation between various parameters of disease activity or severity and decreased bone density, fewer have associated these variables with fracture risk. We reviewed these studies in detail and concluded that disability measures such as HAQ (Health Assessment Questionnaire) and functional class do correlate with clinical fractures but not morphometric vertebral fractures. One large study found a strong correlation with duration of disease and fracture risk but additional studies are needed to confirm this. There was little evidence to correlate other measures of disease such as DAS (disease activity score), VAS (visual analogue scale), acute phase reactants, use of non-glucocorticoid medications and increased fracture risk. We concluded that FRAX(®) calculations may underestimate fracture probability in patients with impaired functional status from rheumatoid arthritis but that this could not be quantified at this time. At this time, other disease measures cannot be used for fracture prediction. However only a few, mostly small studies addressed other disease parameters and further research is needed. Additional questions for future research are suggested. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

WDR73 missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in a consanguineous family.

PubMed

Jiang, Chen; Gai, Nan; Zou, Yongyi; Zheng, Yu; Ma, Ruiyu; Wei, Xianda; Liang, Desheng; Wu, Lingqian

2017-01-01

Galloway-Mowat syndrome (GMS) is a very rare autosomal-recessive disorder characterized by nephrotic syndrome associated with microcephaly, and various central nervous system abnormalities, mostly cerebral hypoplasia or cerebellar atrophy, intellectual disability and neural-migration defects. WDR73 is the only gene known to cause GMS, and has never been implicated in other disease. Here we present a Chinese consanguineous family with infantile onset intellectual disability and cerebellar hypoplasia but no microcephaly. Whole exome sequencing identified a WDR73 p.W371G missense mutation. The mutation is confirmed to be segregated in this family by Sanger sequencing according to a recessive inheritance pattern. It is predicted to be deleterious by multiple algorithms and affect highly conserved site. Structural modeling revealed conformational differences between the wild type protein and the p.W371G protein. Real-time PCR and Western blotting revealed altered mRNA and protein levels in mutated samples. Our study indicates the novel WDR73 p.W371G missense mutation causes infantile onset intellectual disability and cerebellar hypoplasia in recessive mode of inheritance. Our findings imply that microcephaly is a variable phenotype in WDR73-related disease, suggest WDR73 to be a candidate gene of severe intellectual disability and cerebellar hypoplasia, and expand the molecular spectrum of WDR73-related disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Thyroid disorders and gastrointestinal and liver dysfunction: A state of the art review.

PubMed

Kyriacou, Angelos; McLaughlin, John; Syed, Akheel A

2015-10-01

Thyroid disorders commonly impact on the gastrointestinal system and may even present with gastrointestinal symptoms in isolation; for example, metastatic medullary thyroid carcinoma typically presents with diarrhoea. Delays in identifying and treating the underlying thyroid dysfunction may lead to unnecessary investigations and treatment, with ongoing morbidity, and can potentially be life-threatening. Similarly, gastrointestinal diseases can impact on thyroid function tests, and an awareness of the concept and management of non-thyroidal illness is necessary to avoid giving unnecessary thyroid therapies that could potentially exacerbate the underlying gastrointestinal disease. Dual thyroid and gastrointestinal pathologies are also common, with presentations occurring concurrently or sequentially, the latter after a variable time lag that can even extend over decades. Such an association aetiologically relates to the autoimmune background of many thyroid disorders (e.g. Graves' disease and Hashimoto's thyroiditis) and gastrointestinal disorders (e.g. coeliac disease and inflammatory bowel disease); such autoimmune conditions can sometimes occur in the context of autoimmune polyglandular syndrome. Emphasis should also be given to the gastrointestinal side effects of some of the medications used for thyroid disease (e.g. anti-thyroid drugs causing hepatotoxicity) and vice versa (e.g. interferon therapy causing autoimmune thyroid dysfunction). In this review, we discuss disorders of the thyroid-gut axis and identify the evidence base behind the management of such disorders. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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.

Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus.

PubMed

Tüysüz, Beyhan; Collin, Anna; Arapoğlu, Müjde; Suyugül, Nezir

2009-10-01

Waardenburg-Shah syndrome (Waardenburg syndrome type IV-WS4) is an auditory-pigmentary disorder that combines clinical features of pigmentary abnormalities of the skin, hair and irides, sensorineural hearing loss, and Hirschsprung disease (HSCR). Mutations in the endothelin-B receptor (EDNRB) gene on 13q22 have been found to cause this syndrome. Mutations in both alleles cause the full phenotype, while heterozygous mutations cause isolated HSCR or HSCR with minor pigmentary anomalies and/or sensorineural deafness. We investigated the status of the EDNRB gene, by FISH analysis, in three patients with de novo proximal 13q deletions detected at cytogenetic analysis and examined the clinical variability of WS4 among these patients. Chromosome 13q was screened with locus specific FISH probes and breakpoints were determined at 13q22.1q31.3 in Patients 1 and 3, and at 13q21.1q31.3 in Patient 2. An EDNRB specific FISH probe was deleted in all three patients. All patients had common facial features seen in proximal 13q deletion syndrome and mild mental retardation. However, findings related to WS4 were variable; Patient 1 had hypopigmentation of the irides and HSCR, Patient 2 had prominent bicolored irides and mild bilateral hearing loss, and Patient 3 had only mild unilateral hearing loss. These data contribute new insights into the pathogenesis of WS4.

Distribution of clinical phenotypes in patients with chronic obstructive pulmonary disease caused by biomass and tobacco smoke.

PubMed

Golpe, Rafael; Sanjuán López, Pilar; Cano Jiménez, Esteban; Castro Añón, Olalla; Pérez de Llano, Luis A

2014-08-01

Exposure to biomass smoke is a risk factor for chronic obstructive pulmonary disease (COPD). It is unknown whether COPD caused by biomass smoke has different characteristics to COPD caused by tobacco smoke. To determine clinical differences between these two types of the disease. Retrospective observational study of 499 patients with a diagnosis of COPD due to biomass or tobacco smoke. The clinical variables of both groups were compared. There were 122 subjects (24.4%) in the biomass smoke group and 377 (75.5%) in the tobacco smoke group. In the tobacco group, the percentage of males was higher (91.2% vs 41.8%, P<.0001) and the age was lower (70.6 vs 76.2 years, P<.0001). Body mass index and FEV1% values were higher in the biomass group (29.4±5.7 vs 28.0±5.1, P=.01, and 55.6±15.6 vs 47.1±17.1, P<.0001, respectively). The mixed COPD-asthma phenotype was more common in the biomass group (21.3% vs 5%, P<.0001), although this difference disappeared when corrected for gender. The emphysema phenotype was more common in the tobacco group (45.9% vs 31.9%, P=.009). The prevalence of the chronic bronchitis and exacerbator phenotypes, the comorbidity burden and the rate of hospital admissions were the same in both groups. Differences were observed between COPD caused by biomass and COPD caused by tobacco smoke, although these may be attributed in part to uneven gender distribution between the groups. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Low-dose aspirin for prevention of cardiovascular disease in patients on hemodialysis: A 5-y prospective cohort study.

PubMed

Liu, Jun; Pan, Yu; Chen, Lei; Qiao, Qing Yan; Wang, Jing; Pan, Li Hua; Gu, Yan Hong; Gu, Hui Fang; Fu, Shun Kun; Jin, Hui Min

2016-10-01

Introduction Aspirin is an effective antiplatelet drug for preventing cardiovascular events in high-risk subjects. However, for patients with chronic kidney disease and undergoing hemodialysis (HD), its preventive efficacy remains controversial. The present study aimed to determine whether aspirin therapy reduces the risk of cardiovascular disease (CVD) and all-cause mortality in patients on HD. Methods We conducted a 5-y prospective cohort study involving patients on HD. Major exposure variables included prescription of aspirin (100 mg/d) and no aspirin (nonaspirin). The primary outcomes included all-cause death, cardiovascular events, hemorrhage, and ischemic stroke. The secondary outcome included bleeding events defined by the requirement of hospitalization. Findings In this study, 406 patients on regular HD were involved during a 5-y follow-up. Among these, 152 and 254 propensity-matched patients were enrolled in the aspirin and nonaspirin cohort, respectively. The cumulative survival rate was not significantly higher in the aspirin than in the nonaspirin users (log rank χ 2  = 1.080, P = 0.299). Aspirin use was not significantly associated with reduced all-cause mortality, fatal and nonfatal congestive heart failure, as well as acute myocardial infarction and ischemic stroke. The risk of fatal cerebral hemorrhage was not significantly increased in the aspirin users (HR = 1.795, 95% CI 0.666-4.841, P = 0.174). After adjustment for other confounders, aspirin use was also not associated with decreased risk of all-cause mortality and CVD. Discussion The present prospective cohort study suggests that low-dose aspirin use is not associated with a significant decrease in the risks of all-cause mortality, CVD, and stroke in population undergoing HD (ClinicalTrials.gov number, NCT02261025). © 2016 International Society for Hemodialysis.

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.

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.

Neuropathological Comparison of Adult Onset and Juvenile Huntington's Disease with Cerebellar Atrophy: A Report of a Father and Son.

PubMed

Latimer, Caitlin S; Flanagan, Margaret E; Cimino, Patrick J; Jayadev, Suman; Davis, Marie; Hoffer, Zachary S; Montine, Thomas J; Gonzalez-Cuyar, Luis F; Bird, Thomas D; Keene, C Dirk

2017-01-01

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a trinucleotide (CAG) repeat expansion in huntingtin (HTT) on chromosome 4. Anticipation can cause longer repeat expansions in children of HD patients. Juvenile Huntington's disease (JHD), defined as HD arising before age 20, accounts for 5-10% of HD cases, with cases arising in the first decade accounting for approximately 1%. Clinically, JHD differs from the predominately choreiform adult onset Huntington's disease (AOHD) with variable presentations, including symptoms such as myoclonus, seizures, Parkinsonism, and cognitive decline. The neuropathologic changes of AOHD are well characterized, but there are fewer reports that describe the neuropathology of JHD. Here we report a case of a six-year-old boy with paternally-inherited JHD caused by 169 CAG trinucleotide repeats who presented at age four with developmental delay, dysarthria, and seizures before dying at age 6. The boy's clinical presentation and neuropathological findings are directly compared to those of his father, who presented with AOHD and 54 repeats. A full autopsy was performed for the JHD case and a brain-only autopsy was performed for the AOHD case. Histochemically- and immunohistochemically-stained slides were prepared from formalin-fixed, paraffin-embedded tissue sections. Both cases had neuropathology corresponding to Vonsattel grade 3. The boy also had cerebellar atrophy with huntingtin-positive inclusions in the cerebellum, findings not present in the father. Autopsies of father and son provide a unique opportunity to compare and contrast the neuropathologic findings of juvenile and adult onset HD while also providing the first immunohistochemical evidence of cerebellar involvement in JHD. Additionally this is the first known report to include findings from peripheral tissue in a case of JHD.

Vitamin D and public health: an overview of recent research on common diseases and mortality in adulthood.

PubMed

Scragg, Robert

2011-09-01

There is increasing interest in vitamin D and its possible health effects. The aims of the present overview are to summarise the research on common diseases for which there is substantial evidence on vitamin D, identify diseases where vitamin D may be beneficial and discuss the public health implications of these findings. Literature search of PubMed for the years 2000 to 2010 to identify cohort studies with baseline measures of 25-hydroxyvitamin D (25(OH)D) and randomised controlled trials (RCT) of vitamin D supplementation in relation to fractures, colorectal cancer, CVD and all-cause mortality. Risk ratios of disease from comparisons between 25(OH)D quantiles in these studies were summarised using RevMan software version 5·1 (The Nordic Cochrane Centre, Copenhagen). Community-based samples recruited into cohort studies from many countries. Older men and women, mostly above 50 years of age. When comparing the lowest 25(OH)D category with the highest (or reference), the pooled risk ratio (95 % CI) was: 1·34 (1·13, 1·59) for fractures from nine studies; 1·59 (1·30, 1·95) for colorectal cancer from nine studies; 1·35 (1·17, 1·56) for CVD from twelve studies; and 1·42 (1·23, 1·63) for all-cause mortality from twelve studies. Cohort studies show that baseline 25(OH)D levels predict increased risk of fractures, colorectal cancer, CVD and all-cause mortality. These associations are weak and could be explained by confounding variables such as obesity and physical activity. Because of their potential public health significance, RCT using vitamin D doses ≥50 μg/d are required to determine whether vitamin D protects against these diseases.

Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype.

PubMed

Goolsby Hunter, Alyssa; Rosenblatt, Lisa; Patel, Chad; Blauer-Peterson, Cori; Anduze-Faris, Beatrice

2017-05-01

In the United States, approximately 3 million people are infected with hepatitis C virus (HCV). Genotypes of HCV variably affect disease progression and treatment response. However, the relationships between HCV genotypes and liver disease progression, healthcare resource utilization, and healthcare costs have not been fully explored. In this retrospective study of patients with chronic hepatitis C (CHC), healthcare claims from a large US health plan were used to collect data on patient demographic and clinical characteristics. Main outcome measures include healthcare resource utilization (HCRU) and healthcare costs. Linked laboratory data provided genotype and select measures to determine liver disease severity. The sample (mean age 50.6 years, 63.5% male) included 10,331 patients, of whom 79.1% had genotype (GT)1, 12.8% had GT2, and 8.1% had GT3. Descriptive analyses demonstrated variation by HCV genotype in liver and non-liver related comorbidities, liver disease severity, and healthcare costs. The highest percentage of patients with liver-related comorbidities and advanced liver disease was found among those with GT3. Meanwhile, patients with GT2 had lower HCRU and the lowest costs, and patients with GT1 had the highest total all-cause costs. These differences may reflect differing rates of non-liver-related comorbidities and all-cause care. Multivariable analyses showed that genotype was a significant predictor of costs and liver disease severity: compared with patients having GT1, those with GT3 were significantly more likely to have advanced liver disease. Patients with GT2 were significantly less likely to have advanced disease and more likely to have lower all-cause costs. Results may not be generalizable to patients outside the represented commercial insurance plans, and analysis of a prevalent population may underestimate HCRU and costs relative to a sample of treated patients. These results suggest that liver disease progression varies by genotype and that CHC patients with GT3 appear to have more severe liver disease. These findings highlight the importance of effective HCV treatment for all patients and support guidelines for treatment of high-risk patients, including those with GT3.

Spread of Cryptococcus gattii into Pacific Northwest Region of the United States

PubMed Central

Datta, Kausik; Bartlett, Karen H.; Baer, Rebecca; Byrnes, Edmond; Galanis, Eleni; Heitman, Joseph; Hoang, Linda; Leslie, Mira J.; MacDougall, Laura; Magill, Shelley S.; Morshed, Muhammad G.

2009-01-01

Cryptococcus gattii has emerged as a human and animal pathogen in the Pacific Northwest. First recognized on Vancouver Island, British Columbia, Canada, it now involves mainland British Columbia, and Washington and Oregon in the United States. In Canada, the incidence of disease has been one of the highest worldwide. In the United States, lack of cryptococcal species identification and case surveillance limit our knowledge of C. gattii epidemiology. Infections in the Pacific Northwest are caused by multiple genotypes, but the major strain is genetically novel and may have emerged recently in association with unique mating or environmental changes. C. gattii disease affects immunocompromised and immunocompetent persons, causing substantial illness and death. Successful management requires an aggressive medical and surgical approach and consideration of potentially variable antifungal drug susceptibilities. We summarize the study results of a group of investigators and review current knowledge with the goal of increasing awareness and highlighting areas where further knowledge is required. PMID:19757550

Genetic contribution to neurodevelopmental outcomes in congenital heart disease: are some patients predetermined to have developmental delay?

PubMed

Rollins, Caitlin K; Newburger, Jane W; Roberts, Amy E

2017-10-01

Neurodevelopmental impairment is common in children with moderate to severe congenital heart disease (CHD). As children live longer and healthier lives, research has focused on identifying causes of neurodevelopmental morbidity that significantly impact long-term quality of life. This review will address the role of genetic factors in predicting neurodevelopmental outcome in CHD. A robust literature suggests that among children with various forms of CHD, those with known genetic/extracardiac anomalies are at highest risk of neurodevelopmental impairment. Advances in genetic technology have identified genetic causes of CHD in an increasing percentage of patients. Further, emerging data suggest substantial overlap between mutations in children with CHD and those that have previously been associated with neurodevelopmental disorders. Innate and patient factors appear to be more important in predicting neurodevelopmental outcome than medical/surgical variables. Future research is needed to establish a broader understanding of the mutations that contribute to neurodevelopmental disorders and the variations in expressivity and penetrance.

Diet and coronary heart disease in England and Wales during and after the second world war.

PubMed

Barker, D J; Osmond, C

1986-03-01

During the second world war there were large changes in consumption of fats, fibre, and sugar in Britain. These changes matched recent recommendations made by the Committee on Medical Aspects of Food Policy (COMA) with the object of reducing the incidence of coronary heart disease (CHD). It is widely believed that CHD mortality fell during the war. This paper re-examines CHD mortality among middle-aged people in England and Wales from 1931 to 1967. After allowance for changes in the rules for coding cause of death, and for the sharp increase in all-causes mortality in 1940, there is little to suggest that time trends in CHD were much influenced by the war. Because of confounding variables, this does not argue against the COMA report. However, it gives no support to the view that compliance with the recommendations on fat, fibre, and sugar will lead, by itself, to an appreciable fall in CHD mortality in middle-aged people.

Vaccination against bacterial kidney disease: Chapter 22

USGS Publications Warehouse

Elliott, Diane G.; Wiens, Gregory D.; Hammell, K. Larry; Rhodes, Linda D.; Edited by Gudding, Roar; Lillehaug, Atle; Evensen, Øystein

2014-01-01

Bacterial kidney disease (BKD) of salmonid fishes, caused by Renibacterium salmoninarum, has been recognized as a serious disease in salmonid fishes since the 1930s. This chapter discusses the occurrence and significance, etiology, and pathogenesis of BKD. It then describes the different vaccination procedures and the effects and side-effects of vaccination. Despite years of research, however, only a single vaccine has been licensed for prevention of BKD, and has demonstrated variable efficacy. Therefore, in addition to a presentation of the current status of BKD vaccination, a discussion of potential future directions for BKD vaccine development is included in the chapter. This discussion is focused on the unique characteristics of R. salmoninarum and its biology, as well as aspects of the salmonid immune system that might be explored specifically to develop more effective vaccines for BKD prevention.

Respiratory health issues in the Asia-Pacific region: an overview.

PubMed

Jamrozik, Euzebiusz; Musk, Arthur William

2011-01-01

The Asia-Pacific region is home to a large heterogeneous population whose respiratory health is influenced by diverse social, economic and environmental factors. Despite this variability, the most prevalent causes of respiratory morbidity and mortality are tobacco smoking, infection, and air pollution. This review aims to summarize current respiratory health issues in the region including smoking-related diseases especially COPD, lung cancer and infectious problems such as pandemic influenza, the severe acute respiratory syndrome coronavirus, bacterial pneumonia and tuberculosis, as well as the contribution of air pollution to respiratory disease. Published data on trends in the epidemiology and management of respiratory diseases and are summarized; finally, the limitations of available data and projections for the future of respiratory health in the region are discussed. © 2010 Commonwealth of Australia. Respirology © 2010 Asian Pacific Society of Respirology.

Programming of cardiovascular disease across the life-course.

PubMed

Blackmore, Heather L; Ozanne, Susan E

2015-06-01

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality, affecting both developed and developing countries. Whilst it is well recognized that our risk of CVD can be determined by the interaction between our genetics and lifestyle, this only partly explains the variability at the population level. Based on these well-known risk factors, for many years, intervention and primary prevention strategies have focused on modifying lifestyle factors in adulthood. However, research shows that our risk of CVD can be pre-determined by our early life environment and this area of research is known as the Developmental Origins of Health and Disease. The aim of this review is to evaluate our current understanding of mechanisms underlying the programming of CVD. This article is part of a special issue entitled CV Aging. Copyright © 2014 Elsevier Ltd. All rights reserved.

LEPROSY NEPHROPATHY: A REVIEW OF CLINICAL AND HISTOPATHOLOGICAL FEATURES

PubMed Central

da Silva, Geraldo Bezerra; Daher, Elizabeth De Francesco; Pires, Roberto da Justa; Pereira, Eanes Delgado Barros; Meneses, Gdayllon Cavalcante; Araújo, Sônia Maria Holanda Almeida; Barros, Elvino José Guardão

2015-01-01

Leprosy is a chronic disease caused by Mycobacterium leprae, highly incapacitating, and with systemic involvement in some cases. Renal involvement has been reported in all forms of the disease, and it is more frequent in multibacillary forms. The clinical presentation is variable and is determined by the host immunologic system reaction to the bacilli. During the course of the disease there are the so called reactional states, in which the immune system reacts against the bacilli, exacerbating the clinical manifestations. Different renal lesions have been described in leprosy, including acute and chronic glomerulonephritis, interstitial nephritis, secondary amyloidosis and pyelonephritis. The exact mechanism that leads to glomerulonephritis in leprosy is not completely understood. Leprosy treatment includes rifampicin, dapsone and clofazimine. Prednisone and non-steroidal anti-inflammatory drugs may be used to control acute immunological episodes. PMID:25651321

Cardiovascular risk in Turner syndrome.

PubMed

Donato, Beatriz; Ferreira, Maria João

2018-06-01

Turner syndrome is a relatively common genetic disorder of female development, characterized by partial or complete absence of an X chromosome, with a variable clinical presentation. Congenital or acquired cardiovascular disease is highly prevalent and a major cause of early death in this syndrome. The most feared complication is aortic dissection, which can occur at a very young age and requires careful assessment of its risk factors. A systematic literature search identified sixty relevant publications. These were reviewed with regard to the increased risk of cardiovascular disease in women with Turner syndrome, especially in pregnancy. The most common congenital cardiovascular defects are presented and illustrated with appropriate iconography. The current recommendations regarding the screening and monitoring of cardiovascular disease in these patients are discussed. Copyright © 2018 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

[Impact of antiviral therapy on the natural history of hepatitis C virus].

PubMed

Fernández Rodriguez, Conrado M; Gutierrez Garcia, Maria Luisa

2014-12-01

Chronic hepatitis C virus infection affects around 150 million persons, and 350,000 persons worldwide die of this disease each year. Although the data on its natural history are incomplete, after the acute infection, most patients develop chronic forms of hepatitis C with variable stages of fibrosis. In these patients, continual inflammatory activity can cause significant fibrosis, cirrhosis, decompensation of the liver disease, or hepatocarcinoma. In the next few years, it is expected that hepatitis C virus infection and its complications will significantly increase, as will the incidence of hepatocarcinoma in Spain. This review presents the data on the natural history of hepatitis C virus infection and discusses the potential impact of antiviral therapy on the distinct stages of the disease. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Characterization of Eyeball Loss in Four Cities of Colombia.

PubMed

Moreno-Caviedes, F Hernán; Velez Cuellar, Nórida; Caicedo Zapata, Margarita; Triana Reina, Gabriel; Sánchez, Azucena

2017-09-11

Describe the socio-demographic characteristics of anophthalmic patients examined at specialized centers of four cities in Colombia to know the different causes of eyeball loss. A transversal retrospective study was done of 511 medical records from the specialized practices of four cities in Colombia. Socio-demographic data of patients who were seen between January 2011 and December 2013 were compiled. SOFA Statistics software v1.4.6 was used for this analysis. An analysis throughout the measures of central tendency for numerical variables was developed, and the descriptive statistics were used for the categorical variables. Almost 63% of the data belonged to male patients. Eyeball loss was more frequent in patients over 40 years of age. Fifty-one percent of the patients suffered eyeball loss due to traumatic causes, 40.2% due to pathological causes, and 4.6% due to congenital anomalies. The most frequent specific causes were glaucoma (19%), ocular cancer (15.4%), and home accidents (11,2%). Around 60% of the anophthalmic patients belonged to low socioeconomic level. It is important to highlight that more than half of the analyzed anophthalmia cases originated in some type of trauma; this means that they could be considered potentially avoidable losses. Complications deriving from glaucoma became the most frequent cause of anophthalmia in the pathological origin group, which suggests a reflection regarding the strategies of early detection of the disease and access to proper treatment. It is also showed the need to develop an efficient system to manage information.

Health-related variables and predictors of Health-promoting Lifestyle in cardiovascular disease patients.

PubMed

Mohsenipouya, Hossein; Majlessi, Fereshteh; Shojaeizadeh, Davood; Foroushani, Abbas Rahimi; Ghafari, Rahman; Habibi, Vali; Makrani, Azam Seyfi

2016-04-01

The principal cause for death in the world is cardiovascular disease. Poor lifestyle is a contributing element in this regard. The objective of this study was to estimate the effects of health-related variables and lifestyle variables on the results of exercise stress tests in patients with cardiovascular disease in Iran. The study population in this case-control study was 220 patients who were candidates for exercise stress tests in Mazandaran Province (Iran) in 2015. The patients were divided randomly into two groups based on the results of their exercise stress tests, i.e., positive (110 patients) and negative (110 patients). The data collection tool was a standard questionnaire entitled "Health promotion lifestyle profile-II." The data were analyzed using mean, standard deviation, the chi-squared test, and logistic regression by SPSS version 22 software. The risk of a positive exercise stress test increases with age. The age group above 65 was 1.049 times more at risk of a positive exercise stress test than the age group of less than 45. The people with dyslipidemia had 1.635 times greater risk of positive exercise stress tests than the group without dyslipidemia. In addition, patients with hypertension had 1.579 times greater risk of positive exercise stress tests than the group without hypertension. The lack of individual health responsibility (Odds ratio (OR): 1.622), stress management (OR: 1.592), and physical activity (OR: 1.245) contributed more to positive exercise tests than the other risk factors. Educational interventions can improve the responsibility for health, physical activity, and stress management among people with the risk of cardiovascular disease.

Recurrent Rearrangements of Chromosome 1q21.1 and Variable Pediatric Phenotypes

PubMed Central

Mefford, Heather C.; Sharp, Andrew J.; Baker, Carl; Itsara, Andy; Jiang, Zhaoshi; Buysse, Karen; Huang, Shuwen; Maloney, Viv K.; Crolla, John A.; Baralle, Diana; Collins, Amanda; Mercer, Catherine; Norga, Koen; de Ravel, Thomy; Devriendt, Koen; Bongers, Ernie M.H.F.; de Leeuw, Nicole; Reardon, William; Gimelli, Stefania; Bena, Frederique; Hennekam, Raoul C.; Male, Alison; Gaunt, Lorraine; Clayton-Smith, Jill; Simonic, Ingrid; Park, Soo Mi; Mehta, Sarju G.; Nik-Zainal, Serena; Woods, C. Geoffrey; Firth, Helen V.; Parkin, Georgina; Fichera, Marco; Reitano, Santina; Giudice, Mariangela Lo; Li, Kelly E.; Casuga, Iris; Broomer, Adam; Conrad, Bernard; Schwerzmann, Markus; Räber, Lorenz; Gallati, Sabina; Striano, Pasquale; Coppola, Antonietta; Tolmie, John L.; Tobias, Edward S.; Lilley, Chris; Armengol, Lluis; Spysschaert, Yves; Verloo, Patrick; De Coene, Anja; Goossens, Linde; Mortier, Geert; Speleman, Frank; van Binsbergen, Ellen; Nelen, Marcel R.; Hochstenbach, Ron; Poot, Martin; Gallagher, Louise; Gill, Michael; McClellan, Jon; King, Mary-Claire; Regan, Regina; Skinner, Cindy; Stevenson, Roger E.; Antonarakis, Stylianos E.; Chen, Caifu; Estivill, Xavier; Menten, Björn; Gimelli, Giorgio; Gribble, Susan; Schwartz, Stuart; Sutcliffe, James S.; Walsh, Tom; Knight, Samantha J.L.; Sebat, Jonathan; Romano, Corrado; Schwartz, Charles E.; Veltman, Joris A.; de Vries, Bert B.A.; Vermeesch, Joris R.; Barber, John C.K.; Willatt, Lionel; Tassabehji, May; Eichler, Evan E.

2009-01-01

BACKGROUND Duplications and deletions in the human genome can cause disease or predispose persons to disease. Advances in technologies to detect these changes allow for the routine identification of submicroscopic imbalances in large numbers of patients. METHODS We tested for the presence of microdeletions and microduplications at a specific region of chromosome 1q21.1 in two groups of patients with unexplained mental retardation, autism, or congenital anomalies and in unaffected persons. RESULTS We identified 25 persons with a recurrent 1.35-Mb deletion within 1q21.1 from screening 5218 patients. The microdeletions had arisen de novo in eight patients, were inherited from a mildly affected parent in three patients, were inherited from an apparently unaffected parent in six patients, and were of unknown inheritance in eight patients. The deletion was absent in a series of 4737 control persons (P = 1.1×10−7). We found considerable variability in the level of phenotypic expression of the microdeletion; phenotypes included mild-to-moderate mental retardation, microcephaly, cardiac abnormalities, and cataracts. The reciprocal duplication was enriched in the nine children with mental retardation or autism spectrum disorder and other variable features (P = 0.02). We identified three deletions and three duplications of the 1q21.1 region in an independent sample of 788 patients with mental retardation and congenital anomalies. CONCLUSIONS We have identified recurrent molecular lesions that elude syndromic classification and whose disease manifestations must be considered in a broader context of development as opposed to being assigned to a specific disease. Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype. PMID:18784092

Exclusion of the APC gene as the cause of a variant form of familial adenomatous polyposis (FAP)

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

Stella, A.; Resta, N.; Susca, F.

Familial adenomatous polyposis (FAP) is a premalignant disease inherited as an autosomal dominant trait, characterized by hundreds to thousands of polyps in the colorectal tract. Recently, the syndrome has been shown to be caused by mutations in the APC (adenomatous polyposis coli) gene located on chromosome 5q21. The authors studied two families that both presented a phenotype different from that of the classical form of FAP. The most important findings observed in these two kindreds are (a) low and variable number of colonic polyps (from 5 to 100) and (b) a slower evolution of the disease, with colon cancer occurringmore » at a more advanced age than in FAP in spite of the early onset of intestinal manifestations. To determine whether mutations of the APC gene are also responsible for this variant syndrome, linkage studies were performed by using a series of markers both intragenic and tightly linked to the APC gene. The results provide evidence for exclusion of the APC gene as the cause of the variant form of polyposis present in the two families described. 30 refs., 1 fig., 1 tab.« less

Illness beliefs and psychological outcome in people with Parkinson's disease.

PubMed

Simpson, Jane; Lekwuwa, Godwin; Crawford, Trevor

2013-06-01

Illness beliefs are important predictors of psychological outcome in people with chronic illness and evidence suggests these could also be significant in furthering our understanding of psychological functioning in people with Parkinson's disease. Illness beliefs are specific, dynamic representations of an illness and cover dimensions such as cause, identity, consequences and controllability. Eighty-one people with Parkinson's disease completed a series of questionnaires to provide demographic, clinical and psychosocial data, which were then used to assess the relative impact of illness beliefs on their psychological functioning. Psychological functioning was assessed by measuring levels of depression, anxiety, stress, positive affect and emotional well-being. Hierarchical block regression indicated that illness beliefs were important independent predictors across some but not all outcomes and the results emphasised the importance of testing new predictors against more established predictors of outcome such as physical functioning and self-esteem. The illness beliefs most important in psychological outcome in people with PD were causal beliefs (particularly in psychosocial causes) and illness coherence (the level of understanding of the illness). The therapeutic potential of psychosocial variables was discussed given that these can be modified during therapy and this change can positively influence psychological outcome.

Exploring molecular variation in Schistosoma japonicum in China.

PubMed

Young, Neil D; Chan, Kok-Gan; Korhonen, Pasi K; Min Chong, Teik; Ee, Robson; Mohandas, Namitha; Koehler, Anson V; Lim, Yan-Lue; Hofmann, Andreas; Jex, Aaron R; Qian, Baozhen; Chilton, Neil B; Gobert, Geoffrey N; McManus, Donald P; Tan, Patrick; Webster, Bonnie L; Rollinson, David; Gasser, Robin B

2015-12-01

Schistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets, and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.

Velocardiofacial syndrome in Mexican patients: Unusually high prevalence of congenital heart disease.

PubMed

Márquez-Ávila, Candy Sue; Vizcaíno-Alarcón, Alfredo; García-Delgado, Constanza; Núñez-Martínez, Paulina María; Flores-Ramírez, Francisco; Reyes-de la Rosa, Alejandra del Pilar; Mendelsberg-Fishbein, Paola; Ibarra-Grajeda, Diana; Medina-Bravo, Patricia; Balderrábano-Saucedo, Norma; Esteva-Solsona, Salvador; Márquez-Quiróz, Luz del Carmen; Flores-Cuevas, Arturo; Sánchez-Urbina, Rocío; Morales-Jiménez, Ariadna Berenice; Garibay-Nieto, Nayely; Del Bosque-Garza, Jesús; Pietropaolo-Cienfuegos, Dino; Gutiérrez-Camacho, Claudia; García-Morales, Leticia; Morán-Barroso, Verónica Fabiola

2015-11-01

Velocardiofacial syndrome (VCFS) is the most common microdeletion syndrome with an incidence of 1:4000 live births. Its phenotype is highly variable with facial, velopharyngeal, cardiac, endocrine, immunologic and psychiatric abnormalities. It is caused by a microdeletion in chromosome 22q11.2. We present 7 years of experience evaluating patients with VCFS regarding their main clinical characteristics. The patients included were multidisciplinary evaluated and had a positive FISH analysis for del22q11.2. A total of 62 patients were assessed, a 34 female/28 male ratio was observed with ages ranging from 9 days to 16 years, all but one patient had typical facial features. A diagnosis of congenital heart disease was established in 97% of the patients; other clinical characteristics were identified with different percentages such as cleft palate, and hypocalcaemia. Three cases had a familial presentation. While the clinical findings of this study were in general terms in keeping with the literature, it is interesting the unexpectedly high percentage of congenital heart disease identified in Mexican children with VCFS that also was the main cause for clinical referral. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pharmacogenetic biomarkers of response in Crohn's disease.

PubMed

Linares-Pineda, T M; Cañadas-Garre, M; Sánchez-Pozo, A; Calleja-Hernández, M Á

2018-01-01

Crohn's disease (CD) is a chronic condition, which affects the immune system. It can also affect any part of the digestive tract and be associated with external manifestations. The causes of the disease remain unknown, although it seems to be the result of a combination of factors, such as genetic predisposition, environment, lifestyle and the composition of the microbiota, among others. The treatment protocol begins with a change in eating and smoking habits, and is continued with different lines of treatment, including corticosteroids, immunomodulators and biologic therapy (infliximab and adalimumab), which have shown differences in response among patients, especially with biologic treatment. Several studies have considered the possibility that these differences in response are caused by the genetic variability of patients. Many genes have been investigated as potential predictors of response to biological drugs, such as ADAM17, ATG16L1, EMSY, CASP9, CCNY, CNTN5, FASLG, FCGR, NOD2, PTGER4, IL13, IL1B, IL27, IL11, IL17F, TNF and TNFR genes. In this review, we will gather the information on influence of gene polymorphisms investigated to date on response to biological drugs in CD patients.

Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure

PubMed Central

Rengo, Giuseppe; Pagano, Gennaro; Filardi, Pasquale Perrone; Femminella, Grazia Daniela; Parisi, Valentina; Cannavo, Alessandro; Liccardo, Daniela; Komici, Klara; Gambino, Giuseppina; D’Amico, Maria Loreta; de Lucia, Claudio; Paolillo, Stefania; Trimarco, Bruno; Vitale, Dino Franco; Ferrara, Nicola; Koch, Walter J; Leosco, Dario

2016-01-01

Rationale Sympathetic nervous system (SNS) hyperactivity is associated with poor prognosis in patients with HF, yet routine assessment of SNS activation is not recommended for clinical practice. Myocardial G protein-coupled receptor kinase 2 (GRK2) is up-regulated in heart failure (HF) patients, causing dysfunctional β-adrenergic receptor signaling. Importantly, myocardial GRK2 levels correlate with levels found in peripheral lymphocytes of HF patients. Objective The independent prognostic value of blood GRK2 measurements in HF patients has never been investigated, thus, the purpose of the present study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients. Methods and Results We prospectively studied 257 HF patients with mean left ventricular ejection fraction (LVEF) of 31.4±8.5%. At the time of enrollment, plasma norepinephrine, serum NT-proBNP and lymphocyte GRK2 levels, as well as clinical and instrumental variables were measured. The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause mortality was assessed using the Cox proportional hazard model including demographic, clinical, instrumental and laboratory data. Over a mean follow-up period of 37.5±20.2 months (range: 3–60 months) there were 102 CV deaths. Age, LVEF, NYHA class, Chronic Obstructive Pulmonary Disease, Chronic Kidney Disease, N-terminal-pro Brain Natriuretic Peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mortality in HF patients. GRK2 levels showed an additional prognostic and clinical value over demographic and clinical variables. The independent prognostic value of lymphocyte GRK2 levels was also confirmed for all-cause mortality. Conclusion Lymphocyte GRK2 protein levels can independently predict prognosis in patients with HF. PMID:26884616

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.

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber’s hereditary optic neuropathy

PubMed Central

Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N.; D’Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F.; Zeviani, Massimo; Salomao, Solange R.; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A.; Tancredi, Andrea; Mancini, Massimiliano; d’Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro

2014-01-01

Leber’s hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber’s hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber’s hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies. PMID:24369379

Relationship Between Chronic Obstructive Pulmonary Disease and Air Pollutants Depending on the Origin and Trajectory of Air Masses in the North of Spain.

PubMed

Santurtún, Ana; Rasilla, Domingo F; Riancho, Leyre; Zarrabeitia, María T

2017-11-01

Chronic obstructive pulmonary disease (COPD) is a common respiratory condition and one of the leading causes of death. Our aim was to analyze the association between emergency room visits due to this disease and meteorological variables and atmospheric contaminant levels in Santander, depending on the origin and trajectory of air masses. Data from emergency room visits at Hospital Marqués de Valdecilla were collected on a daily basis during an 8-year period. Data on concentrations of the main atmospheric pollutants and meteorological variables were also recorded.Retrotrajectories leading to Santander at a height of1,500 meters above sea level were then calculated. Finally, a correlation model was produced to evaluate the effect of the contaminants on emergency visitsdue to COPD. There is a direct association between PM 10 levels and the number of visits to the emergency room due to COPD. For every 10μg/m3 increase in pollutantlevels, emergency visitsincrease by3.34% (p=0.00005), and thiseffect is enhanced in individualsover 74 years of age. This effect is heightened when PM10 levels depend on air masses from the South and when air recirculation occurs. There is no association betweenother pollutants and the number of visits to the emergency room. Exposure to high levels of PM10 causes exacerbations in COPD patients. By studying the atmospheric circulation pattern, we can predict whether PM10 levels will be inappropriately high, and we can also obtain information about the particle components. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Heart rate variability is a predictor of mortality in chronic kidney disease: a report from the CRIC Study.

PubMed

Drawz, Paul E; Babineau, Denise C; Brecklin, Carolyn; He, Jiang; Kallem, Radhakrishna R; Soliman, Elsayed Z; Xie, Dawei; Appleby, Dina; Anderson, Amanda H; Rahman, Mahboob

2013-01-01

Low heart rate variability (HRV) is a risk factor for adverse outcomes in the general population. We aimed to determine the factors associated with HRV and evaluate the association between low HRV and clinical outcomes in patients with chronic kidney disease (CKD). A 10-second electrocardiogram was obtained at baseline in the Chronic Renal Insufficiency Cohort (CRIC) Study. HRV was measured by the standard deviation of all R-R intervals (SDNN) and the root mean square of successive differences between R-R intervals (RMSSD). In 3,245 CRIC participants with available baseline SDNN and RMSSD, lower HRV was associated with older age, lack of exercise, heart failure, elevated phosphorus and hemoglobin A1c, and low estimated glomerular filtration rate. After a median follow-up of 4.2 years, in fully adjusted models, lower HRV was not associated with renal [SDNN: hazard rate, HR = 0.96 (95% confidence interval, CI 0.88-1.05); RMSSD: HR = 0.97 (95% CI 0.88-1.07)] or cardiovascular outcomes [SDNN: HR = 1.02 (95% CI 0.92-1.13); RMSSD: HR = 1.00 (95% CI 0.90-1.10)]. There was a nonlinear relationship between RMSSD and all-cause mortality with increased risk with both low and high RMSSD (p = 0.04). In a large cohort of patients with CKD, multiple risk factors for renal and cardiovascular diseases were associated with lower HRV. Lower HRV was not associated with increased risk for renal or cardiovascular outcomes, but both low and high RMSSD were associated with increased risk for all-cause mortality. In conclusion, HRV measured by RMSSD may be a novel and independent risk factor for mortality in CKD patients. © 2013 S. Karger AG, Basel.

Waardenburg syndrome type 4: report of two new cases caused by SOX10 mutations in Spain.

PubMed

Fernández, Raquel M; Núñez-Ramos, Raquel; Enguix-Riego, M Valle; Román-Rodríguez, Francisco José; Galán-Gómez, Enrique; Blesa-Sánchez, Emilio; Antiñolo, Guillermo; Núñez-Núñez, Ramón; Borrego, Salud

2014-02-01

Shah-Waardenburg syndrome or Waardenburg syndrome type 4 (WS4) is a neurocristopathy characterized by the association of deafness, depigmentation and Hirschsprung disease. Three disease-causing genes have been identified so far for WS4: EDNRB, EDN3, and SOX10. SOX10 mutations, found in 45-55% of WS4 patients, are inherited in autosomal dominant way. In addition, mutations in SOX10 are also responsible for an extended syndrome involving peripheral and central neurological phenotypes, referred to as PCWH (peripheral demyelinating neuropathy, central dysmyelinating leucodystrophy, Waardenburg syndrome, Hirschsprung disease). Such mutations are mostly private, and a high intra- and inter-familial variability exists. In this report, we present a patient with WS4 and a second with PCWH due to SOX10 mutations supporting again the genetic and phenotypic heterogeneity of these syndromes. Interestingly, the WS4 family carries an insertion of 19 nucleotides in exon 5 of SOX10, which results in distinct phenotypes along three different generations: hypopigmentation in the maternal grandmother, hearing loss in the mother, and WS4 in the proband. Since mosaicism cannot explain the three different related-WS features observed in this family, we propose as the most plausible explanation the existence of additional molecular events, acting in an additive or multiplicative fashion, in genes or regulatory regions unidentified so far. On the other hand, the PCWH case was due to a de novo deletion in exon 5 of the gene. Efforts should be devoted to unravel the mechanisms underlying the intrafamilial phenotypic variability observed in the families affected, and to identify new genes responsible for the still unsolved WS4 cases. © 2013 Wiley Periodicals, Inc.

Linkages of Weather and Climate With Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae), Enzootic Transmission of Borrelia burgdorferi, and Lyme Disease in North America

PubMed Central

Eisen, Rebecca J.; Eisen, Lars; Ogden, Nicholas H.; Beard, Charles B.

2016-01-01

Lyme disease has increased both in incidence and geographic extent in the United States and Canada over the past two decades. One of the underlying causes is changes during the same time period in the distribution and abundance of the primary vectors: Ixodes scapularis Say and Ixodes pacificus Cooley and Kohls in eastern and western North America, respectively. Aside from short periods of time when they are feeding on hosts, these ticks exist in the environment where temperature and relative humidity directly affect their development, survival, and host-seeking behavior. Other important factors that strongly influence tick abundance as well as the proportion of ticks infected with the Lyme disease spirochete, Borrelia burgdorferi, include the abundance of hosts for the ticks and the capacity of tick hosts to serve as B. burgdorferi reservoirs. Here, we explore the linkages between climate variation and: 1) duration of the seasonal period and the timing of peak activity; 2) geographic tick distributions and local abundance; 3) enzootic B. burgdorferi transmission cycles; and 4) Lyme disease cases. We conclude that meteorological variables are most influential in determining host-seeking phenology and development, but, while remaining important cofactors, additional variables become critical when exploring geographic distribution and local abundance of ticks, enzootic transmission of B. burgdorferi, and Lyme disease case occurrence. Finally, we review climate change-driven projections for future impact on vector ticks and Lyme disease and discuss knowledge gaps and research needs. PMID:26681789

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.

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

PubMed

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

2016-05-01

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. Published by Oxford University Press on behalf of Entomological Society of America 2016. This work is written by US Government employees and is in the public domain in the US.

Viral load of patients with hantavirus pulmonary syndrome in Argentina.

PubMed

Bellomo, Carla María; Pires-Marczeski, Fanny Clara; Padula, Paula Julieta

2015-11-01

Hantavirus causes severe illness including pneumonia, which leads to hospitalization and often death. At present, there is no specific treatment available. The hantavirus pathogenesis is not well understood, but most likely both virus-mediated and host-mediated mechanisms, are involved. The aim of this study was to correlate viral load in samples of hantavirus pulmonary syndrome cases and hantavirus infected individuals, with clinical epidemiological parameters and disease outcome. The variables that could potentially be related with viral load were analyzed. The retrospective study included 73 cases or household contacts, with different clinical evolution. Viral load was measured by reverse-transcription and real time polymerase chain reaction. There was no statistically significant association between blood viral RNA levels and severity of disease. However, viral load was inversely correlated with IgG response in a statistically significant manner. The level of viral RNA was significantly higher in patients infected with Andes virus South lineage, and was markedly low in persons infected with Laguna Negra virus. These results suggest that the infecting viral genotype is associated with disease severity, and that high viral load is associated with a low specific IgG response. Sex, age and disease severity were not related with viral load. Further investigations increasing strikingly the number of cases and also limiting the variables to be studied are necessary. © 2015 Wiley Periodicals, Inc.

A global map of suitability for coastal Vibrio cholerae under current and future climate conditions.

PubMed

Escobar, Luis E; Ryan, Sadie J; Stewart-Ibarra, Anna M; Finkelstein, Julia L; King, Christine A; Qiao, Huijie; Polhemus, Mark E

2015-09-01

Vibrio cholerae is a globally distributed water-borne pathogen that causes severe diarrheal disease and mortality, with current outbreaks as part of the seventh pandemic. Further understanding of the role of environmental factors in potential pathogen distribution and corresponding V. cholerae disease transmission over time and space is urgently needed to target surveillance of cholera and other climate and water-sensitive diseases. We used an ecological niche model (ENM) to identify environmental variables associated with V. cholerae presence in marine environments, to project a global model of V. cholerae distribution in ocean waters under current and future climate scenarios. We generated an ENM using published reports of V. cholerae in seawater and freely available remotely sensed imagery. Models indicated that factors associated with V. cholerae presence included chlorophyll-a, pH, and sea surface temperature (SST), with chlorophyll-a demonstrating the greatest explanatory power from variables selected for model calibration. We identified specific geographic areas for potential V. cholerae distribution. Coastal Bangladesh, where cholera is endemic, was found to be environmentally similar to coastal areas in Latin America. In a conservative climate change scenario, we observed a predicted increase in areas with environmental conditions suitable for V. cholerae. Findings highlight the potential for vulnerability maps to inform cholera surveillance, early warning systems, and disease prevention and control. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

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.

Ex Vivo Application of Secreted Metabolites Produced by Soil-Inhabiting Bacillus spp. Efficiently Controls Foliar Diseases Caused by Alternaria spp.

PubMed Central

El-Sayed, Ashraf S. A.; Patel, Jaimin S.; Green, Kari B.; Ali, Mohammad; Brennan, Mary; Norman, David

2015-01-01

Bacterial biological control agents (BCAs) are largely used as live products to control plant pathogens. However, due to variable environmental and ecological factors, live BCAs usually fail to produce desirable results against foliar pathogens. In this study, we investigated the potential of cell-free culture filtrates of 12 different bacterial BCAs isolated from flower beds for controlling foliar diseases caused by Alternaria spp. In vitro studies showed that culture filtrates from two isolates belonging to Bacillus subtilis and Bacillus amyloliquefaciens displayed strong efficacy and potencies against Alternaria spp. The antimicrobial activity of the culture filtrate of these two biological control agents was effective over a wider range of pH (3.0 to 9.0) and was not affected by autoclaving or proteolysis. Comparative liquid chromatography-mass spectrometry (LC-MS) analyses showed that a complex mixture of cyclic lipopeptides, primarily of the fengycin A and fengycin B families, was significantly higher in these two BCAs than inactive Bacillus spp. Interaction studies with mixtures of culture filtrates of these two species revealed additive activity, suggesting that they produce similar products, which was confirmed by LC-tandem MS analyses. In in planta pre- and postinoculation trials, foliar application of culture filtrates of B. subtilis reduced lesion sizes and lesion frequencies caused by Alternaria alternata by 68 to 81%. Taken together, our studies suggest that instead of live bacteria, culture filtrates of B. subtilis and B. amyloliquefaciens can be applied either individually or in combination for controlling foliar diseases caused by Alternaria species. PMID:26519395

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.

Temporal variation in temperature determines disease spread and maintenance in Paramecium microcosm populations

PubMed Central

Duncan, Alison B.; Fellous, Simon; Kaltz, Oliver

2011-01-01

The environment is rarely constant and organisms are exposed to temporal and spatial variations that impact their life histories and inter-species interactions. It is important to understand how such variations affect epidemiological dynamics in host–parasite systems. We explored effects of temporal variation in temperature on experimental microcosm populations of the ciliate Paramecium caudatum and its bacterial parasite Holospora undulata. Infected and uninfected populations of two P. caudatum genotypes were created and four constant temperature treatments (26°C, 28°C, 30°C and 32°C) compared with four variable treatments with the same mean temperatures. Variable temperature treatments were achieved by alternating populations between permissive (23°C) and restrictive (35°C) conditions daily over 30 days. Variable conditions and high temperatures caused greater declines in Paramecium populations, greater fluctuations in population size and higher incidence of extinction. The additional effect of parasite infection was additive and enhanced the negative effects of the variable environment and higher temperatures by up to 50 per cent. The variable environment and high temperatures also caused a decrease in parasite prevalence (up to 40%) and an increase in extinction (absence of detection) (up to 30%). The host genotypes responded similarly to the different environmental stresses and their effect on parasite traits were generally in the same direction. This work provides, to our knowledge, the first experimental demonstration that epidemiological dynamics are influenced by environmental variation. We also emphasize the need to consider environmental variance, as well as means, when trying to understand, or predict population dynamics or range. PMID:21450730

Worthy of their name: how floods drive outbreaks of two major floodwater mosquitoes (Diptera: Culicidae).

PubMed

Berec, Ludĕk; Gelbic, Ivan; Sebesta, Oldrich

2014-01-01

An understanding of how climate variables drive seasonal dynamics of mosquito populations is critical to mitigating negative impacts of potential outbreaks, including both nuisance effects and risk of mosquito-borne infectious disease. Here, we identify climate variables most affecting seasonal dynamics of two major floodwater mosquitoes, Aedes vexans (Meigen, 1830) and Aedes sticticus (Meigen, 1838) (Diptera: Culicidae), along the lower courses of the Dyje River, at the border between the Czech Republic and Austria. Monthly trap counts of both floodwater mosquitoes varied both across sites and years. Despite this variability, both models used to fit the observed data at all sites (and especially that for Ae. sticticus) and site-specific models fitted the observed data quite well. The most important climate variables we identified-temperature and especially flooding-were driving seasonal dynamics of both Aedes species. We suggest that flooding determines seasonal peaks in the monthly mosquito trap counts while temperature modulates seasonality in these counts. Hence, floodwater mosquitoes indeed appear worthy of their name. Moreover, the climate variables we considered for modeling were able reasonably to predict mosquito trap counts in the month ahead. Our study can help in planning flood management; timely notification of people, given that these mosquitoes are a real nuisance in this region; public health policy management to mitigate risk from such mosquito-borne diseases as that caused in humans by the Tahyna virus; and anticipating negative consequences of climate change, which are expected only to worsen unless floods, or the mosquitoes themselves, are satisfactorily managed.

Climate variability and change in the United States: potential impacts on water- and foodborne diseases caused by microbiologic agents.

PubMed Central

Rose, J B; Epstein, P R; Lipp, E K; Sherman, B H; Bernard, S M; Patz, J A

2001-01-01

Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments. PMID:11359688

Climate variability and change in the United States: potential impacts on water- and foodborne diseases caused by microbiologic agents.

PubMed

Rose, J B; Epstein, P R; Lipp, E K; Sherman, B H; Bernard, S M; Patz, J A

2001-05-01

Exposure to waterborne and foodborne pathogens can occur via drinking water (associated with fecal contamination), seafood (due to natural microbial hazards, toxins, or wastewater disposal) or fresh produce (irrigated or processed with contaminated water). Weather influences the transport and dissemination of these microbial agents via rainfall and runoff and the survival and/or growth through such factors as temperature. Federal and state laws and regulatory programs protect much of the U.S. population from waterborne disease; however, if climate variability increases, current and future deficiencies in areas such as watershed protection, infrastructure, and storm drainage systems will probably increase the risk of contamination events. Knowledge about transport processes and the fate of microbial pollutants associated with rainfall and snowmelt is key to predicting risks from a change in weather variability. Although recent studies identified links between climate variability and occurrence of microbial agents in water, the relationships need further quantification in the context of other stresses. In the marine environment as well, there are few studies that adequately address the potential health effects of climate variability in combination with other stresses such as overfishing, introduced species, and rise in sea level. Advances in monitoring are necessary to enhance early-warning and prevention capabilities. Application of existing technologies, such as molecular fingerprinting to track contaminant sources or satellite remote sensing to detect coastal algal blooms, could be expanded. This assessment recommends incorporating a range of future scenarios of improvement plans for current deficiencies in the public health infrastructure to achieve more realistic risk assessments.

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.

Planning for climate change: the need for mechanistic systems-based approaches to study climate change impacts on diarrheal diseases

PubMed Central

Levy, Karen; Zimmerman, Julie; Elliott, Mark; Bartram, Jamie; Carlton, Elizabeth; Clasen, Thomas; Dillingham, Rebecca; Eisenberg, Joseph; Guerrant, Richard; Lantagne, Daniele; Mihelcic, James; Nelson, Kara

2016-01-01

Increased precipitation and temperature variability as well as extreme events related to climate change are predicted to affect the availability and quality of water globally. Already heavily burdened with diarrheal diseases due to poor access to water, sanitation and hygiene facilities, communities throughout the developing world lack the adaptive capacity to sufficiently respond to the additional adversity caused by climate change. Studies suggest that diarrhea rates are positively correlated with increased temperature, and show a complex relationship with precipitation. Although climate change will likely increase rates of diarrheal diseases on average, there is a poor mechanistic understanding of the underlying disease transmission processes and substantial uncertainty surrounding current estimates. This makes it difficult to recommend appropriate adaptation strategies. We review the relevant climate-related mechanisms behind transmission of diarrheal disease pathogens and argue that systems-based mechanistic approaches incorporating human, engineered and environmental components are urgently needed. We then review successful systems-based approaches used in other environmental health fields and detail one modeling framework to predict climate change impacts on diarrheal diseases and design adaptation strategies. PMID:26799810

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

The re-emerging of orf virus infection: A call for surveillance, vaccination and effective control measures.

PubMed

Bala, Jamilu Abubakar; Balakrishnan, Krishnan Nair; Abdullah, Ashwaq Ahmed; Mohamed, Ramlan; Haron, Abd Wahid; Jesse, Faez Firdaus Abdullah; Noordin, Mustapha M; Mohd-Azmi, Mohd Lila

2018-04-28

Orf disease is known to be enzootic among small ruminants in Asia, Africa, and some other parts of the world. The disease caused by orf virus is highly contagious among small ruminant species. Unfortunately, it has been neglected for decades because of the general belief that it only causes a self-limiting disease. On the other hand, in the past it has been reported to cause huge cumulative financial losses in livestock farming. Orf disease is characterized by localized proliferative and persistent skin nodule lesions that can be classified into three forms: generalized, labial and mammary or genitals. It can manifest as benign or malignant types. The later type of orf can remain persistent, often fatal and usually causes a serious outbreak among small ruminant population. Morbidity and mortality rates of orf are higher especially in newly infected kids and lambs. Application of antibiotics together with antipyretic and/or analgesic is highly recommended as a supportive disease management strategy for prevention of subsequent secondary microbial invasion. The presence of various exotic orf virus strains of different origin has been reported in many countries mostly due to poorly controlled cross-border virus transmission. There have been several efforts to develop orf virus vaccines and it was with variable success. The use of conventional vaccines to control orf is a debatable topic due to the concern of short term immunity development. Following re-infection in previously vaccinated animals, it is uncommon to observe the farms involved to experience rapid virus spread and disease outbreak. Meanwhile, cases of zoonosis from infected animals to animal handler are not uncommon. Despite failures to contain the spread of orf virus by the use of conventional vaccines, vaccination of animals with live orf virus is still considered as one of the best choice. The review herein described pertinent issues with regard to the development and use of potential effective vaccines as a control measure against orf virus infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

CREATION OF A MODEL TO PREDICT SURVIVAL IN PATIENTS WITH REFRACTORY COELIAC DISEASE USING A MULTINATIONAL REGISTRY

PubMed Central

Rubio-Tapia, Alberto; Malamut, Georgia; Verbeek, Wieke H.M.; van Wanrooij, Roy L.J.; Leffler, Daniel A.; Niveloni, Sonia I.; Arguelles-Grande, Carolina; Lahr, Brian D.; Zinsmeister, Alan R.; Murray, Joseph A.; Kelly, Ciaran P.; Bai, Julio C.; Green, Peter H.; Daum, Severin; Mulder, Chris J.J.; Cellier, Christophe

2016-01-01

Background Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. Aim To create a prognostic model to estimate survival of patients with refractory coeliac disease. Methods We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap re-sampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. Results The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across 7 centers (range of 11–63 cases per center). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval: 1.38, 3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% confidence interval: 1.22, 6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% confidence interval: 0.61, 0.85). A simple weighted 3-factor risk score was created to estimate 5-year survival. Conclusions Using data from a multinational registry and previously-reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. PMID:27485029

Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

PubMed

Rubio-Tapia, A; Malamut, G; Verbeek, W H M; van Wanrooij, R L J; Leffler, D A; Niveloni, S I; Arguelles-Grande, C; Lahr, B D; Zinsmeister, A R; Murray, J A; Kelly, C P; Bai, J C; Green, P H; Daum, S; Mulder, C J J; Cellier, C

2016-10-01

Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. To create a prognostic model to estimate survival of patients with refractory coeliac disease. We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up. © 2016 John Wiley & Sons Ltd.

Evidence that disease-induced population decline changes genetic structure and alters dispersal patterns in the Tasmanian devil

PubMed Central

Lachish, S; Miller, K J; Storfer, A; Goldizen, A W; Jones, M E

2011-01-01

Infectious disease has been shown to be a major cause of population declines in wild animals. However, there remains little empirical evidence on the genetic consequences of disease-mediated population declines, or how such perturbations might affect demographic processes such as dispersal. Devil facial tumour disease (DFTD) has resulted in the rapid decline of the Tasmanian devil, Sarcophilus harrisii, and threatens to cause extinction. Using 10 microsatellite DNA markers, we compared genetic diversity and structure before and after DFTD outbreaks in three Tasmanian devil populations to assess the genetic consequences of disease-induced population decline. We also used both genetic and demographic data to investigate dispersal patterns in Tasmanian devils along the east coast of Tasmania. We observed a significant increase in inbreeding (FIS pre/post-disease −0.030/0.012, P<0.05; relatedness pre/post-disease 0.011/0.038, P=0.06) in devil populations after just 2–3 generations of disease arrival, but no detectable change in genetic diversity. Furthermore, although there was no subdivision apparent among pre-disease populations (θ=0.005, 95% confidence interval (CI) −0.003 to 0.017), we found significant genetic differentiation among populations post-disease (θ=0.020, 0.010–0.027), apparently driven by a combination of selection and altered dispersal patterns of females in disease-affected populations. We also show that dispersal is male-biased in devils and that dispersal distances follow a typical leptokurtic distribution. Our results show that disease can result in genetic and demographic changes in host populations over few generations and short time scales. Ongoing management of Tasmanian devils must now attempt to maintain genetic variability in this species through actions designed to reverse the detrimental effects of inbreeding and subdivision in disease-affected populations. PMID:20216571

Associations of cause-specific mortality with area level deprivation and travel time to health care in France from 1990 to 2007, a multilevel analysis.

PubMed

Ghosn, Walid; Menvielle, Gwenn; Rican, Stéphane; Rey, Grégoire

2017-08-02

It is now widely accepted that social and physical environment participate in shaping health. While mortality is used to guide public health policies and is considered as a synthetic measure of population health, few studies deals with the contextual features potentially associated with mortality in a representative sample of an entire country. This paper investigates the possible role of area deprivation (FDep99) and travel time to health care on French cause-specific mortality in a proper multilevel setting. The study population was a 1% sample representative of the French population aged from 30 to 79 years in 1990 and followed up until 2007. A frailty Cox model was used to measure individual, contextual effects and spatial variances for several causes of death. The chosen contextual scale was the Zone d'Emploi of 1994 (348 units) which delimits the daily commute of people. The geographical accessibility to health care score was constructed with principal component analysis, using 40 variables of hospital specialties and health practitioners' travel time. The outcomes highlight a positive and significant association between area deprivation and mortality for all causes (HR = 1.24), cancers, cerebrovascular diseases, ischemic heart diseases, and preventable and amenable diseases (HR from 1.14 to 1.29). These contextual associations exhibit no substantial differences by sex except for premature ischemic heart diseases mortality which was much greater in women. Unexpectedly, mortality decreased as the time to reach health care resources increased. Only geographical disparities in cerebrovascular and ischemic heart diseases mortality were explained by compositional and contextual effects. The findings suggest the presence of confounding factors in the association between mortality and travel time to health care, possibly owing to population density and health-selected migration. Although the spatial scale considered to define the context of residence was relatively large, the associations with area deprivation were strong in comparison to the existing literature and significant for almost all the causes of deaths investigated. The broad spectrum of diseases associated with area deprivation and individual education support the idea of a need for a global health policy targeting both individual and territories to reduce social and socio-spatial inequalities.

Prevention of Cardiovascular Disease in Women.

PubMed

Saeed, Anum; Kampangkaew, June; Nambi, Vijay

2017-01-01

Cardiovascular diseases are the leading cause of morbidity and mortality among women worldwide. The pathophysiological basis of cardiovascular health among men and women is not identical. This leads to variable cardiovascular responses to stimulus and presentation of cardiovascular disease symptoms, both of which can have a direct effect on treatment outcomes. Traditionally, the enrollment of women in clinical trials has been minimal, resulting in a lack of gender-specific analysis of clinical trial data and, therefore, the absence of concrete risk factor assessment among women. However, scientific progress in the past decade has identified a spectrum of risk factors for cardiovascular diseases that may be specific to women. These risk factors, which may include menopause, hypertensive disease of pregnancy, and depression, confer additional risk in women besides the traditional risk factors. The current state of knowledge and awareness about these risk factors is suboptimal at this time. Therefore, although the treatment of cardiovascular diseases is similar in both genders, appropriate risk stratification may be limited in women compared to men. The purpose of this review is to describe the recent trends in identifying female-specific risk factors for cardiovascular diseases, their utility in risk stratification, and current pharmacological options for women with regard to cardiovascular disease prevention.

Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?

PubMed Central

Hallett, Mark; Deuschl, Günther; Toni, Ivan; Bloem, Bastiaan R.

2012-01-01

Tremor in Parkinson's disease has several mysterious features. Clinically, tremor is seen in only three out of four patients with Parkinson's disease, and tremor-dominant patients generally follow a more benign disease course than non-tremor patients. Pathophysiologically, tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other tremors. The purpose of this review is to integrate these clinical and pathophysiological features of tremor in Parkinson's disease. We first describe clinical and pathological differences between tremor-dominant and non-tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of tremor. We also discuss a newly proposed ‘dimmer-switch model’ that explains tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger tremor episodes and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we address several important open questions: why resting tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression. PMID:22382359

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition.

PubMed

Murray, Christopher J L; Barber, Ryan M; Foreman, Kyle J; Abbasoglu Ozgoren, Ayse; Abd-Allah, Foad; Abera, Semaw F; Aboyans, Victor; Abraham, Jerry P; Abubakar, Ibrahim; Abu-Raddad, Laith J; Abu-Rmeileh, Niveen M; Achoki, Tom; Ackerman, Ilana N; Ademi, Zanfina; Adou, Arsène K; Adsuar, José C; Afshin, Ashkan; Agardh, Emilie E; Alam, Sayed Saidul; Alasfoor, Deena; Albittar, Mohammed I; Alegretti, Miguel A; Alemu, Zewdie A; Alfonso-Cristancho, Rafael; Alhabib, Samia; Ali, Raghib; Alla, François; Allebeck, Peter; Almazroa, Mohammad A; Alsharif, Ubai; Alvarez, Elena; Alvis-Guzman, Nelson; Amare, Azmeraw T; Ameh, Emmanuel A; Amini, Heresh; Ammar, Walid; Anderson, H Ross; Anderson, Benjamin O; Antonio, Carl Abelardo T; Anwari, Palwasha; Arnlöv, Johan; Arsic Arsenijevic, Valentina S; Artaman, Al; Asghar, Rana J; Assadi, Reza; Atkins, Lydia S; Avila, Marco A; Awuah, Baffour; Bachman, Victoria F; Badawi, Alaa; Bahit, Maria C; Balakrishnan, Kalpana; Banerjee, Amitava; Barker-Collo, Suzanne L; Barquera, Simon; Barregard, Lars; Barrero, Lope H; Basu, Arindam; Basu, Sanjay; Basulaiman, Mohammed O; Beardsley, Justin; Bedi, Neeraj; Beghi, Ettore; Bekele, Tolesa; Bell, Michelle L; Benjet, Corina; Bennett, Derrick A; Bensenor, Isabela M; Benzian, Habib; Bernabé, Eduardo; Bertozzi-Villa, Amelia; Beyene, Tariku J; Bhala, Neeraj; Bhalla, Ashish; Bhutta, Zulfiqar A; Bienhoff, Kelly; Bikbov, Boris; Biryukov, Stan; Blore, Jed D; Blosser, Christopher D; Blyth, Fiona M; Bohensky, Megan A; Bolliger, Ian W; Bora Başara, Berrak; Bornstein, Natan M; Bose, Dipan; Boufous, Soufiane; Bourne, Rupert R A; Boyers, Lindsay N; Brainin, Michael; Brayne, Carol E; Brazinova, Alexandra; Breitborde, Nicholas J K; Brenner, Hermann; Briggs, Adam D; Brooks, Peter M; Brown, Jonathan C; Brugha, Traolach S; Buchbinder, Rachelle; Buckle, Geoffrey C; Budke, Christine M; Bulchis, Anne; Bulloch, Andrew G; Campos-Nonato, Ismael R; Carabin, Hélène; Carapetis, Jonathan R; Cárdenas, Rosario; Carpenter, David O; Caso, Valeria; Castañeda-Orjuela, Carlos A; Castro, Ruben E; Catalá-López, Ferrán; Cavalleri, Fiorella; Çavlin, Alanur; Chadha, Vineet K; Chang, Jung-Chen; Charlson, Fiona J; Chen, Honglei; Chen, Wanqing; Chiang, Peggy P; Chimed-Ochir, Odgerel; Chowdhury, Rajiv; Christensen, Hanne; Christophi, Costas A; Cirillo, Massimo; Coates, Matthew M; Coffeng, Luc E; Coggeshall, Megan S; Colistro, Valentina; Colquhoun, Samantha M; Cooke, Graham S; Cooper, Cyrus; Cooper, Leslie T; Coppola, Luis M; Cortinovis, Monica; Criqui, Michael H; Crump, John A; Cuevas-Nasu, Lucia; Danawi, Hadi; Dandona, Lalit; Dandona, Rakhi; Dansereau, Emily; Dargan, Paul I; Davey, Gail; Davis, Adrian; Davitoiu, Dragos V; Dayama, Anand; De Leo, Diego; Degenhardt, Louisa; Del Pozo-Cruz, Borja; Dellavalle, Robert P; Deribe, Kebede; Derrett, Sarah; Des Jarlais, Don C; Dessalegn, Muluken; Dharmaratne, Samath D; Dherani, Mukesh K; Diaz-Torné, Cesar; Dicker, Daniel; Ding, Eric L; Dokova, Klara; Dorsey, E Ray; Driscoll, Tim R; Duan, Leilei; Duber, Herbert C; Ebel, Beth E; Edmond, Karen M; Elshrek, Yousef M; Endres, Matthias; Ermakov, Sergey P; Erskine, Holly E; Eshrati, Babak; Esteghamati, Alireza; Estep, Kara; Faraon, Emerito Jose A; Farzadfar, Farshad; Fay, Derek F; Feigin, Valery L; Felson, David T; Fereshtehnejad, Seyed-Mohammad; Fernandes, Jefferson G; Ferrari, Alize J; Fitzmaurice, Christina; Flaxman, Abraham D; Fleming, Thomas D; Foigt, Nataliya; Forouzanfar, Mohammad H; Fowkes, F Gerry R; Paleo, Urbano Fra; Franklin, Richard C; Fürst, Thomas; Gabbe, Belinda; Gaffikin, Lynne; Gankpé, Fortuné G; Geleijnse, Johanna M; Gessner, Bradford D; Gething, Peter; Gibney, Katherine B; Giroud, Maurice; Giussani, Giorgia; Gomez Dantes, Hector; Gona, Philimon; González-Medina, Diego; Gosselin, Richard A; Gotay, Carolyn C; Goto, Atsushi; Gouda, Hebe N; Graetz, Nicholas; Gugnani, Harish C; Gupta, Rahul; Gupta, Rajeev; Gutiérrez, Reyna A; Haagsma, Juanita; Hafezi-Nejad, Nima; Hagan, Holly; Halasa, Yara A; Hamadeh, Randah R; Hamavid, Hannah; Hammami, Mouhanad; Hancock, Jamie; Hankey, Graeme J; Hansen, Gillian M; Hao, Yuantao; Harb, Hilda L; Haro, Josep Maria; Havmoeller, Rasmus; Hay, Simon I; Hay, Roderick J; Heredia-Pi, Ileana B; Heuton, Kyle R; Heydarpour, Pouria; Higashi, Hideki; Hijar, Martha; Hoek, Hans W; Hoffman, Howard J; Hosgood, H Dean; Hossain, Mazeda; Hotez, Peter J; Hoy, Damian G; Hsairi, Mohamed; Hu, Guoqing; Huang, Cheng; Huang, John J; Husseini, Abdullatif; Huynh, Chantal; Iannarone, Marissa L; Iburg, Kim M; Innos, Kaire; Inoue, Manami; Islami, Farhad; Jacobsen, Kathryn H; Jarvis, Deborah L; Jassal, Simerjot K; Jee, Sun Ha; Jeemon, Panniyammakal; Jensen, Paul N; Jha, Vivekanand; Jiang, Guohong; Jiang, Ying; Jonas, Jost B; Juel, Knud; Kan, Haidong; Karch, André; Karema, Corine K; Karimkhani, Chante; Karthikeyan, Ganesan; Kassebaum, Nicholas J; Kaul, Anil; Kawakami, Norito; Kazanjan, Konstantin; Kemp, Andrew H; Kengne, Andre P; Keren, Andre; Khader, Yousef S; Khalifa, Shams Eldin A; Khan, Ejaz A; Khan, Gulfaraz; Khang, Young-Ho; Kieling, Christian; Kim, Daniel; Kim, Sungroul; Kim, Yunjin; Kinfu, Yohannes; Kinge, Jonas M; Kivipelto, Miia; Knibbs, Luke D; Knudsen, Ann Kristin; Kokubo, Yoshihiro; Kosen, Soewarta; Krishnaswami, Sanjay; Kuate Defo, Barthelemy; Kucuk Bicer, Burcu; Kuipers, Ernst J; Kulkarni, Chanda; Kulkarni, Veena S; Kumar, G Anil; Kyu, Hmwe H; Lai, Taavi; Lalloo, Ratilal; Lallukka, Tea; Lam, Hilton; Lan, Qing; Lansingh, Van C; Larsson, Anders; Lawrynowicz, Alicia E B; Leasher, Janet L; Leigh, James; Leung, Ricky; Levitz, Carly E; Li, Bin; Li, Yichong; Li, Yongmei; Lim, Stephen S; Lind, Maggie; Lipshultz, Steven E; Liu, Shiwei; Liu, Yang; Lloyd, Belinda K; Lofgren, Katherine T; Logroscino, Giancarlo; Looker, Katharine J; Lortet-Tieulent, Joannie; Lotufo, Paulo A; Lozano, Rafael; Lucas, Robyn M; Lunevicius, Raimundas; Lyons, Ronan A; Ma, Stefan; Macintyre, Michael F; Mackay, Mark T; Majdan, Marek; Malekzadeh, Reza; Marcenes, Wagner; Margolis, David J; Margono, Christopher; Marzan, Melvin B; Masci, Joseph R; Mashal, Mohammad T; Matzopoulos, Richard; Mayosi, Bongani M; Mazorodze, Tasara T; Mcgill, Neil W; Mcgrath, John J; Mckee, Martin; Mclain, Abigail; Meaney, Peter A; Medina, Catalina; Mehndiratta, Man Mohan; Mekonnen, Wubegzier; Melaku, Yohannes A; Meltzer, Michele; Memish, Ziad A; Mensah, George A; Meretoja, Atte; Mhimbira, Francis A; Micha, Renata; Miller, Ted R; Mills, Edward J; Mitchell, Philip B; Mock, Charles N; Mohamed Ibrahim, Norlinah; Mohammad, Karzan A; Mokdad, Ali H; Mola, Glen L D; Monasta, Lorenzo; Montañez Hernandez, Julio C; Montico, Marcella; Montine, Thomas J; Mooney, Meghan D; Moore, Ami R; Moradi-Lakeh, Maziar; Moran, Andrew E; Mori, Rintaro; Moschandreas, Joanna; Moturi, Wilkister N; Moyer, Madeline L; Mozaffarian, Dariush; Msemburi, William T; Mueller, Ulrich O; Mukaigawara, Mitsuru; Mullany, Erin C; Murdoch, Michele E; Murray, Joseph; Murthy, Kinnari S; Naghavi, Mohsen; Naheed, Aliya; Naidoo, Kovin S; Naldi, Luigi; Nand, Devina; Nangia, Vinay; Narayan, K M Venkat; Nejjari, Chakib; Neupane, Sudan P; Newton, Charles R; Ng, Marie; Ngalesoni, Frida N; Nguyen, Grant; Nisar, Muhammad I; Nolte, Sandra; Norheim, Ole F; Norman, Rosana E; Norrving, Bo; Nyakarahuka, Luke; Oh, In-Hwan; Ohkubo, Takayoshi; Ohno, Summer L; Olusanya, Bolajoko O; Opio, John Nelson; Ortblad, Katrina; Ortiz, Alberto; Pain, Amanda W; Pandian, Jeyaraj D; Panelo, Carlo Irwin A; Papachristou, Christina; Park, Eun-Kee; Park, Jae-Hyun; Patten, Scott B; Patton, George C; Paul, Vinod K; Pavlin, Boris I; Pearce, Neil; Pereira, David M; Perez-Padilla, Rogelio; Perez-Ruiz, Fernando; Perico, Norberto; Pervaiz, Aslam; Pesudovs, Konrad; Peterson, Carrie B; Petzold, Max; Phillips, Michael R; Phillips, Bryan K; Phillips, David E; Piel, Frédéric B; Plass, Dietrich; Poenaru, Dan; Polinder, Suzanne; Pope, Daniel; Popova, Svetlana; Poulton, Richie G; Pourmalek, Farshad; Prabhakaran, Dorairaj; Prasad, Noela M; Pullan, Rachel L; Qato, Dima M; Quistberg, D Alex; Rafay, Anwar; Rahimi, Kazem; Rahman, Sajjad U; Raju, Murugesan; Rana, Saleem M; Razavi, Homie; Reddy, K Srinath; Refaat, Amany; Remuzzi, Giuseppe; Resnikoff, Serge; Ribeiro, Antonio L; Richardson, Lee; Richardus, Jan Hendrik; Roberts, D Allen; Rojas-Rueda, David; Ronfani, Luca; Roth, Gregory A; Rothenbacher, Dietrich; Rothstein, David H; Rowley, Jane T; Roy, Nobhojit; Ruhago, George M; Saeedi, Mohammad Y; Saha, Sukanta; Sahraian, Mohammad Ali; Sampson, Uchechukwu K A; Sanabria, Juan R; Sandar, Logan; Santos, Itamar S; Satpathy, Maheswar; Sawhney, Monika; Scarborough, Peter; Schneider, Ione J; Schöttker, Ben; Schumacher, Austin E; Schwebel, David C; Scott, James G; Seedat, Soraya; Sepanlou, Sadaf G; Serina, Peter T; Servan-Mori, Edson E; Shackelford, Katya A; Shaheen, Amira; Shahraz, Saeid; Shamah Levy, Teresa; Shangguan, Siyi; She, Jun; Sheikhbahaei, Sara; Shi, Peilin; Shibuya, Kenji; Shinohara, Yukito; Shiri, Rahman; Shishani, Kawkab; Shiue, Ivy; Shrime, Mark G; Sigfusdottir, Inga D; Silberberg, Donald H; Simard, Edgar P; Sindi, Shireen; Singh, Abhishek; Singh, Jasvinder A; Singh, Lavanya; Skirbekk, Vegard; Slepak, Erica Leigh; Sliwa, Karen; Soneji, Samir; Søreide, Kjetil; Soshnikov, Sergey; Sposato, Luciano A; Sreeramareddy, Chandrashekhar T; Stanaway, Jeffrey D; Stathopoulou, Vasiliki; Stein, Dan J; Stein, Murray B; Steiner, Caitlyn; Steiner, Timothy J; Stevens, Antony; Stewart, Andrea; Stovner, Lars J; Stroumpoulis, Konstantinos; Sunguya, Bruno F; Swaminathan, Soumya; Swaroop, Mamta; Sykes, Bryan L; Tabb, Karen M; Takahashi, Ken; Tandon, Nikhil; Tanne, David; Tanner, Marcel; Tavakkoli, Mohammad; Taylor, Hugh R; Te Ao, Braden J; Tediosi, Fabrizio; Temesgen, Awoke M; Templin, Tara; Ten Have, Margreet; Tenkorang, Eric Y; Terkawi, Abdullah S; Thomson, Blake; Thorne-Lyman, Andrew L; Thrift, Amanda G; Thurston, George D; Tillmann, Taavi; Tonelli, Marcello; Topouzis, Fotis; Toyoshima, Hideaki; Traebert, Jefferson; Tran, Bach X; Trillini, Matias; Truelsen, Thomas; Tsilimbaris, Miltiadis; Tuzcu, Emin M; Uchendu, Uche S; Ukwaja, Kingsley N; Undurraga, Eduardo A; Uzun, Selen B; Van Brakel, Wim H; Van De Vijver, Steven; van Gool, Coen H; Van Os, Jim; Vasankari, Tommi J; Venketasubramanian, N; Violante, Francesco S; Vlassov, Vasiliy V; Vollset, Stein Emil; Wagner, Gregory R; Wagner, Joseph; Waller, Stephen G; Wan, Xia; Wang, Haidong; Wang, Jianli; Wang, Linhong; Warouw, Tati S; Weichenthal, Scott; Weiderpass, Elisabete; Weintraub, Robert G; Wenzhi, Wang; Werdecker, Andrea; Westerman, Ronny; Whiteford, Harvey A; Wilkinson, James D; Williams, Thomas N; Wolfe, Charles D; Wolock, Timothy M; Woolf, Anthony D; Wulf, Sarah; Wurtz, Brittany; Xu, Gelin; Yan, Lijing L; Yano, Yuichiro; Ye, Pengpeng; Yentür, Gökalp K; Yip, Paul; Yonemoto, Naohiro; Yoon, Seok-Jun; Younis, Mustafa Z; Yu, Chuanhua; Zaki, Maysaa E; Zhao, Yong; Zheng, Yingfeng; Zonies, David; Zou, Xiaonong; Salomon, Joshua A; Lopez, Alan D; Vos, Theo

2015-11-28

The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6-6·6), from 65·3 years (65·0-65·6) in 1990 to 71·5 years (71·0-71·9) in 2013, HALE at birth rose by 5·4 years (4·9-5·8), from 56·9 years (54·5-59·1) to 62·3 years (59·7-64·8), total DALYs fell by 3·6% (0·3-7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6-29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition--in which increasing sociodemographic status brings structured change in disease burden--is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. Bill & Melinda Gates Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: quantifying the epidemiological transition

PubMed Central

2015-01-01

Summary Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions. PMID:26321261

Impact of genetic variations in C-C chemokine receptors and ligands on infectious diseases.

PubMed

Qidwai, Tabish; Khan, M Y

2016-10-01

Chemokine receptors and ligands are crucial for extensive immune response against infectious diseases such as malaria, leishmaniasis, HIV and tuberculosis and a wide variety of other diseases. Role of chemokines are evidenced in the activation and regulation of immune cell migration which is important for immune response against diseases. Outcome of disease is determined by complex interaction among pathogen, host genetic variability and surrounding milieu. Variation in expression or function of chemokines caused by genetic polymorphisms could be associated with attenuated immune responses. Exploration of chemokine genetic polymorphisms in therapeutic response, gene regulation and disease outcome is important. Infectious agents in human host alter the expression of chemokines via epigenetic alterations and thus contribute to disease pathogenesis. Although some fragmentary data are available on chemokine genetic variations and their contribution in diseases, no unequivocal conclusion has been arrived as yet. We therefore, aim to investigate the association of CCR5-CCL5 and CCR2-CCL2 genetic polymorphisms with different infectious diseases, transcriptional regulation of gene, disease severity and response to therapy. Furthermore, the role of epigenetics in genes related to chemokines and infectious disease are also discussed. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Models Predictive of Metabolic Syndrome Components in Obese Pediatric Patients.

PubMed

Ortega-Cortes, Rosa; Trujillo, Xóchitl; Hurtado López, Erika Fabiola; López Beltrán, Ana Laura; Colunga Rodríguez, Cecilia; Barrera-de Leon, Juan Carlos; Tlacuilo-Parra, Alberto

2016-01-01

Components of metabolic syndrome (MetS) are complications caused by abdominal obesity and insulin resistance (IR). Diagnosis of MetS by clinical indicators could help to identify patients at risk of cardiovascular disease and type 2 diabetes. We undertook this study to propose predictive indicators of MetS in obese children and adolescents. A cross-sectional study was carried out. After obtaining informed consent and the registration of the study with an institutional research committee, 172 obese patients from an Obesity Clinic, aged 6-15 years, were included. Variables included were waist circumference (WC), glucose, high-density lipoprotein (HDL), triglycerides (TGL), blood pressure, insulin resistance (by homeostatic model assessment HOMA-index), acanthosis nigricans (AN), uric acid, serum glutamic oxaloacetic transaminase (GOT) and alanine transaminase, and hepatic sonogram. International standards for age and sex variables were used. Multivariate analysis was applied. Variables predicted components of MetS in children: HOMA-IR (insulin resistance by HOMA index) was increased by 2.4 in hepatic steatosis, by 0.6 for each unit of SUA (serum uric acid), and by 0.009 for every mg/dL of triglycerides. In adolescents, every cm of waist circumference increased systolic blood pressure by 0.6 mmHg, and each unit of SUA increased it by 2.9 mmHg. Serum uric acid and waist circumference are useful and accessible variables that can predict an increased risk of cardiovascular disease in obese pediatric patients. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Corneal dystrophies

PubMed Central

Klintworth, Gordon K

2009-01-01

The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The designation is imprecise but remains in vogue because of its clinical value. Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (anterior corneal dystrophies), the corneal stroma (stromal corneal dystrophies), or Descemet membrane and the corneal endothelium (posterior corneal dystrophies). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees. Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Knowledge about the responsible genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases (mucopolysaccharidoses, lipidoses, mucolipidoses), and several skin diseases (X-linked ichthyosis, keratosis follicularis spinolosa decalvans). The management of the corneal dystrophies varies with the specific disease. Some are treated medically or with methods that excise or ablate the abnormal corneal tissue, such as deep lamellar endothelial keratoplasty (DLEK) and phototherapeutic keratectomy (PTK). Other less debilitating or asymptomatic dystrophies do not warrant treatment. The prognosis varies from minimal effect on the vision to corneal blindness, with marked phenotypic variability. PMID:19236704

Advanced cell-based modeling of the royal disease: characterization of the mutated F9 mRNA.

PubMed

Martorell, L; Luce, E; Vazquez, J L; Richaud-Patin, Y; Jimenez-Delgado, S; Corrales, I; Borras, N; Casacuberta-Serra, S; Weber, A; Parra, R; Altisent, C; Follenzi, A; Dubart-Kupperschmitt, A; Raya, A; Vidal, F; Barquinero, J

2017-11-01

Essentials The Royal disease (RD) is a form of hemophilia B predicted to be caused by a splicing mutation. We generated an iPSC-based model of the disease allowing mechanistic studies at the RNA level. F9 mRNA analysis in iPSC-derived hepatocyte-like cells showed the predicted abnormal splicing. Mutated F9 mRNA level was very low but we also found traces of wild type transcripts. Background The royal disease is a form of hemophilia B (HB) that affected many descendants of Queen Victoria in the 19th and 20th centuries. It was found to be caused by the mutation F9 c.278-3A>G. Objective To generate a physiological cell model of the disease and to study F9 expression at the RNA level. Methods Using fibroblasts from skin biopsies of a previously identified hemophilic patient bearing the F9 c.278-3A>G mutation and his mother, we generated induced pluripotent stem cells (iPSCs). Both the patient's and mother's iPSCs were differentiated into hepatocyte-like cells (HLCs) and their F9 mRNA was analyzed using next-generation sequencing (NGS). Results and Conclusion We demonstrated the previously predicted aberrant splicing of the F9 transcript as a result of an intronic nucleotide substitution leading to a frameshift and the generation of a premature termination codon (PTC). The F9 mRNA level in the patient's HLCs was significantly reduced compared with that of his mother, suggesting that mutated transcripts undergo nonsense-mediated decay (NMD), a cellular mechanism that degrades PTC-containing mRNAs. We also detected small proportions of correctly spliced transcripts in the patient's HLCs, which, combined with genetic variability in splicing and NMD machineries, could partially explain some clinical variability among affected members of the European royal families who had lifespans above the average. This work allowed the demonstration of the pathologic consequences of an intronic mutation in the F9 gene and represents the first bona fide cellular model of HB allowing the study of rare mutations at the RNA level. © 2017 International Society on Thrombosis and Haemostasis.

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.

Sub-Optimal Treatment of Bacterial Biofilms

PubMed Central

Song, Tianyan; Duperthuy, Marylise; Wai, Sun Nyunt

2016-01-01

Bacterial biofilm is an emerging clinical problem recognized in the treatment of infectious diseases within the last two decades. The appearance of microbial biofilm in clinical settings is steadily increasing due to several reasons including the increased use of quality of life-improving artificial devices. In contrast to infections caused by planktonic bacteria that respond relatively well to standard antibiotic therapy, biofilm-forming bacteria tend to cause chronic infections whereby infections persist despite seemingly adequate antibiotic therapy. This review briefly describes the responses of biofilm matrix components and biofilm-associated bacteria towards sub-lethal concentrations of antimicrobial agents, which may include the generation of genetic and phenotypic variabilities. Clinical implications of bacterial biofilms in relation to antibiotic treatments are also discussed. PMID:27338489

Motoneuron firing in amyotrophic lateral sclerosis (ALS)

PubMed Central

de Carvalho, Mamede; Eisen, Andrew; Krieger, Charles; Swash, Michael

2014-01-01

Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal, and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials. PMID:25294995

Modeling sheep pox disease from the 1994-1998 epidemic in Evros Prefecture, Greece.

PubMed

Malesios, C; Demiris, N; Abas, Z; Dadousis, K; Koutroumanidis, T

2014-10-01

Sheep pox is a highly transmissible disease which can cause serious loss of livestock and can therefore have major economic impact. We present data from sheep pox epidemics which occurred between 1994 and 1998. The data include weekly records of infected farms as well as a number of covariates. We implement Bayesian stochastic regression models which, in addition to various explanatory variables like seasonal and environmental/meteorological factors, also contain serial correlation structure based on variants of the Ornstein-Uhlenbeck process. We take a predictive view in model selection by utilizing deviance-based measures. The results indicate that seasonality and the number of infected farms are important predictors for sheep pox incidence. Copyright © 2014 Elsevier Ltd. All rights reserved.

El Niño and human health.

PubMed Central

Kovats, R. S.

2000-01-01

The El Niño-Southern Oscillation (ENSO) is the best known example of quasi-periodic natural climate variability on the interannual time scale. It comprises changes in sea temperature in the Pacific Ocean (El Niño) and changes in atmospheric pressure across the Pacific Basin (the Southern Oscillation), together with resultant effects on world weather. El Niño events occur at intervals of 2-7 years. In certain countries around the Pacific and beyond, El Niño is associated with extreme weather conditions that can cause floods and drought. Globally it is linked to an increased impact of natural disasters. There is evidence that ENSO is associated with a heightened risk of certain vector-borne diseases in specific geographical areas where weather patterns are linked with the ENSO cycle and disease control is limited. This is particularly true for malaria, but associations are also suggested in respect of epidemics of other mosquito-borne and rodent-borne diseases that can be triggered by extreme weather conditions. Seasonal climate forecasts, predicting the likelihood of weather patterns several months in advance, can be used to provide early indicators of epidemic risk, particularly for malaria. Interdisciplinary research and cooperation are required in order to reduce vulnerability to climate variability and weather extremes. PMID:11019461

Linking genetic and environmental factors in amphibian disease risk

PubMed Central

Savage, Anna E; Becker, Carlos G; Zamudio, Kelly R

2015-01-01

A central question in evolutionary biology is how interactions between organisms and the environment shape genetic differentiation. The pathogen Batrachochytrium dendrobatidis (Bd) has caused variable population declines in the lowland leopard frog (Lithobates yavapaiensis); thus, disease has potentially shaped, or been shaped by, host genetic diversity. Environmental factors can also influence both amphibian immunity and Bd virulence, confounding our ability to assess the genetic effects on disease dynamics. Here, we used genetics, pathogen dynamics, and environmental data to characterize L. yavapaiensis populations, estimate migration, and determine relative contributions of genetic and environmental factors in predicting Bd dynamics. We found that the two uninfected populations belonged to a single genetic deme, whereas each infected population was genetically unique. We detected an outlier locus that deviated from neutral expectations and was significantly correlated with mortality within populations. Across populations, only environmental variables predicted infection intensity, whereas environment and genetics predicted infection prevalence, and genetic diversity alone predicted mortality. At one locality with geothermally elevated water temperatures, migration estimates revealed source–sink dynamics that have likely prevented local adaptation. We conclude that integrating genetic and environmental variation among populations provides a better understanding of Bd spatial epidemiology, generating more effective conservation management strategies for mitigating amphibian declines. PMID:26136822

H syndrome: the first 79 patients.

PubMed

Molho-Pessach, Vered; Ramot, Yuval; Camille, Frances; Doviner, Victoria; Babay, Sofia; Luis, Siekavizza Juan; Broshtilova, Valentina; Zlotogorski, Abraham

2014-01-01

H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3. We sought to investigate the clinical and molecular findings in 79 patients with this disorder. A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature. The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3, with no genotype-phenotype correlation. In the 31 patients described by others, data were collected from the medical literature. H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3-related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Fine-temporal forecasting of outbreak probability and severity: Ross River virus in Western Australia.

PubMed

Koolhof, I S; Bettiol, S; Carver, S

2017-10-01

Health warnings of mosquito-borne disease risk require forecasts that are accurate at fine-temporal resolutions (weekly scales); however, most forecasting is coarse (monthly). We use environmental and Ross River virus (RRV) surveillance to predict weekly outbreak probabilities and incidence spanning tropical, semi-arid, and Mediterranean regions of Western Australia (1991-2014). Hurdle and linear models were used to predict outbreak probabilities and incidence respectively, using time-lagged environmental variables. Forecast accuracy was assessed by model fit and cross-validation. Residual RRV notification data were also examined against mitigation expenditure for one site, Mandurah 2007-2014. Models were predictive of RRV activity, except at one site (Capel). Minimum temperature was an important predictor of RRV outbreaks and incidence at all predicted sites. Precipitation was more likely to cause outbreaks and greater incidence among tropical and semi-arid sites. While variable, mitigation expenditure coincided positively with increased RRV incidence (r 2 = 0·21). Our research demonstrates capacity to accurately predict mosquito-borne disease outbreaks and incidence at fine-temporal resolutions. We apply our findings, developing a user-friendly tool enabling managers to easily adopt this research to forecast region-specific RRV outbreaks and incidence. Approaches here may be of value to fine-scale forecasting of RRV in other areas of Australia, and other mosquito-borne diseases.

Preanalytical Confounding Factors in the Analysis of Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: The Issue of Diurnal Variation

PubMed Central

Cicognola, Claudia; Chiasserini, Davide; Parnetti, Lucilla

2015-01-01

Given the growing use of cerebrospinal fluid (CSF) beta-amyloid (Aβ) and tau as biomarkers for early diagnosis of Alzheimer’s disease (AD), it is essential that the diagnostic procedures are standardized and the results comparable across different laboratories. Preanalytical factors are reported to be the cause of at least 50% of the total variability. Among them, diurnal variability is a key issue and may have an impact on the comparability of the values obtained. The available studies on this issue are not conclusive so far. Fluctuations of CSF biomarkers in young healthy volunteers have been previously reported, while subsequent studies have not confirmed those observations in older subjects, the ones most likely to receive this test. The observed differences in circadian rhythms need to be further assessed not only in classical CSF biomarkers but also in novel forthcoming biomarkers. In this review, the existing data on the issue of diurnal variations of CSF classical biomarkers for AD will be analyzed, also evaluating the available data on new possible biomarkers. PMID:26175714

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.

Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency.

PubMed

Maglione, Paul J; Cols, Montserrat; Cunningham-Rundles, Charlotte

2017-10-05

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches.

Evaluating the performance of infectious disease forecasts: A comparison of climate-driven and seasonal dengue forecasts for Mexico.

PubMed

Johansson, Michael A; Reich, Nicholas G; Hota, Aditi; Brownstein, John S; Santillana, Mauricio

2016-09-26

Dengue viruses, which infect millions of people per year worldwide, cause large epidemics that strain healthcare systems. Despite diverse efforts to develop forecasting tools including autoregressive time series, climate-driven statistical, and mechanistic biological models, little work has been done to understand the contribution of different components to improved prediction. We developed a framework to assess and compare dengue forecasts produced from different types of models and evaluated the performance of seasonal autoregressive models with and without climate variables for forecasting dengue incidence in Mexico. Climate data did not significantly improve the predictive power of seasonal autoregressive models. Short-term and seasonal autocorrelation were key to improving short-term and long-term forecasts, respectively. Seasonal autoregressive models captured a substantial amount of dengue variability, but better models are needed to improve dengue forecasting. This framework contributes to the sparse literature of infectious disease prediction model evaluation, using state-of-the-art validation techniques such as out-of-sample testing and comparison to an appropriate reference model.

Evaluating the performance of infectious disease forecasts: A comparison of climate-driven and seasonal dengue forecasts for Mexico

PubMed Central

Johansson, Michael A.; Reich, Nicholas G.; Hota, Aditi; Brownstein, John S.; Santillana, Mauricio

2016-01-01

Dengue viruses, which infect millions of people per year worldwide, cause large epidemics that strain healthcare systems. Despite diverse efforts to develop forecasting tools including autoregressive time series, climate-driven statistical, and mechanistic biological models, little work has been done to understand the contribution of different components to improved prediction. We developed a framework to assess and compare dengue forecasts produced from different types of models and evaluated the performance of seasonal autoregressive models with and without climate variables for forecasting dengue incidence in Mexico. Climate data did not significantly improve the predictive power of seasonal autoregressive models. Short-term and seasonal autocorrelation were key to improving short-term and long-term forecasts, respectively. Seasonal autoregressive models captured a substantial amount of dengue variability, but better models are needed to improve dengue forecasting. This framework contributes to the sparse literature of infectious disease prediction model evaluation, using state-of-the-art validation techniques such as out-of-sample testing and comparison to an appropriate reference model. PMID:27665707

Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency

PubMed Central

Maglione, Paul J.; Cols, Montserrat

2018-01-01

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches. PMID:28983810

Homozygous single base deletion in TUSC3 causes intellectual disability with developmental delay in an Omani family.

PubMed

Al-Amri, Ahmed; Saegh, Abeer Al; Al-Mamari, Watfa; El-Asrag, Mohammed E; Ivorra, Jose L; Cardno, Alastair G; Inglehearn, Chris F; Clapcote, Steven J; Ali, Manir

2016-07-01

Intellectual disability (ID) is the term used to describe a diverse group of neurological conditions with congenital or juvenile onset, characterized by an IQ score of less than 70 and difficulties associated with limitations in cognitive function and adaptive behavior. The condition can be inherited or caused by environmental factors. The genetic forms are heterogeneous, with mutations in over 500 known genes shown to cause the disorder. We report a consanguineous Omani family in which multiple individuals have ID and developmental delay together with some variably present features including short stature, microcephaly, moderate facial dysmorphism, and congenital malformations of the toes or hands. Homozygosity mapping combined with whole exome next generation sequencing identified a novel homozygous single base pair deletion in TUSC3, c.222delA, p.R74 fs. The mutation segregates with the disease phenotype in a recessive manner and is absent in 60,706 unrelated individuals from various disease-specific and population genetic studies. TUSC3 mutations have been previously identified as causing either syndromic or non-syndromic ID in patients from France, Italy, Iran and Pakistan. This paper supports the previous clinical descriptions of the condition caused by TUSC3 mutations and describes the seventh family with mutations in this gene, thus contributing to the genetic spectrum of mutations. This is the first report of a family from the Arabian peninsula with this form of ID. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Leading causes of death from injury and poisoning by age, sex and urban/rural areas in Tianjin, China 1999-2006.

PubMed

Jiang, Guohong; Choi, Bernard C K; Wang, Dezheng; Zhang, Hui; Zheng, Wenlong; Wu, Tongyu; Chang, Gai

2011-05-01

Injury and poisoning are a growing public health concern in China due to rapid economic growth, which has resulted in many cases with an injury-prone environment, such as overcrowded traffic, booming construction, and work-related stress. This study investigates the distribution and trends of deaths from injury and poisoning in Tianjin, China, by age, sex and urban/rural status, from 1999 to 2006. The study used data from the all-cause mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC). Each death certificate recorded 53 variables. Cause of death was coded using the International Classification of Diseases (ICD). Standardized mortality rates and proportions of deaths were analyzed. Traffic accidents, suicide, poisoning, drowning and fall were the leading causes of fatal injuries in Tianjin from 1999 to 2006. Injury mortality rates were high in males, in rural areas, and in the older age groups. Despite low injury mortality rates, injury accounted for close to 50% of all deaths amongst the 5-29 year age group. Traffic accident mortality rates increased, although not significantly so, during the period from 1999 to 2006. Injury prevention and control is a high public health priority in Tianjin. Our detailed table on the number of deaths by causes of fatal injuries and by age group provides important information to set prevention strategies in the nurseries, schools, workplace and seniors homes. 2009 Elsevier Ltd. All rights reserved.

End stage renal disease in French Guiana (data from R.E.I.N registry): South American or French?

PubMed

Rochemont, Dévi Rita; Meddeb, Mohamed; Roura, Raoul; Couchoud, Cécile; Nacher, Mathieu; Basurko, Célia

2017-06-30

End-Stage renal disease (ESRD) causes considerable morbidity and mortality, and significantly alters patients' quality of life. There are very few published data on this problem in the French Overseas territories. The development of a registry on end stage renal disease in French Guiana in 2011 allowed to describe the magnitude of this problem in the region for the first time. Using data from the French Renal Epidemiology and Information Network registry (R.E.I.N). Descriptive statistics on quantitative and qualitative variables in the registry were performed on prevalent cases and incident cases in 2011, 2012 and 2013. French Guiana has one of the highest ESRD prevalence and incidence in France. The two main causes of ESRD were hypertensive and diabetic nephropathies. The French Guianese population had a different demographic profile (younger, more women, more migrants) than in mainland France. Most patients had at least one comorbidity, predominantly (95.3%) hypertension. In French Guiana dialysis was initiated in emergency for 71.3% of patients versus 33% in France (p < 0.001). These first results give important public health information: i) End stage renal disease has a very high prevalence relative to mainland France ii) Patients have a different demographic profile and enter care late in the course of their renal disease. These data are closer to what is observed in the Caribbean or in Latin America than in Mainland France.

Low abundance of sweat duct Cl− channel CFTR in both healthy and cystic fibrosis athletes with exceptionally salty sweat during exercise

PubMed Central

Haack, Karla K. V.; Pollack, Brian P.; Millard-Stafford, Mindy; McCarty, Nael A.

2011-01-01

To understand potential mechanisms explaining interindividual variability observed in human sweat sodium concentration ([Na+]), we investigated the relationship among [Na+] of thermoregulatory sweat, plasma membrane expression of Na+ and Cl− transport proteins in biopsied human eccrine sweat ducts, and basal levels of vasopressin (AVP) and aldosterone. Lower ductal luminal membrane expression of the Cl− channel cystic fibrosis transmembrane conductance regulator (CFTR) was observed in immunofluorescent staining of sweat glands from healthy young adults identified as exceptionally “salty sweaters” (SS) (n = 6, P < 0.05) and from patients with cystic fibrosis (CF) (n = 6, P < 0.005) compared with ducts from healthy young adults with “typical” sweat [Na+] (control, n = 6). Genetic testing of healthy subjects did not reveal any heterozygotes (“carriers”) for any of the 39 most common disease-causing CFTR mutations in the United States. SS had higher baseline plasma [AVP] compared with control (P = 0.029). Immunostaining to investigate a potential relationship between higher plasma [AVP] (and sweat [Na+]) and ductal membrane aquaporin-5 revealed for all groups a relatively sparse and location-dependent ductal expression of the water channel with localization primarily to the secretory coil. Availability of CFTR for NaCl transport across the ductal membrane appears related to the significant physiological variability observed in sweat salt concentration in apparently healthy humans. At present, a heritable link between healthy salty sweaters and the most prevalent disease-causing CFTR mutations cannot be established. PMID:21228336

Androgen-induced cerebral venous sinus thrombosis in a young body builder: case report

PubMed Central

Sahraian, Mohammad Ali; Mottamedi, Mahmood; Azimi, Amir Reza; Moghimi, Babak

2004-01-01

Background Cerebral venous sinus thrombosis is an infrequent disease with a variety of causes. Pregnancy, puerperium, contraceptive pills and intracranial infections are the most common causes. The patient may present with headache, focal neurological deficits and seizures. The clinical outcome is highly variable and treatment with heparin is advised. Case presentation The patient is a 22 year old male who presented with headache, repeated vomiting and papilledema. He was a bodybuilder doing exercise since 5 years ago, who had used nandrolone decaonoate 25 milligrams intramuscularly during the previous 5 months. Brain MRI and MRV showed superior sagital and transverse sinus thrombosis and extensive investigations did not reveal any known cause. Conclusions We suggested that androgen was the predisposing factor in our patient. Androgens may increase coagulation factors or platelet activity and cause arterial or venous thrombosis. As athletes may hide using androgens it should be considered as a predisposing factor for thrombotic events in such patients. PMID:15579201

Alu element insertion in PKLR gene as a novel cause of pyruvate kinase deficiency in Middle Eastern patients.

PubMed

Lesmana, Harry; Dyer, Lisa; Li, Xia; Denton, James; Griffiths, Jenna; Chonat, Satheesh; Seu, Katie G; Heeney, Matthew M; Zhang, Kejian; Hopkin, Robert J; Kalfa, Theodosia A

2018-03-01

Pyruvate kinase deficiency (PKD) is the most frequent red blood cell enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic hemolytic anemia. Over 250 PKLR-gene mutations have been described, including missense/nonsense, splicing and regulatory mutations, small insertions, small and gross deletions, causing PKD and hemolytic anemia of variable severity. Alu retrotransposons are the most abundant mobile DNA sequences in the human genome, contributing to almost 11% of its mass. Alu insertions have been associated with a number of human diseases either by disrupting a coding region or a splice signal. Here, we report on two unrelated Middle Eastern patients, both born from consanguineous parents, with transfusion-dependent hemolytic anemia, where sequence analysis revealed a homozygous insertion of AluYb9 within exon 6 of the PKLR gene, causing precipitous decrease of PKLR RNA levels. This Alu element insertion consists a previously unrecognized mechanism underlying pathogenesis of PKD. © 2017 Wiley Periodicals, Inc.

Rare Copy Number Variants Are a Common Cause of Short Stature

PubMed Central

Zahnleiter, Diana; Uebe, Steffen; Ekici, Arif B.; Hoyer, Juliane; Wiesener, Antje; Wieczorek, Dagmar; Kunstmann, Erdmute; Reis, André; Doerr, Helmuth-Guenther; Rauch, Anita; Thiel, Christian T.

2013-01-01

Human growth has an estimated heritability of about 80%–90%. Nevertheless, the underlying cause of shortness of stature remains unknown in the majority of individuals. Genome-wide association studies (GWAS) showed that both common single nucleotide polymorphisms and copy number variants (CNVs) contribute to height variation under a polygenic model, although explaining only a small fraction of overall genetic variability in the general population. Under the hypothesis that severe forms of growth retardation might also be caused by major gene effects, we searched for rare CNVs in 200 families, 92 sporadic and 108 familial, with idiopathic short stature compared to 820 control individuals. Although similar in number, patients had overall significantly larger CNVs (p-value<1×10−7). In a gene-based analysis of all non-polymorphic CNVs>50 kb for gene function, tissue expression, and murine knock-out phenotypes, we identified 10 duplications and 10 deletions ranging in size from 109 kb to 14 Mb, of which 7 were de novo (p<0.03) and 13 inherited from the likewise affected parent but absent in controls. Patients with these likely disease causing 20 CNVs were smaller than the remaining group (p<0.01). Eleven (55%) of these CNVs either overlapped with known microaberration syndromes associated with short stature or contained GWAS loci for height. Haploinsufficiency (HI) score and further expression profiling suggested dosage sensitivity of major growth-related genes at these loci. Overall 10% of patients carried a disease-causing CNV indicating that, like in neurodevelopmental disorders, rare CNVs are a frequent cause of severe growth retardation. PMID:23516380

Detection of c. -32T>G (IVS1-13T>G) mutation of Pompe disease by real-time PCR in dried blood spot specimen.

PubMed

Bobillo Lobato, Joaquin; Sánchez Peral, Blas A; Durán Parejo, Pilar; Jiménez Jiménez, Luis M

2013-03-15

Pompe disease, or acid maltase deficiency, is a genetic muscle disorder caused by mutations in the gene encoding the acid alpha-glucosidase (GAA) enzyme, which is essential for the degradation of glycogen to glucose in lysosomes. The wide clinical variability is resulted from genetic heterogeneity, and many different mutations of the GAA gene have been reported. Some of these mutations are associated with specific phenotypes, such as the c. -32T>G (IVS1-13T>G) mutation seen in late-onset Pompe disease. We used a real-time PCR, after genomic DNA extraction isolated from DBS (dried blood spots) and PCR amplification. Our results successfully detected in controls and patients have been 100% concordant with sequencing results. This assay combines simple sample processing and rapid analysis and it allows to detect the patients with a milder form and slower progression of this disease with a high reliability. Copyright © 2013 Elsevier B.V. All rights reserved.

Precision medicine and drug development in Alzheimer's disease: The importance of sexual dimorphism and patient stratification.

PubMed

Hampel, Harald; Vergallo, Andrea; Giorgi, Filippo Sean; Kim, Seung Hyun; Depypere, Herman; Graziani, Manuela; Saidi, Amira; Nisticò, Robert; Lista, Simone

2018-06-12

Neurodegenerative diseases (ND) are among the leading causes of disability and mortality. Considerable sex differences exist in the occurrence of the various manifestations leading to cognitive decline. Alzheimer's disease (AD) exhibits substantial sexual dimorphisms and disproportionately affects women. Women have a higher life expectancy compared to men and, consequently, have more lifespan to develop AD. The emerging precision medicine and pharmacology concepts - taking into account the individual genetic and biological variability relevant for disease risk, prevention, detection, diagnosis, and treatment - are expected to substantially enhance our knowledge and management of AD. Stratifying the affected individuals by sex and gender is an important basic step towards personalization of scientific research, drug development, and care. We hypothesize that sex and gender differences, extending from genetic to psychosocial domains, are highly relevant for the understanding of AD pathophysiology, and for the conceptualization of basic/translational research and for clinical therapy trial design. Copyright © 2018 Elsevier Inc. All rights reserved.

New Insights into Human Cryptosporidiosis

PubMed Central

Clark, Douglas P.

1999-01-01

Cryptosporidium parvum is an important cause of diarrhea worldwide. Cryptosporidium causes a potentially life-threatening disease in people with AIDS and contributes significantly to morbidity among children in developing countries. In immunocompetent adults, Cryptosporidium is often associated with waterborne outbreaks of acute diarrheal illness. Recent studies with human volunteers have indicated that Cryptosporidium is highly infectious. Diagnosis of infection with this parasite has relied on identification of acid-fast oocysts in stool; however, new immunoassays or PCR-based assays may increase the sensitivity of detection. Although the mechanism by which Cryptosporidium causes diarrhea is still poorly understood, the parasite and the immune response to it probably combine to impair absorption and enhance secretion within the intestinal tract. Important genetic studies suggest that humans can be infected by at least two genetically distinct types of Cryptosporidium, which may vary in virulence. This may, in part, explain the clinical variability seen in patients with cryptosporidiosis. PMID:10515902

Minimal Change Disease

PubMed Central

Massella, Laura; Ruggiero, Barbara; Emma, Francesco

2017-01-01

Minimal change disease (MCD) is a major cause of idiopathic nephrotic syndrome (NS), characterized by intense proteinuria leading to edema and intravascular volume depletion. In adults, it accounts for approximately 15% of patients with idiopathic NS, reaching a much higher percentage at younger ages, up to 70%–90% in children >1 year of age. In the pediatric setting, a renal biopsy is usually not performed if presentation is typical and the patient responds to therapy with oral prednisone at conventional doses. Therefore, in this setting steroid-sensitive NS can be considered synonymous with MCD. The pathologic hallmark of disease is absence of visible alterations by light microscopy and effacement of foot processes by electron microscopy. Although the cause is unknown and it is likely that different subgroups of disease recognize a different pathogenesis, immunologic dysregulation and modifications of the podocyte are thought to synergize in altering the integrity of the glomerular basement membrane and therefore determining proteinuria. The mainstay of therapy is prednisone, but steroid-sensitive forms frequently relapse and this leads to a percentage of patients requiring second-line steroid-sparing immunosuppression. The outcome is variable, but forms of MCD that respond to steroids usually do not lead to chronic renal damage, whereas forms that are unresponsive to steroids may subsequently reveal themselves as FSGS. However, in a substantial number of patients the disease is recurrent and requires long-term immunosuppression, with significant morbidity because of side effects. Recent therapeutic advances, such as the use of anti-CD20 antibodies, have provided long-term remission off-therapy and suggest new hypotheses for disease pathogenesis. PMID:27940460

An overview of Brucellosis.

PubMed

Haque, N; Bari, M S; Hossain, M A; Muhammad, N; Ahmed, S; Rahman, A; Hoque, S M; Islam, A

2011-10-01

Brucellosis is the most important zoonotic disease caused by Brucella species comprising Gram negative, facultative, intracellular pathogens. The true incidence of human brucellosis is unknown for most countries of the world including Bangladesh. But brucellosis is not uncommon in our country. Due to its increasing incidence in many countries of the world it is an important issue now days. Domestic animals such as cattle, goats, sheep, pigs, camel, buffalo and dogs serve as a reservoir hosts. Transmission of brucellosis to humans occurs through the consumption of infected, unpasteurized animal milk and milk products, through direct contact with infected animal parts, through ruptures of skin and mucous membranes and through the inhalation of infected aerosolized particles. Due to variability of clinical features and limited availability of laboratory facilities, the disease remains largely under-reported. Early and specific diagnosis is important to ensure a favourable outcome regarding this zoonotic disease.

Environmental Issues in Thyroid Diseases.

PubMed

Ferrari, Silvia Martina; Fallahi, Poupak; Antonelli, Alessandro; Benvenga, Salvatore

2017-01-01

Environmental factors are determinant for the appearance of autoimmune thyroid diseases (AITD) in susceptible subjects. Increased iodine intake, selenium, and vitamin D deficiency, exposure to radiation, from nuclear fallout or due to medical radiation, are environmental factors increasing AITD. Cigarette smoking is associated with Graves' disease and Graves' ophthalmopathy, while it decreases the risk of hypothyroidism and thyroid autoimmunity. Viral infections are important environmental factors in the pathogenesis of AITD, too, particularly human parvovirus B19 (EVB19) and hepatitis C virus. Among the many chemical contaminants, halogenated organochlorines and pesticides variably disrupt thyroid function. Polychlorinated biphenyls and their metabolites and polybrominated diethyl ethers bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Among drugs, interferon- and iodine-containing drugs have been associated with AITD. Moreover intestinal dysbiosis causes autoimmune thyroiditis. To reduce the risk to populations and also in each patient, it is necessary to comprehend the association between environmental agents and thyroid dysfunction.

Variation in recombination rate may bias human genetic disease mapping studies.

PubMed

Boyle, A Susannah; Noor, Mohamed A F

2004-11-01

The availability of the human genome sequence and variability information (as from the International HapMap project) will enhance our ability to map genetic disorders and choose targets for therapeutic intervention. However, several factors, such as regional variation in recombination rate, can bias conclusions from genetic mapping studies. Here, we examine the impact of regional variation in recombination rate across the human genome. Through computer simulations and literature surveys, we conclude that genetic disorders have been mapped to regions of low recombination more often than expected if such diseases were randomly distributed across the genome. This concentration in low recombination regions may be an artifact, and disorders appearing to be caused by a few genes of large effect may be polygenic. Future genetic mapping studies should be conscious of this potential complication by noting the regional recombination rate of regions implicated in diseases.

Parenteral nutrition-associated liver disease and lipid emulsions.

PubMed

Zugasti Murillo, Ana; Petrina Jáuregui, Estrella; Elizondo Armendáriz, Javier

2015-01-01

Parenteral nutrition-associated liver disease (PNALD) is a particularly important problem in patients who need this type of nutritional support for a long time. Prevalence of the condition is highly variable depending on the series, and its clinical presentation is different in adults and children. The etiology of PNALD is not well defined, and participation of several factors at the same time has been suggested. When a bilirubin level >2 mg/dl is detected for a long time, other causes of liver disease should be ruled out and risk factors should be minimized. The composition of lipid emulsions used in parenteral nutrition is one of the factors related to PNALD. This article reviews the different types of lipid emulsions and the potential benefits of emulsions enriched with omega-3 fatty acids. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Infant mortality in Novo Hamburgo: associated factors and cardiovascular causes.

PubMed

Brum, Camila de Andrade; Stein, Airton Tetelbom; Pellanda, Lucia Campos

2015-04-01

Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables 'age at death', 'gestational age' and 'birth weight'. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

PNPLA3 genetic variation in alcoholic steatosis and liver disease progression

PubMed Central

Hampe, Jochen; Trépo, Eric; Datz, Christian; Romeo, Stefano

2015-01-01

Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations. Although carriership of one or both mutated PNPLA3 alleles does not explain the entire liver phenotypic variability in drinkers, it clearly represents one of the strongest single genetic modulators in a complex trait such as ALD. As more genetic data supporting its important role aggregates, novel insight as to PNPLA3’s function and that of its genetic variation in liver injury is unveiled pointing to an important novel pathway in alcohol-mediated hepatic lipid turnover with strong implications on inflammation, extra cellular matrix remodelling, and hepatocarcinogenesis. Future study shall decipher whether the gathered knowledge can be translated into therapeutic benefits of patients. PMID:26151055

Molecular pathogenesis of sporadic prion diseases in man

PubMed Central

Safar, Jiri G.

2012-01-01

The yeast, fungal and mammalian prions determine heritable and infectious traits that are encoded in alternative conformations of proteins. They cause lethal sporadic, familial and infectious neurodegenerative conditions in man, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic (s)CJD. Recent advances in amplification and detection of prions led to considerable optimism that early and possibly preclinical diagnosis and therapy might become a reality. Although several drugs have already been tested in small numbers of sCJD patients, there is no clear evidence of any agent’s efficacy. Therefore, it remains crucial to determine the full spectrum of sCJD prion strains and the conformational features in the pathogenic human prion protein governing replication of sCJD prions. Research in this direction is essential for the rational development of diagnostic as well as therapeutic strategies. Moreover, there is growing recognition that fundamental processes involved in human prion propagation – intercellular induction of protein misfolding and seeded aggregation of misfolded host proteins – are of far wider significance. This insight leads to new avenues of research in the ever-widening spectrum of age-related human neurodegenerative diseases that are caused by protein misfolding and that pose a major challenge for healthcare. PMID:22421210

Development of a waterborne challenge model for Flavobacterium psychrophilum.

PubMed

Long, Amy; Fehringer, Tyson R; LaFrentz, Benjamin R; Call, Douglas R; Cain, Kenneth D

2014-10-01

Flavobacterium psychrophilum is the causative agent of bacterial coldwater disease and can cause significant mortality in salmonid aquaculture. To better evaluate disease prevention or treatment methods for F. psychrophilum in the laboratory, a waterborne challenge model that mimics a natural outbreak is needed. Here we report on the development of a waterborne challenge model for F. psychrophilum in which we incorporated variables that may influence challenge success: specifically, scarification prior to bacterial exposure and culture of F. psychrophilum under iron-limited culture conditions to potentially increase the probability of establishing disease. Additionally, two F. psychrophilum strains, CSF 259-93 and THC 02-90, were used in this model to test whether there were virulence differences between strains. Mortality was significantly higher in scarred fish than unscarred fish (81.5 vs. 19.4%), supporting the hypothesis that disruptions in the dermal layer enhance mortality in F. psychrophilum waterborne challenges. Although mortality differences were not significant between iron-replete and iron-limited treatments, mortality was high overall (> 30%). There was a significant difference in mortality between CSF 259-93 and THC 02-90 treatments, although both strains caused high mortality in injection challenges. In conclusion, this waterborne challenge model can be used to evaluate potential disease prevention and treatment methods. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Autonomic deficit not the cause of death in West Nile virus neurological disease.

PubMed

Wang, Hong; Siddharthan, Venkatraman; Hall, Jeffery O; Morrey, John D

2014-02-01

Some West Nile virus (WNV)-infected patients have been reported to manifest disease signs consistent with autonomic dysfunction. Moreover, WNV infection in hamsters causes reduced electromyography amplitudes of the gastrointestinal tract and diaphragm, and they have reduced heart rate variability (HRV), a read-out for the parasympathetic autonomic function. HRV was measured in both hamsters and mice using radiotelemetry to identify autonomic deficits. To identify areas of WNV infection within the medulla oblongata mapping to the dorsal motor nucleus of vagus (DMNV) and the nucleus ambiguus (NA), fluorogold dye was injected into the cervical trunk of the vagus nerve of hamsters. As a measurement of the loss of parasympathetic function, tachycardia was monitored contiguously over the time course of the disease. Decrease of HRV did not occur in all animals that died, which is not consistent with autonomic function being the mechanism of death. Fluorogold-stained cells in the DMNV were not stained for WNV envelope protein. Fourteen percent of WNV-stained cells were co-localized with fluorogold-stained cells in the NA. These data, however, did not suggest a fatal loss of autonomic functions because tachycardia was not observed in WNV-infected hamsters. Parasympathetic autonomic function deficit was not a likely mechanism of death in WNV-infected rodents and possibly in human patients with fatal WN neurological disease.

Population-based cohort study of outcomes following cholecystectomy for benign gallbladder diseases.

PubMed

2016-11-01

The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all-cause 30-day readmissions and complications in a prospective population-based cohort. Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all-cause 30-day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two-level hierarchical structure with patients (level 1) nested within hospitals (level 2). Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics. © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

Molecular determination of glutaric aciduria type I in individuals from southwest Iran.

PubMed

Baradaran, Masumeh; Galehdari, Hamid; Aminzadeh, Majid; Azizi Malmiri, Reza; Tangestani, Raheleh; Karimi, Zahra

2014-09-01

Glutaric Aciduria type 1 (GA1) is a metabolic inborn error and is characterized by increasing excursion of glutaric acid and its derivates, presented in microcephaly and dystonia. The disease is resulted from mutational inactivation in the GCDH gene encoding the glutaryl-CoA dehydrogenase. The defective enzyme causes the accumulation of an excessive level of intermediate breakdown products that leads to the brain damage. In spite of the clinical features, diagnosis of GAI has been often confusing, because of variability in the clinical manifestations of patients. Early diagnosis and treatment can though prevent irreversible disease progression and consequent brain damage; otherwise the affected individuals will die in their first decade of lives. The GCDH gene was also analyzed to (detect or identify) disease causing mutations using gene amplification and direct sequencing in 18 patients. Among 18 patients, 10 patients (55.5%) were homozygous or compounded heterozygous for the recurrent mutation E181Q, three patients (16.7%) were homozygous for the known mutation R402Q and one patient (5.6%) was compound heterozygous for S255L. All three detected missense mutations are pathogenic, which cause structural changes in the binding site and tetramerization or functional deficiency. Four other individuals (22.2%) with a preliminary diagnosis of GAI were negative for any pathogenic mutations. Most GA1 affected persons in southwest Iran are with Persian ethnicity and the most common mutation in Khuzestan Province is prominent in comparison to  previous reports from Iran.

A novel regulatory defect in the branched-chain α-keto acid dehydrogenase complex due to a mutation in the PPM1K gene causes a mild variant phenotype of maple syrup urine disease.

PubMed

Oyarzabal, Alfonso; Martínez-Pardo, Mercedes; Merinero, Begoña; Navarrete, Rosa; Desviat, Lourdes R; Ugarte, Magdalena; Rodríguez-Pombo, Pilar

2013-02-01

This article describes a hitherto unreported involvement of the phosphatase PP2Cm, a recently described member of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD). The disease-causing mutation was identified in a patient with a mild variant phenotype, involving a gene not previously associated with MSUD. SNP array-based genotyping showed a copy-neutral homozygous pattern for chromosome 4 compatible with uniparental isodisomy. Mutation analysis of the candidate gene, PPM1K, revealed a homozygous c.417_418delTA change predicted to result in a truncated, unstable protein. No PP2Cm mutant protein was detected in immunocytochemical or Western blot expression analyses. The transient expression of wild-type PPM1K in PP2Cm-deficient fibroblasts recovered 35% of normal BCKDH activity. As PP2Cm has been described essential for cell survival, apoptosis and metabolism, the impact of its deficiency on specific metabolic stress variables was evaluated in PP2Cm-deficient fibroblasts. Increases were seen in ROS levels along with the activation of specific stress-signaling MAP kinases. Similar to that described for the pyruvate dehydrogenase complex, a defect in the regulation of BCKDH caused the aberrant metabolism of its substrate, contributing to the patient's MSUD phenotype--and perhaps others. © 2012 WILEY PERIODICALS, INC.

Geographical distribution of Culicoides (DIPTERA: CERATOPOGONIDAE) in mainland Portugal: Presence/absence modelling of vector and potential vector species.

PubMed

Ramilo, David W; Nunes, Telmo; Madeira, Sara; Boinas, Fernando; da Fonseca, Isabel Pereira

2017-01-01

Vector-borne diseases are not only accounted responsible for their burden on human health-care systems, but also known to cause economic constraints to livestock and animal production. Animals are affected directly by the transmitted pathogens and indirectly when animal movement is restricted. Distribution of such diseases depends on climatic and social factors, namely, environmental changes, globalization, trade and unplanned urbanization. Culicoides biting midges are responsible for the transmission of several pathogenic agents with relevant economic impact. Due to a fragmentary knowledge of their ecology, occurrence is difficult to predict consequently, limiting the control of these arthropod vectors. In order to understand the distribution of Culicoides species, in mainland Portugal, data collected during the National Entomologic Surveillance Program for Bluetongue disease (2005-2013), were used for statistical evaluation. Logistic regression analysis was preformed and prediction maps (per season) were obtained for vector and potentially vector species. The variables used at the present study were selected from WorldClim (two climatic variables) and CORINE databases (twenty-two land cover variables). This work points to an opposite distribution of C. imicola and species from the Obsoletus group within mainland Portugal. Such findings are evidenced in autumn, with the former appearing in Central and Southern regions. Although appearing northwards, on summer and autumn, C. newsteadi reveals a similar distribution to C. imicola. The species C. punctatus appears in all Portuguese territory throughout the year. Contrary, C. pulicaris is poorly caught in all areas of mainland Portugal, being paradoxical present near coastal areas and higher altitude regions.

Geographical distribution of Culicoides (DIPTERA: CERATOPOGONIDAE) in mainland Portugal: Presence/absence modelling of vector and potential vector species

PubMed Central

Madeira, Sara; Boinas, Fernando; da Fonseca, Isabel Pereira

2017-01-01

Vector-borne diseases are not only accounted responsible for their burden on human health-care systems, but also known to cause economic constraints to livestock and animal production. Animals are affected directly by the transmitted pathogens and indirectly when animal movement is restricted. Distribution of such diseases depends on climatic and social factors, namely, environmental changes, globalization, trade and unplanned urbanization. Culicoides biting midges are responsible for the transmission of several pathogenic agents with relevant economic impact. Due to a fragmentary knowledge of their ecology, occurrence is difficult to predict consequently, limiting the control of these arthropod vectors. In order to understand the distribution of Culicoides species, in mainland Portugal, data collected during the National Entomologic Surveillance Program for Bluetongue disease (2005–2013), were used for statistical evaluation. Logistic regression analysis was preformed and prediction maps (per season) were obtained for vector and potentially vector species. The variables used at the present study were selected from WorldClim (two climatic variables) and CORINE databases (twenty-two land cover variables). This work points to an opposite distribution of C. imicola and species from the Obsoletus group within mainland Portugal. Such findings are evidenced in autumn, with the former appearing in Central and Southern regions. Although appearing northwards, on summer and autumn, C. newsteadi reveals a similar distribution to C. imicola. The species C. punctatus appears in all Portuguese territory throughout the year. Contrary, C. pulicaris is poorly caught in all areas of mainland Portugal, being paradoxical present near coastal areas and higher altitude regions. PMID:28683145

The longitudinal impact of depression on disability in Parkinson disease.

PubMed

Pontone, Gregory M; Bakker, Catherine C; Chen, Shaojie; Mari, Zoltan; Marsh, Laura; Rabins, Peter V; Williams, James R; Bassett, Susan S

2016-05-01

Depression in Parkinson disease (PD) is a common problem that worsens quality of life and causes disability. However, little is known about the longitudinal impact of depression on disability in PD. This study examined the association between disability and DSM-IV-TR depression status across six years. Longitudinal cohort study with assessments at study entry, year two, four, and six conducted in the Morris K. Udall Parkinson Disease Research Center. Recruitment totaled 137 adult men and women with idiopathic PD in which up to six years of data on demographic, motor, and non-motor variables was collected. Movement disorder specialists used the structured interview for DSM-IV-TR depressive disorders and the Northwestern Disability Scale to assess depression and disability. A generalized linear mixed model was fitted with Northwestern Disability Scale score as the dependent variable to determine the effect of baseline depression status on disability. A total of 43 participants were depressed at baseline compared to 94 without depression. Depressed participants were more likely to be female, were less educated, were less likely to take dopamine agonists, and more likely to have motor fluctuations. Controlling for these variables, symptomatic depression predicted greater disability compared to both never depressed (p = 0.0133) and remitted depression (p = 0.0009). Disability associated with symptomatic depression at baseline was greater over the entire six-year period compared to participants with remitted depressive episodes or who were never depressed. Persisting depression is associated with a long-term adverse impact on daily functioning in PD. Adequate treatment or spontaneous remission of depression improves ADL function. Copyright © 2015 John Wiley & Sons, Ltd.

Hematology and biochemistry of aging-evidence of "anemia of the elderly" in old dogs.

PubMed

Radakovich, Lauren B; Pannone, Stephen C; Truelove, Matthew P; Olver, Christine S; Santangelo, Kelly S

2017-03-01

Effects of aging on hematologic and biochemical variables are well described in people. Anemia of the elderly is attributed to iron deficiency, anemia of chronic disease, chronic kidney disease, myelodysplasia, or idiopathic causes. Limited studies have examined these variables in aging dogs, but they have typically examined single breeds in research settings. The objective of this study was to identify differences in CBC and biochemistry values between adult and aged dogs of many breeds. Dogs presenting for wellness examinations and minor dental/elective surgeries that were otherwise clinically healthy were retrospectively identified. Dogs were categorized by age: adult (1-7.9 years), senior (8-11.9 years), and geriatric (12+ years). Standard CBC and biochemistry data were collated. Asian breeds, Greyhounds, and dogs with data indicating overt underlying disease were excluded. The Kruskal-Wallis test was used to compare groups with statistical significance set at P ≤ .05. Hematocrit, MCV, and serum iron decreased with age, indicating possible iron-restricted erythropoiesis (IRE), due to iron deficiency or low-grade chronic inflammation. Total proteins, globulins, and platelet counts increased with age while albumin decreased, suggesting low-grade inflammation. Urea was increased in older dogs without a concurrent increase in creatinine, which points toward gastrointestinal bleeding or dehydration. Clinically healthy, aging dogs have changes in laboratory variables that indicate altered physiologies compared to younger adult animals, including evidence of IRE, inflammation, and potential gastrointestinal bleeding, suggesting a similar trend to that of elderly human beings. Future studies will examine markers of iron metabolism and inflammation in aging dogs. © 2017 American Society for Veterinary Clinical Pathology.

Climate and environmental change drives Ixodes ricinus geographical expansion at the northern range margin

PubMed Central

2014-01-01

Background 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. Methods 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. Results 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. Conclusions 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. PMID:24401487

Burden of disease and economic evaluation of healthcare interventions: are we investigating what really matters?

PubMed

Catalá-López, Ferrán; García-Altés, Anna; Alvarez-Martín, Elena; Gènova-Maleras, Ricard; Morant-Ginestar, Consuelo; Parada, Antoni

2011-04-13

The allocation of limited available healthcare resources demands an agreed rational allocation principle and the consequent priority setting. We assessed the association between economic evaluations of healthcare interventions published in Spain (1983-2008) and the disease burden in the population. Electronic databases (e.g., PubMed/MEDLINE, SCOPUS, ISI Web of Knowledge, CRD, IME, IBECS) and reports from health technology assessment agencies were systematically reviewed. For each article, multiple variables were recorded such as: year and journal of publication, type of study, health intervention targetted, perspective of analysis, type of costs and sources of information, first author's affiliation, explicit recommendations aimed at decision-making, and the main disease cause to which the intervention was addressed. The following disease burden measures were calculated: years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs), and mortality by cause. Correlation and linear regression models were fitted. Four hundred and seventy-seven economic evaluations were identified. Cardiovascular diseases (15.7%), infectious diseases (15.3%), malignant neoplasms (13.2%), and neuropsychiatric diseases (9.6%) were the conditions most commonly addressed. Accidents and injuries, congenital anomalies, oral conditions, nutritional deficiencies and other neoplasms were the categories with a lowest number of studies (0.6% for each of them). For the main disease categories (n = 20), a correlation was seen with: mortality 0.67 (p = 0.001), DALYs 0.63 (p = 0.003), YLLs 0.54 (p = 0.014), and YLDs 0.51 (p = 0.018). By disease sub-categories (n = 51), the correlations were generally low and non statistically significant. Examining discrepancies between economic evaluations in particular diseases and the overall burden of disease helps shed light on whether there are potentially over- and under-investigated areas. The approach taken could help policy-makers understand whether resources for economic evaluation are being allocated by using summary measures of population health.

Burden of disease and economic evaluation of healthcare interventions: are we investigating what really matters?

PubMed Central

2011-01-01

Background The allocation of limited available healthcare resources demands an agreed rational allocation principle and the consequent priority setting. We assessed the association between economic evaluations of healthcare interventions published in Spain (1983-2008) and the disease burden in the population. Methods Electronic databases (e.g., PubMed/MEDLINE, SCOPUS, ISI Web of Knowledge, CRD, IME, IBECS) and reports from health technology assessment agencies were systematically reviewed. For each article, multiple variables were recorded such as: year and journal of publication, type of study, health intervention targetted, perspective of analysis, type of costs and sources of information, first author's affiliation, explicit recommendations aimed at decision-making, and the main disease cause to which the intervention was addressed. The following disease burden measures were calculated: years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs), and mortality by cause. Correlation and linear regression models were fitted. Results Four hundred and seventy-seven economic evaluations were identified. Cardiovascular diseases (15.7%), infectious diseases (15.3%), malignant neoplasms (13.2%), and neuropsychiatric diseases (9.6%) were the conditions most commonly addressed. Accidents and injuries, congenital anomalies, oral conditions, nutritional deficiencies and other neoplasms were the categories with a lowest number of studies (0.6% for each of them). For the main disease categories (n = 20), a correlation was seen with: mortality 0.67 (p = 0.001), DALYs 0.63 (p = 0.003), YLLs 0.54 (p = 0.014), and YLDs 0.51 (p = 0.018). By disease sub-categories (n = 51), the correlations were generally low and non statistically significant. Conclusions Examining discrepancies between economic evaluations in particular diseases and the overall burden of disease helps shed light on whether there are potentially over- and under-investigated areas. The approach taken could help policy-makers understand whether resources for economic evaluation are being allocated by using summary measures of population health. PMID:21489236

[Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia].

PubMed

Hayashi, Yukiko

2013-01-01

Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) is an autosomal dominant disease caused by mutations in the VCP gene. VCP encodes a well-conserved multifunctional protein, valosin containing protein (VCP), which has important roles in protein quality control via proteasome and autophagy, protein aggregation, quality control of mitochondria, cell proliferation, and so on. Clinically, muscle weakness is the most common symptom of which disease onset is around 40 years. Affected muscles are variable, and the patients are sometimes diagnosed as limb girdle muscular dystrophy or GNE myopathy. Muscle pathology shows characteristic features including cytoplasmic/nuclear inclusions, rimmed vacuoles, and disorganized myofibrills, together with neurogenic changes. Paget's disease of bone is reported to be observed in a half of the patients around the age of 40 years, but less common in Japanese patients. Frontotemporal dementia is seen around one third of the patients which appears nearly 10 years later than muscle or bone disease. In addition to cognitive dysfunctions, motor neuron involvement and cerebellar signs were also seen in our series. IBMPFD is not so rare disease as previously thought, but complicate clinical findings may make its diagnosis difficult.

Land Use, Macroalgae, and a Tumor-Forming Disease in Marine Turtles

PubMed Central

Van Houtan, Kyle S.; Hargrove, Stacy K.; Balazs, George H.

2010-01-01

Wildlife diseases are an increasing concern for endangered species conservation, but their occurrence, causes, and human influences are often unknown. We analyzed 3,939 records of stranded Hawaiian green sea turtles (Chelonia mydas) over 28 years to understand fibropapillomatosis, a tumor-forming disease linked to a herpesvirus. Turtle size is a consistent risk factor and size-standardized models revealed considerable spatial and temporal variability. The disease peaked in some areas in the 1990s, in some regions rates remained constant, and elsewhere rates increased. Land use, onshore of where the turtles feed, may play a role. Elevated disease rates were clustered in watersheds with high nitrogen-footprints; an index of natural and anthropogenic factors that affect coastal eutrophication. Further analysis shows strong epidemiological links between disease rates, nitrogen-footprints, and invasive macroalgae and points to foraging ecology. These turtles now forage on invasive macroalgae, which can dominate nutrient rich waters and sequester environmental N in the amino acid arginine. Arginine is known to regulate immune activity, promote herpesviruses, and contribute to tumor formation. Our results have implications for understanding diseases in aquatic organisms, eutrophication, herpesviruses, and tumor formation. PMID:20927370

Effects of Maximal Sodium and Potassium Conductance on the Stability of Hodgkin-Huxley Model

PubMed Central

Wang, Kuanquan; Yuan, Yongfeng; Zhang, Henggui

2014-01-01

Hodgkin-Huxley (HH) equation is the first cell computing model in the world and pioneered the use of model to study electrophysiological problems. The model consists of four differential equations which are based on the experimental data of ion channels. Maximal conductance is an important characteristic of different channels. In this study, mathematical method is used to investigate the importance of maximal sodium conductance g-Na and maximal potassium conductance g-K. Applying stability theory, and taking g-Na and g-K as variables, we analyze the stability and bifurcations of the model. Bifurcations are found when the variables change, and bifurcation points and boundary are also calculated. There is only one bifurcation point when g-Na is the variable, while there are two points when g-K is variable. The (g-Na,  g-K) plane is partitioned into two regions and the upper bifurcation boundary is similar to a line when both g-Na and g-K are variables. Numerical simulations illustrate the validity of the analysis. The results obtained could be helpful in studying relevant diseases caused by maximal conductance anomaly. PMID:25104970

Observation of c.260A > G mutation in superoxide dismutase 1 that causes p.Asn86Ser in Iranian amyotrophic lateral sclerosis patient and absence of genotype/phenotype correlation.

PubMed

Khani, Marzieh; Alavi, Afagh; Nafissi, Shahriar; Elahi, Elahe

2015-07-06

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder in European populations. ALS can be sporadic ALS (SALS) or familial ALS (FALS). Among 20 known ALS genes, mutations in C9orf72 and superoxide dismutase 1 (SOD1) are the most common genetic causes of the disease. Whereas C9orf72 mutations are more common in Western populations, the contribution of SOD1 to ALS in Iran is more than C9orf72. At present, a clear genotype/phenotype correlation for ALS has not been identified. We aimed to perform mutation screening of SOD1 in a newly identified Iranian FALS patient and to assess whether a genotype/phenotype correlation for the identified mutation exists. The five exons of SOD1 and flanking intronic sequences of a FALS proband were screened for mutations by direct sequencing. The clinical features of the proband were assessed by a neuromuscular specialist (SN). The phenotypic presentations were compared to previously reported patients with the same mutation. Heterozygous c.260A > G mutation in SOD1 that causes Asn86Ser was identified in the proband. Age at onset was 34 years and site of the first presentation was in the lower extremities. Comparisons of clinical features of different ALS patients with the same mutation evidenced variable presentations. The c.260A > G mutation in SOD1 that causes Asn86Ser appears to cause ALS with variable clinical presentations.

Type and Timing of Menopause and Later Life Mortality Among Women in the Iowa Established Populations for the Epidemiological Study of the Elderly Cohort

PubMed Central

Cooper, Rachel; Wallace, Robert B.; Guralnik, Jack M.

2012-01-01

Abstract Background The relationship between menopausal characteristics and later life mortality is unclear. We tested the hypotheses that women with surgical menopause would have increased all-cause and cardiovascular mortality compared with women with natural menopause, and that women with earlier ages at natural or surgical menopause would have greater all-cause and cardiovascular mortality than women with later ages at menopause. Methods Women who participated in the Iowa cohort of the Established Populations for the Epidemiologic Study of the Elderly (n=1684) reported menopausal characteristics and potential confounding variables at baseline and were followed up for up to 24 years. Participants were aged 65 years or older at baseline and lived in rural areas. We used survival analysis to examine the relationships between menopausal characteristics and all-cause and cardiovascular mortality. Results A total of 1477 women (87.7% of respondents) died during the study interval. Women with an age at natural menopause ≥55 years had increased all-cause and cardiovascular disease mortality compared with women who had natural menopause at younger ages. Type of menopause and age at surgical menopause were not related to mortality. These patterns persisted after adjustment for potential confounding variables. Conclusions Among an older group of women from a rural area of the United States, later age at natural menopause was related to increased all-cause and cardiovascular mortality. Monitoring the cardiovascular health of this group of older women may contribute to improved survival times. PMID:21970557

MHC class II DRB diversity in raccoons (Procyon lotor) reveals associations with raccoon rabies virus (Lyssavirus).

PubMed

Srithayakumar, Vythegi; Castillo, Sarrah; Rosatte, Rick C; Kyle, Christopher J

2011-02-01

In North America, the raccoon rabies virus (RRV) is an endemic wildlife disease which causes acute encephalopathies and is a strong selective force on raccoons (Procyon lotor), with estimates of ∼85% of the population succumbing to the disease when epizootic. RRV is regarded as a lethal disease if untreated; therefore, no evolutionary response would be expected of raccoon populations. However, variable immune responses to RRV have been observed in raccoons indicating a potential for evolutionary adaptation. Studies of variation within the immunologically important major histocompatibility complex (MHC) have revealed relationships between MHC alleles and diseases in humans and other wildlife species. This enhances our understanding of how hosts and pathogens adapt and co-evolve. In this study, we used RRV as a model system to study host-pathogen interaction in raccoons from a challenge study and from four wild populations that differ in exposure times and viral lineages. We investigated the potential role of Prlo-DRB polymorphism in relation to susceptibility/resistance to RRV in 113 RRV positive and 143 RRV negative raccoons. Six alleles were found to be associated with RRV negative status and five alleles with RRV positive animals. We found variable patterns of MHC associations given the relative number of selective RRV sweeps in the studied regions and correlations between MHC diversity and RRV lineages. The allelic associations established provide insight into how the genetic variation of raccoons may affect the disease outcome and this can be used to examine similar associations between other rabies variants and their hosts.

Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

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

Tan, Min; Schmidt, Robin H.; Beier, Juliane I.

Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a '2-hit' paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% caloriesmore » as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet ({+-} arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: Black-Right-Pointing-Pointer Characterizes a mouse model of arsenic enhanced NAFLD. Black-Right-Pointing-Pointer Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. Black-Right-Pointing-Pointer This effect is associated with increased inflammation.« less

Urine Potassium Excretion, Kidney Failure, and Mortality in CKD.

PubMed

Leonberg-Yoo, Amanda K; Tighiouart, Hocine; Levey, Andrew S; Beck, Gerald J; Sarnak, Mark J

2017-03-01

Low urine potassium excretion, as a surrogate for dietary potassium intake, is associated with higher risk for hypertension and cardiovascular disease in a general population. Few studies have investigated the relationship of urine potassium with clinical outcomes in chronic kidney disease (CKD). Longitudinal cohort study. The MDRD (Modification of Diet in Renal Disease) Study was a randomized controlled trial (N = 840) conducted in 1989 to 1993 to examine the effects of blood pressure control and dietary protein restriction on kidney disease progression in adults aged 18 to 70 years with CKD stages 2 to 4. This post hoc analysis included 812 participants. The primary predictor variable was 24-hour urine potassium excretion, measured at baseline and at multiple time points (presented as time-updated average urine potassium excretion). Kidney failure, defined as initiation of dialysis therapy or transplantation, was determined from US Renal Data System data. All-cause mortality was assessed using the National Death Index. Median follow-up for kidney failure was 6.1 (IQR, 3.5-11.7) years, with 9 events/100 patient-years. Median all-cause mortality follow-up was 19.2 (IQR, 10.8-20.6) years, with 3 deaths/100 patient-years. Baseline mean urine potassium excretion was 2.39±0.89 (SD) g/d. Each 1-SD higher baseline urine potassium level was associated with an adjusted HR of 0.95 (95% CI, 0.87-1.04) for kidney failure and 0.83 (95% CI, 0.74-0.94) for all-cause mortality. Results were consistent using time-updated average urine potassium measurements. Analyses were performed using urine potassium excretion as a surrogate for dietary potassium intake. Results are obtained from a primarily young, nondiabetic, and advanced CKD population and may not be generalizable to the general CKD population. Higher urine potassium excretion was associated with lower risk for all-cause mortality, but not kidney failure. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Systematic age-related differences in chronic disease management in a population-based cohort study: a new paradigm of primary care is required.

PubMed

Buja, Alessandra; Damiani, Gianfranco; Gini, Rosa; Visca, Modesta; Federico, Bruno; Donato, Daniele; Francesconi, Paolo; Marini, Alessandro; Donatini, Andrea; Brugaletta, Salvatore; Baldo, Vincenzo; Donata Bellentani, Maria

2014-01-01

Our interest in chronic conditions is due to the fact that, worldwide, chronic diseases have overtaken infectious diseases as the leading cause of death and disability, so their management represents an important challenge for health systems. The aim of this study was to compare the performance of primary health care services in managing diabetes, congestive heart failure (CHF) and coronary heart disease (CHD), by age group. This population-based retrospective cohort study was conducted in Italy, enrolling 1,948,622 residents ≥ 16 years old. A multilevel regression model was applied to analyze compliance to care processes with explanatory variables at both patient and district level, using age group as an independent variable, and adjusting for sex, citizenship, disease duration, and Charlson index on the first level, and for District Health Unit on the second level. The quality of chronic disease management showed an inverted U-shaped relationship with age. In particular, our findings indicate lower levels for young adults (16-44 year-olds), adults (45-64), and oldest old (+85) than for patients aged 65-74 in almost all quality indicators of CHD, CHF and diabetes management. Young adults (16-44 y), adults (45-64 y), the very old (75-84 y) and the oldest old (+85 y) patients with CHD, CHF and diabetes are less likely than 65-74 year-old patients to be monitored and treated using evidence-based therapies, with the exceptions of echocardiographic monitoring for CHF in young adult patients, and renal monitoring for CHF and diabetes in the very old. Our study shows that more effort is needed to ensure that primary health care systems are sensitive to chronic conditions in the young and in the very elderly.

Variables Associated With Inpatient and Outpatient Resource Utilization Among Medicare Beneficiaries With Nonalcoholic Fatty Liver Disease With or Without Cirrhosis.

PubMed

Sayiner, Mehmet; Otgonsuren, Munkhzul; Cable, Rebecca; Younossi, Issah; Afendy, Mariam; Golabi, Pegah; Henry, Linda; Younossi, Zobair M

2017-03-01

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide with tremendous clinical burden. The economic burden of NAFLD is not well studied. To assess the economic burden of NAFLD. Medicare beneficiaries (January 1, 2010 to December 31, 2010) with NAFLD diagnosis by International Classification of Diseases, Ninth Revision codes in the absence of other liver diseases were selected. Inpatient and outpatient resource utilization parameters were total charges and total provider payments. NAFLD patients with compensated cirrhosis (CC) were compared with decompensated cirrhosis (DC). A total of 976 inpatients and 4742 outpatients with NAFLD were included-87% were white, 36% male, 30% had cardiovascular disease (CVD) or metabolic syndrome conditions, and 12% had cirrhosis. For inpatients, median total hospital charge was $36,289. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($61,151 vs. $33,863 and $18,804 vs. $10,146, P<0.001). Compared with CC, NAFLD patients with DC had higher charges and payments (P<0.02). For outpatients, median total charge was $9,011. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($12,049 vs. $8,830 and $2,586 vs. $1,734, P<0.001). Compared with CC, DC patients had higher total charges ($15,187 vs. $10,379, P=0.04). In multivariate analysis, variables associated with increased inpatient resource utilization were inpatient mortality, DC, and CVD; for outpatients, having CVD, obesity, and hypertension (all P<0.001). NAFLD is associated with significant economic burden to Medicare. Presence of cirrhosis and CVD are associated with increased resource utilization.

Variables Associated With Inpatient and Outpatient Resource Utilization Among Medicare Beneficiaries With Nonalcoholic Fatty Liver Disease With or Without Cirrhosis

PubMed Central

Sayiner, Mehmet; Otgonsuren, Munkhzul; Cable, Rebecca; Younossi, Issah; Afendy, Mariam; Golabi, Pegah; Henry, Linda

2017-01-01

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide with tremendous clinical burden. The economic burden of NAFLD is not well studied. Goal: To assess the economic burden of NAFLD. Study: Medicare beneficiaries (January 1, 2010 to December 31, 2010) with NAFLD diagnosis by International Classification of Diseases, Ninth Revision codes in the absence of other liver diseases were selected. Inpatient and outpatient resource utilization parameters were total charges and total provider payments. NAFLD patients with compensated cirrhosis (CC) were compared with decompensated cirrhosis (DC). Results: A total of 976 inpatients and 4742 outpatients with NAFLD were included—87% were white, 36% male, 30% had cardiovascular disease (CVD) or metabolic syndrome conditions, and 12% had cirrhosis. For inpatients, median total hospital charge was $36,289. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($61,151 vs. $33,863 and $18,804 vs. $10,146, P<0.001). Compared with CC, NAFLD patients with DC had higher charges and payments (P<0.02). For outpatients, median total charge was $9,011. NAFLD patients with cirrhosis had higher charges and payments than noncirrhotic NAFLD patients ($12,049 vs. $8,830 and $2,586 vs. $1,734, P<0.001). Compared with CC, DC patients had higher total charges ($15,187 vs. $10,379, P=0.04). In multivariate analysis, variables associated with increased inpatient resource utilization were inpatient mortality, DC, and CVD; for outpatients, having CVD, obesity, and hypertension (all P<0.001). Conclusions: NAFLD is associated with significant economic burden to Medicare. Presence of cirrhosis and CVD are associated with increased resource utilization. PMID:27332747

Altered Expression of TAP-1 and Major Histocompatibility Complex Class I in Laryngeal Papillomatosis: Correlation of TAP-1 with Disease

PubMed Central

Vambutas, Andrea; Bonagura, Vincent R.; Steinberg, Bettie M.

2000-01-01

Recurrent respiratory papillomatosis (RRP) is an insidious disease caused by human papillomavirus (HPV) infection. It is characterized by a variable clinical course that can include frequent disease recurrence, significant morbidity, and occasional mortality. The mechanisms responsible for the variability in the clinical course and the persistence of latent HPV infection remain unknown. Effective T-cell-mediated clearance of HPV-infected cells may be defective in patients with RRP, leading to recurrent disease and failure to suppress latent HPV reactivation. This study describes the down-regulation of the transporter associated with antigen presentation (TAP-1) and the major histocompatibility complex (MHC) class I protein expression in laryngeal papilloma tissue biopsies and cell culture of primary explants. There was a statistically significant correlation between reduction of TAP-1 expression in biopsy tissues and rapid recurrence of disease. Patients with RRP had less frequent recurrence if their papillomas expressed TAP-1 at levels close to that of normal tissue, compared with those with very low expression of TAP-1, who had frequent recurrence (32 versus 5 weeks to the next surgical intervention). These findings suggest that HPV may evade immune recognition by down-regulating class I MHC cell surface expression via decreased TAP-1 levels. Expression of TAP-1 could be used for prognostic evaluation of disease severity. Gamma interferon was able to restore class I MHC expression at the surfaces of laryngeal papilloma cells in culture. This up-regulation of class I MHC antigen at the cell surface potentially allows the infected cell to become a target for the immune system again. This finding provides some promise for nonsurgical treatment of laryngeal papillomas. PMID:10618282

Natural biological variation of white matter microstructure is accentuated in Huntington's disease.

PubMed

Gregory, Sarah; Crawford, Helen; Seunarine, Kiran; Leavitt, Blair; Durr, Alexandra; Roos, Raymund A C; Scahill, Rachael I; Tabrizi, Sarah J; Rees, Geraint; Langbehn, Douglas; Orth, Michael

2018-04-22

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a CAG-repeat expansion in the Huntingtin gene. Presence of this expansion signifies certainty of disease onset, but only partly explains age at which onset occurs. Genome-wide association studies have shown that naturally occurring genetic variability influences HD pathogenesis and disease onset. Investigating the influence of biological traits in the normal population, such as variability in white matter properties, on HD pathogenesis could provide a complementary approach to understanding disease modification. We have previously shown that while white matter diffusivity patterns in the left sensorimotor network were similar in controls and HD gene-carriers, they were more extreme in the HD group. We hypothesized that the influence of natural variation in diffusivity on effects of HD pathogenesis on white matter is not limited to the sensorimotor network but extends to cognitive, limbic, and visual networks. Using tractography, we investigated 32 bilateral pathways within HD-related networks, including motor, cognitive, and limbic, and examined diffusivity metrics using principal components analysis. We identified three independent patterns of diffusivity common to controls and HD gene-carriers that predicted HD status. The first pattern involved almost all tracts, the second was limited to sensorimotor tracts, and the third encompassed cognitive network tracts. Each diffusivity pattern was associated with network specific performance. The consistency in diffusivity patterns across both groups coupled with their association with disease status and task performance indicates that naturally-occurring patterns of diffusivity can become accentuated in the presence of the HD gene mutation to influence clinical brain function. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Was the appearance of surfactants in air breathing vertebrates ultimately the cause of decompression sickness and autoimmune disease?

PubMed

Arieli, Ran

2015-01-15

All air breathing vertebrates are endowed with pulmonary surfactants, surface-active lipoprotein complexes formed by type II alveolar cells. Surfactants are deposited in clearly defined areas on the luminal aspect of blood vessels, producing hydrophobic spots. Gas nanobubbles measuring 5-100nm form spontaneously on the smooth hydrophobic spot from dissolved gas. Bubbles nucleate and grow at these spots after decompression from high pressure. Proteins with hydrophobic regions circulating in the blood will adhere to the gas phase-plasma interface. Deformation of their secondary and tertiary configuration will present them as foreign molecules or autoantigens. Components of the intact protein which are also present in a deformed protein may be recognized as foreign too. This process is proposed as the trigger for autoimmune diseases. The presence of autoimmune disease in air breathing vertebrates, increased autoimmunity and the elevated risk of decompression sickness with age, as well as variable sensitivity to both diseases, can be matched with the appearance of surfactant spots. Eliminating these spots may provide protection against both diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

CoQ(10) deficiencies and MNGIE: two treatable mitochondrial disorders.

PubMed

Hirano, Michio; Garone, Caterina; Quinzii, Catarina M

2012-05-01

Although causative mutations have been identified for numerous mitochondrial disorders, few disease-modifying treatments are available. Two examples of treatable mitochondrial disorders are coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Here, we describe clinical and molecular features of CoQ(10) deficiencies and MNGIE and explain how understanding their pathomechanisms have led to rationale therapies. Primary CoQ(10) deficiencies, due to mutations in genes required for ubiquinone biosynthesis, and secondary deficiencies, caused by genetic defects not directly related to CoQ(10) biosynthesis, often improve with CoQ(10) supplementation. In vitro and in vivo studies of CoQ(10) deficiencies have revealed biochemical alterations that may account for phenotypic differences among patients and variable responses to therapy. In contrast to the heterogeneous CoQ(10) deficiencies, MNGIE is a single autosomal recessive disease due to mutations in the TYMP gene encoding thymidine phosphorylase (TP). In MNGIE, loss of TP activity causes toxic accumulations of the nucleosides thymidine and deoxyuridine that are incorporated by the mitochondrial pyrimidine salvage pathway and cause deoxynucleoside triphosphate pool imbalances, which, in turn cause mtDNA instability. Allogeneic hematopoetic stem cell transplantation to restore TP activity and eliminate toxic metabolites is a promising therapy for MNGIE. CoQ(10) deficiencies and MNGIE demonstrate the feasibility of treating specific mitochondrial disorders through replacement of deficient metabolites or via elimination of excessive toxic molecules. Studies of CoQ(10) deficiencies and MNGIE illustrate how understanding the pathogenic mechanisms of mitochondrial diseases can lead to meaningful therapies. This article is part of a Special Issue entitled: Biochemistry of Mitochondria, Life and Intervention 2010. Copyright © 2012 Elsevier B.V. All rights reserved.

Incremental prognostic value of kidney function decline over coronary artery disease for cardiovascular event prediction after coronary computed tomography.

PubMed

Bittencourt, Marcio S; Hulten, Edward A; Ghoshhajra, Brian; Abbara, Suhny; Murthy, Venkatesh L; Divakaran, Sanjay; Nasir, Khurram; Gowdak, Luis Henrique W; Riella, Leonardo V; Chiumiento, Marco; Hoffmann, Udo; Di Carli, Marcelo F; Blankstein, Ron

2015-07-01

It is unknown whether mild chronic kidney disease (CKD) is associated with adverse cardiovascular (CV) prognosis after accounting for coronary artery disease (CAD). Here we evaluated the interplay between CKD and CAD in predicting CV death or myocardial infarction (MI) and all-cause death. We included 1541 consecutive patients in the Partners registry (mean age 55 years, 43% female) over 18 years old with no known prior CAD who underwent coronary computed tomography angiography (CCTA). The results of CCTA were categorized as normal, nonobstructive (under half), or obstructive (half and over). Overall, 653 of the patients had no CAD, 583 had nonobstructive CAD, and 305 had obstructive CAD, while 1299 had eGFR over 60 ml/min per 1.73 m(2) and 242 had an eGFR under this value. The presence and severity of CAD was significantly associated with an increased rate of CV death or MI and all-cause death, even after adjustment for age, gender, symptoms, and risk factors. Similarly, reduced eGFR was significantly associated with CV death or MI and all-cause death after similar adjustment. The addition of reduced GFR to a model which included both clinical variables and CCTA findings resulted in significant improvement in the prediction of CV death or MI and all-cause death. Thus, among individuals referred for CCTA to evaluate CAD, renal dysfunction is associated with an increased rate of CV events, mainly driven by an increase in the rate of noncoronary CV events. In this group of patients, both eGFR and the presence and severity of CAD together improve the prediction of future CV events and death.

Ex Vivo Application of Secreted Metabolites Produced by Soil-Inhabiting Bacillus spp. Efficiently Controls Foliar Diseases Caused by Alternaria spp.

PubMed

Ali, Gul Shad; El-Sayed, Ashraf S A; Patel, Jaimin S; Green, Kari B; Ali, Mohammad; Brennan, Mary; Norman, David

2016-01-15

Bacterial biological control agents (BCAs) are largely used as live products to control plant pathogens. However, due to variable environmental and ecological factors, live BCAs usually fail to produce desirable results against foliar pathogens. In this study, we investigated the potential of cell-free culture filtrates of 12 different bacterial BCAs isolated from flower beds for controlling foliar diseases caused by Alternaria spp. In vitro studies showed that culture filtrates from two isolates belonging to Bacillus subtilis and Bacillus amyloliquefaciens displayed strong efficacy and potencies against Alternaria spp. The antimicrobial activity of the culture filtrate of these two biological control agents was effective over a wider range of pH (3.0 to 9.0) and was not affected by autoclaving or proteolysis. Comparative liquid chromatography-mass spectrometry (LC-MS) analyses showed that a complex mixture of cyclic lipopeptides, primarily of the fengycin A and fengycin B families, was significantly higher in these two BCAs than inactive Bacillus spp. Interaction studies with mixtures of culture filtrates of these two species revealed additive activity, suggesting that they produce similar products, which was confirmed by LC-tandem MS analyses. In in planta pre- and postinoculation trials, foliar application of culture filtrates of B. subtilis reduced lesion sizes and lesion frequencies caused by Alternaria alternata by 68 to 81%. Taken together, our studies suggest that instead of live bacteria, culture filtrates of B. subtilis and B. amyloliquefaciens can be applied either individually or in combination for controlling foliar diseases caused by Alternaria species. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Trends in total and cause-specific mortality by marital status among elderly Norwegian men and women

PubMed Central

2011-01-01

Background Previous research has shown large and increasing relative differences in mortality by marital status in several countries, but few studies have considered trends in cause-specific mortality by marital status among elderly people. Methods The author uses discrete-time hazard regression and register data covering the entire Norwegian population to analyze how associations between marital status and several causes of death have changed for men and women of age 75-89 from 1971-2007. Educational level, region of residence and centrality are included as control variables. There are 804 243 deaths during the 11 102 306 person-years of follow-up. Results Relative to married persons, those who are never married, divorced or widowed have significantly higher mortality for most causes of death. The odds of death are highest for divorcees, followed by never married and widowed. Moreover, the excess mortality among the non-married is higher for men than for women, at least in the beginning of the time period. Relative differences in mortality by marital status have increased from 1971-2007. In particular, the excess mortality of the never married women and, to a lesser extent, men has been rising. The widening of the marital status differentials is most pronounced for mortality resulting from circulatory diseases, respiratory diseases (women), other diseases and external deaths (women). Differences in cancer mortality by marital status have been stable over time. Conclusions Those who are married may have lower mortality because of protective effects of marriage or selection of healthy individuals into marriage, and the importance of such mechanisms may have changed over time. However, with the available data it is not possible to identify the mechanisms responsible for the increasing relative differences in mortality by marital status in Norway. PMID:21733170

Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality.

PubMed

Ulmer, Hanno; Kelleher, Cecily; Diem, Günter; Concin, Hans

2004-01-01

To assess the impact of sex-specific patterns in cholesterol levels on all-cause and cardiovascular mortality in the Vorarlberg Health Monitoring and Promotion Programme (VHM&PP). In this study, 67413 men and 82237 women (aged 20-95 years) underwent 454448 standardized examinations, which included measures of blood pressure, height, weight, and fasting samples for cholesterol, triglycerides, gamma-glutamyl transferase (GGT), and glucose in the 15-year period 1985-1999. Relations between these variables and risk of death were analyzed using two approaches of multivariate analyses (Cox proportional hazard and GEE models). Patterns of cholesterol levels showed marked differences between men and women in relation to age and cause of death. The role of high cholesterol in predicting death from coronary heart disease could be confirmed in men of all ages and in women under the age of 50. In men, across the entire age range, although of borderline significance under the age of 50, and in women from the age of 50 onward only, low cholesterol was significantly associated with all-cause mortality, showing significant associations with death through cancer, liver diseases, and mental diseases. Triglycerides > 200 mg/dl had an effect in women 65 years and older but not in men. This large-scale population-based study clearly demonstrates the contrasting patterns of cholesterol level in relation to risk, particularly among those less well studied previously, that is, women of all ages and younger people of both sexes. For the first time, we demonstrate that the low cholesterol effect occurs even among younger respondents, contradicting the previous assessments among cohorts of older people that this is a proxy or marker for frailty occurring with age.

Use of Recombinant Antigens for Sensitive Serodiagnosis of American Tegumentary Leishmaniasis Caused by Different Leishmania Species.

PubMed

Sato, Camila Massae; Sanchez, Maria Carmen Arroyo; Celeste, Beatriz Julieta; Duthie, Malcolm S; Guderian, Jeffrey; Reed, Steven G; de Brito, Maria Edileuza Felinto; Campos, Marliane Batista; de Souza Encarnação, Helia Valeria; Guerra, Jorge; de Mesquita, Tirza Gabrielle Ramos; Pinheiro, Suzana Kanawati; Ramasawmy, Rajendranath; Silveira, Fernando Tobias; de Assis Souza, Marina; Goto, Hiro

2017-02-01

American tegumentary leishmaniasis (ATL) (also known as cutaneous leishmaniasis [CL]) is caused by various species of protozoa of the genus Leishmania The diagnosis is achieved on a clinical, epidemiological, and pathological basis, supported by positive parasitological exams and demonstration of leishmanin delayed-type hypersensitivity. Serological assays are not routinely used in the diagnosis because many are considered to have low sensitivity and the particular Leishmania species causing the disease can lead to variable performance. In the present study, we generated recombinant versions of two highly conserved Leishmania proteins, Leishmania (Viannia) braziliensis-derived Lb8E and Lb6H, and evaluated both in enzyme-linked immunosorbent assays (ELISA). Recombinant Lb6H (rLb6H) had better performance and reacted with 100.0% of the ATL and 89.4% of the VL samples. These reactions with rLb6H were highly specific (98.5%) when compared against those for samples from healthy control individuals. We then assessed rLb6H against sera from ATL patients infected with different species of Leishmania prevalent in Brazil [Leishmania (Leishmania) amazonensis, L (Viannia) braziliensis, and L (V) guyanensis] and samples from patients with other infectious diseases. In analyses of 500 sera, ELISA using rLb6H detected all 219 ATL samples (sensitivity of 100.0%) with an overall specificity of 93.9% (considering healthy individuals and other infectious diseases patients). Only a minority of samples from Chagas disease patients possessed antibodies against rLb6H, and all of these responses were low (with a highest reactivity index of 2.2). Taken together, our data support further evaluation of rLb6H and the potential for its routine use in the serological diagnosis of ATL. Copyright © 2017 Sato et al.

A Novel Mutation in ERCC8 Gene Causing Cockayne Syndrome

PubMed Central

Taghdiri, Maryam; Dastsooz, Hassan; Fardaei, Majid; Mohammadi, Sanaz; Farazi Fard, Mohammad Ali; Faghihi, Mohammad Ali

2017-01-01

Cockayne syndrome (CS) is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Therefore, mutation analysis of genes involved in CS pathogenesis can be helpful to confirm the suspected clinical diagnosis. Here, we report a novel mutation in ERCC8 gene in a 16-year-old boy who suffers from poor weight gain, short stature, microcephaly, intellectual disability, and photosensitivity. The patient was born to consanguineous family with no previous documented disease in his parents. To identify disease-causing mutation in the patient, whole exome sequencing utilizing next-generation sequencing on an Illumina HiSeq 2000 platform was performed. Results revealed a novel homozygote mutation in ERCC8 gene (NM_000082: exon 11, c.1122G>C) in our patient. Another gene (ERCC6), which is also involved in CS did not have any disease-causing mutations in the proband. The new identified mutation was then confirmed by Sanger sequencing in the proband, his parents, and extended family members, confirming co-segregation with the disease. In addition, different bioinformatics programs which included MutationTaster, I-Mutant v2.0, NNSplice, Combined Annotation Dependent Depletion, The PhastCons, Genomic Evolutationary Rate Profiling conservation score, and T-Coffee Multiple Sequence Alignment predicted the pathogenicity of the mutation. Our study identified a rare novel mutation in ERCC8 gene and help to provide accurate genetic counseling and prenatal diagnosis to minimize new affected individuals in this family. PMID:28848724

A novel COL4A3 mutation causes autosomal-recessive Alport syndrome in a large Turkish family.

PubMed

Uzak, Asli Subasioglu; Tokgoz, Bulent; Dundar, Munis; Tekin, Mustafa

2013-03-01

Alport syndrome (AS) is a genetically heterogeneous disorder that is characterized by hematuria, progressive renal failure typically resulting in end-stage renal disease, sensorineural hearing loss, and variable ocular abnormalities. Only 15% of cases with AS are autosomal recessive and are caused by mutations in the COL4A3 or COL4A4 genes, encoding type IV collagen. Clinical data in a large consanguineous family with four affected members were reviewed, and genomic DNA was extracted. For mapping, 15 microsatellite markers flanking COL4A3, COL4A4, and COL4A5 in 16 family members were typed. For mutation screening, all coding exons of COL4A3 were polymerase chain reaction- amplified and Sanger-sequenced from genomic DNA. The disease locus was mapped to chromosome 2q36.3, where COL4A3 and COL4A4 reside. Sanger sequencing revealed a novel mis-sense mutation (c.2T>C; p.M1T) in exon 1 of COL4A3. The identified nucleotide change was not found in 100 healthy ethnicity-matched controls via Sanger sequencing. We present a large consanguineous Turkish family with AS that was found to have a COL4A3 mutation as the cause of the disease. Although the relationship between the various genotypes and phenotypes in AS has not been fully elucidated, detailed clinical and molecular analyses are helpful for providing data to be used in genetic counseling. It is important to identify new mutations to clarify their clinical importance, to assess the prognosis of the disease, and to avoid renal biopsy for final diagnosis.

A Novel Mutation in ERCC8 Gene Causing Cockayne Syndrome.

PubMed

Taghdiri, Maryam; Dastsooz, Hassan; Fardaei, Majid; Mohammadi, Sanaz; Farazi Fard, Mohammad Ali; Faghihi, Mohammad Ali

2017-01-01

Cockayne syndrome (CS) is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Therefore, mutation analysis of genes involved in CS pathogenesis can be helpful to confirm the suspected clinical diagnosis. Here, we report a novel mutation in ERCC8 gene in a 16-year-old boy who suffers from poor weight gain, short stature, microcephaly, intellectual disability, and photosensitivity. The patient was born to consanguineous family with no previous documented disease in his parents. To identify disease-causing mutation in the patient, whole exome sequencing utilizing next-generation sequencing on an Illumina HiSeq 2000 platform was performed. Results revealed a novel homozygote mutation in ERCC8 gene (NM_000082: exon 11, c.1122G>C) in our patient. Another gene ( ERCC6 ), which is also involved in CS did not have any disease-causing mutations in the proband. The new identified mutation was then confirmed by Sanger sequencing in the proband, his parents, and extended family members, confirming co-segregation with the disease. In addition, different bioinformatics programs which included MutationTaster, I-Mutant v2.0, NNSplice, Combined Annotation Dependent Depletion, The PhastCons, Genomic Evolutationary Rate Profiling conservation score, and T-Coffee Multiple Sequence Alignment predicted the pathogenicity of the mutation. Our study identified a rare novel mutation in ERCC8 gene and help to provide accurate genetic counseling and prenatal diagnosis to minimize new affected individuals in this family.

Modelling space of spread Dengue Hemorrhagic Fever (DHF) in Central Java use spatial durbin model

NASA Astrophysics Data System (ADS)

Ispriyanti, Dwi; Prahutama, Alan; Taryono, Arkadina PN

2018-05-01

Dengue Hemorrhagic Fever is one of the major public health problems in Indonesia. From year to year, DHF causes Extraordinary Event in most parts of Indonesia, especially Central Java. Central Java consists of 35 districts or cities where each region is close to each other. Spatial regression is an analysis that suspects the influence of independent variables on the dependent variables with the influences of the region inside. In spatial regression modeling, there are spatial autoregressive model (SAR), spatial error model (SEM) and spatial autoregressive moving average (SARMA). Spatial Durbin model is the development of SAR where the dependent and independent variable have spatial influence. In this research dependent variable used is number of DHF sufferers. The independent variables observed are population density, number of hospitals, residents and health centers, and mean years of schooling. From the multiple regression model test, the variables that significantly affect the spread of DHF disease are the population and mean years of schooling. By using queen contiguity and rook contiguity, the best model produced is the SDM model with queen contiguity because it has the smallest AIC value of 494,12. Factors that generally affect the spread of DHF in Central Java Province are the number of population and the average length of school.

Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.

PubMed

2016-10-08

Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4-19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30-2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35-2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20-30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. Bill & Melinda Gates Foundation. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Predictors of dietary and fluid non-adherence in Jordanian patients with end-stage renal disease receiving haemodialysis: a cross-sectional study.

PubMed

Khalil, Amani A; Darawad, Muhammad; Al Gamal, Eklas; Hamdan-Mansour, Ayman M; Abed, Mona A

2013-01-01

The purpose of this study is to provide insight into the relationship between dietary and fluid non-adherence, depressive symptoms, quality of life, perceived barriers and benefits of exercise, and perceived social support among Jordanian patients with end-stage renal disease receiving haemodialysis using Pender's health promotion model. Non-adherence to dietary and fluid restrictions is a leading cause of treatment failure and poor outcomes in end-stage renal disease. Yet, factors that interfere with the patients' ability to follow their dietary restrictions are unknown. A descriptive, correlational, cross-sectional design was used. Jordanian patients (n = 190) with end-stage renal disease receiving haemodialysis from three main Jordanian cities were included. The dialysis diet and fluid nonadherence questionnaire, Beck Depression Inventory-II, Quality Of Life Index, Dialysis Patient-Perceived Exercise Benefits and Barriers Scale, and the Multidimensional Perceived Social Support were employed to measure the key variables. Patients were more likely men with mean age of 48·2 ± 14·9. Only 27% of the patients showed full commitment to diet guidelines and 23% to fluid guidelines during the last 14 days. Depression (M = 18·8 ± 11·4) had significant negative association with quality of life (importance and satisfaction) (r = -0·60, r = -0·32, p = 0·001, respectively). Multiple hierarchal regressions revealed a predictive model of only two variables: age (B = -0·22, p = 0·05) and residual renal function (B = -0·23, p = 0·012) for dietary non-adherence. Non-adherence to diet and fluid guidelines association with individual characteristics, health perception and psychosocial variables should be investigated in a longitudinal design. Relationship of non-adherence with culture-related factors should deeply be assessed among Jordanian patients with end-stage renal disease receiving haemodialysis. Identification of the factors that may worsen dietary and fluid non-adherence may lead to improved therapeutic interventions within the mainstream of medical practice for Jordanian patients with end-stage renal disease receiving haemodialysis. © 2012 Blackwell Publishing Ltd.

Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study.

PubMed

Häggström, J; Boswood, A; O'Grady, M; Jöns, O; Smith, S; Swift, S; Borgarelli, M; Gavaghan, B; Kresken, J-G; Patteson, M; Åblad, B; Bussadori, C M; Glaus, T; Kovačević, A; Rapp, M; Santilli, R A; Tidholm, A; Eriksson, A; Belanger, M C; Deinert, M; Little, C J L; Kvart, C; French, A; Rønn-Landbo, M; Wess, G; Eggertsdottir, A; Lynne O'Sullivan, M; Schneider, M; Lombard, C W; Dukes-McEwan, J; Willis, R; Louvet, A; DiFruscia, R

2013-01-01

Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. A total of 260 dogs in CHF because of MMVD. A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Three-dimensional ultrasound imaging of the prostate

NASA Astrophysics Data System (ADS)

Fenster, Aaron; Downey, Donal B.

1999-05-01

Ultrasonography, a widely used imaging modality for the diagnosis and staging of many diseases, is an important cost- effective technique, however, technical improvements are necessary to realize its full potential. Two-dimensional viewing of 3D anatomy, using conventional ultrasonography, limits our ability to quantify and visualize most diseases, causing, in part, the reported variability in diagnosis and ultrasound guided therapy and surgery. This occurs because conventional ultrasound images are 2D, yet the anatomy is 3D; hence the diagnostician must integrate multiple images in his mind. This practice is inefficient, and may lead to operator variability and incorrect diagnoses. In addition, the 2D ultrasound image represents a single thin plane at some arbitrary angle in the body. It is difficult to localize and reproduce the image plane subsequently, making conventional ultrasonography unsatisfactory for follow-up studies and for monitoring therapy. Our efforts have focused on overcoming these deficiencies by developing 3D ultrasound imaging techniques that can acquire B-mode, color Doppler and power Doppler images. An inexpensive desktop computer is used to reconstruct the information in 3D, and then is also used for interactive viewing of the 3D images. We have used 3D ultrasound images for the diagnosis of prostate cancer, carotid disease, breast cancer and liver disease and for applications in obstetrics and gynecology. In addition, we have also used 3D ultrasonography for image-guided minimally invasive therapeutic applications of the prostate such as cryotherapy and brachytherapy.

Dilated cardiomyopathy and severe heart failure. An update for pediatricians.

PubMed

Caviedes Bottner, Paola; Córdova Fernández, Tamara; Larraín Valenzuela, Marcos; Cruces Romero Presentación de Casos Clínicos, Pablo

2018-06-01

Dilated cardiomyopathy is the main cause of heart failure leading to heart transplant. Its prognosis is variable and depends on the etiology, the patient's age at onset, and the severity. The management of dilated cardiomyopathy is aimed at minimizing symptoms and preventing disease progression; it requires a comprehensive screening for comorbidities and the prevention of complications to improve the overall status of these children and mitigate their prognosis. Here we present a review oriented at the multidisciplinary management that pediatricians should consider when seeing these patients. Sociedad Argentina de Pediatría.

A novel COL1A1 mutation in a family with osteogenesis imperfecta associated with phenotypic variabilities

PubMed Central

Seto, Toshiyuki; Yamamoto, Toshiyuki; Shimojima, Keiko; Shintaku, Haruo

2017-01-01

Osteogenesis imperfecta (OI) is a heterogeneous disorder that is characterized by bone fragility and systemic complications, and is mainly caused by gene mutations in COL1A1 or COL1A2. A novel COL1A1 splicing mutation, c.750+2T>A, was identified in a Japanese OI family. Only the proband in this family showed various complications, such as heart valve diseases and severe scoliosis. The clinical heterogeneity in the family is discussed in this study. PMID:28326186