Sample records for underlying disease state

  1. 48 CFR 1352.228-70 - Insurance coverage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... applicable Federal and State workers' compensation and occupational disease statutes. If occupational diseases are not compensable under those statutes, they shall be covered under the employer's liability...

  2. Divergent cellular responses during asymptomatic subclinical and clinical states of disease in cows naturally infected with Mycobacterium avium subsp. paratuberculosis

    USDA-ARS?s Scientific Manuscript database

    Infection of the host with Mycobacterium avium subsp. paratuberculosis (MAP) results in a chronic and progressive enteritis that traverses both subclinical and clinical stages. The mechanism(s) for the shift from asymptomatic subclinical disease state to advanced clinical disease are not fully under...

  3. Quantitative characteristics of the foot-and-mouth disease carrier state under natural conditions in India

    USDA-ARS?s Scientific Manuscript database

    The goal of the current study was to characterize serological and virological parameters of the foot-and-mouth disease (FMD) carrier state at two farms in Nainital District, Uttarakhand State in northern India. Despite previous vaccination of cattle in these herds, clinical signs of FMD occurred in ...

  4. Under-reporting of pelvic inflammatory disease in Hawaii: a comparison of state surveillance and hospitalization data.

    PubMed

    Pacheco, Misty; Sentell, Tetine; Katz, Alan R

    2014-04-01

    Hawaii is one of only 19 states for which pelvic inflammatory disease (PID) is a mandated notifiable disease. In order to assess the completeness of PID reporting, we compared the number of hospitalized PID cases in the state of Hawaii with the total number of PID cases reported to the Hawaii State Department of Health surveillance system from 2007 through 2010. While 828 unique PID cases were diagnosed in Hawaii hospitals, only 240 unique PID cases were reported through the state's surveillance system. Severe PID underreporting was seen despite mandatory reporting laws.

  5. A profile of Hawaiians in the Medicaid Fee-For-Service program.

    PubMed

    Loke, M; Kang-Kaulupali, K T; Honbo, L

    2001-09-01

    In Hawai'i, the Medicaid Fee-For-Service (FFS) program enrolled approximately 39,000 individuals in fiscal year (FY) 1999. This program specifically provides healthcare services to enrollees classified as aged, blind, disabled, in-state foster children, and children who live out-of-state in subsidized adoptions. The total expenditure associated with this program was over $300 million in FY 1999. Nearly 4,600 enrollees in the Medicaid FFS program were self-identified as Native Hawaiians or part-Hawaiians. Although the proportion of Hawaiians in the Medicaid program was a fair representation of Hawaiians in the state, the distribution by recipient category within the program was in sharp contrast. Aged Hawaiians appeared to be under-represented in the program while disabled Hawaiians were overrepresented. Foster children and children under subsidized adoption accounted for 1% of the total Hawaiian population. Excluding the foster children and children under subsidized adoption, recipients of Hawaiian ancestry in the Medicaid FFS program (aged, blind, and disabled) obtained health care services amounting to approximately $34 million in FY 1999. Females in this population received more services, with total Medicaid payments amounting to $18.7 million. A higher proportion of Hawaiian recipients were on the neighbor islands. In this FFS Hawaiian population, the top three disease-states by dollar volume in FY 1999, were Alzheimer's disease, acute cerebrovascular disease, and profound mental retardation. A total of $3 million in services were provided to recipients with these primary disease-states. The five leading disease-states facing Hawaiians were generally comparable to those confronting the overall FFS population.

  6. Socio-environmental factors and diarrheal diseases in under five-year old children in the state of Tocantins, Brazil

    PubMed Central

    Graepp-Fontoura, Iolanda; Santos, Floriacy Stabnow; Santos Neto, Marcelino; Tavares, Hanari Santos de Almeida; Bezerra, Maria Onice Lopes; Feitosa, Marcela de Oliveira; Neves, Adriano Figuerêdo; de Morais, Jesuane Cavalcante Melo; Nascimento, Luiz Fernando Costa

    2018-01-01

    Background Diarrhea is a waterborne disease that affects children, especially those under 5 years of age. The objective of this study was to identify the spatial patterns of distribution of diarrheal disease in under 5-year-old children in the State of Tocantins, Brazil, from 2008 to 2013. Methods Geoprocessing tools were used to carry out an epidemiological study, to prepare thematic maps in the TerraView 4.2.2 software based on secondary data. General indicators of the disease, presence of spatial dependence through the Global Moran’s Index (I) and the Spatial Association Index (LISA) were described. Results There were 3,015 cases of under 5-year-old children hospitalized for diarrhea, with an average annual rate (AAR) of 4.10/1,000 inhabitants (inhab.). Among the main characteristics were: increasing rates in under 1-year-old children (6.16 to 9.66/1,000 inhabitants); children aged 1 to 4 full years (63%); males (55%); 8 deaths of under one-year-old children (75%); county of Araguaína (67%); incidence in the county of Nazaré (63.97/1,000 inhab.); prevalence and incidence in the Araguaína microregion (45%, AAR 9.38/1,000 inhab.). The presence of a cluster with spatial autocorrelation was found in the Araguaína microregion, which was statistically significant (I = 0.11, p-value < 0.03), with priority of intervention (Moran Map). Conclusions There was an increase in the number of hospitalizations for diarrhea in under 5–year-old children in the state of Tocantins. The spatial analysis identified clusters of priority areas for measures of maintenance and control of diarrheal diseases. PMID:29768428

  7. State Department of Public Health v. Wells.

    PubMed

    1989-09-07

    The Alabama Court of Civil Appeals decided that under state law the results of an inmate's HIV-AIDS test remain confidential. The release of test results may be done by physicians or state health officers to third parties where the risk of disease transmittal is foreseeable, real, or probable. An inmate awaiting transfer from a county jail to a state prison voluntarily submitted to HIV testing, and the county sheriff sought to compel release of the results. Under the state Notifiable Diseases Act, the county could not compel testing of those inmates awaiting transfer, nor could it compel release of the results of that testing. The results are confidential unless the test is compulsory or the inmate gives written consent, and then the discretion to divulge the results resides in physicians or state health personnel rather than in the courts.

  8. Tremor frequency characteristics in Parkinson's disease under resting-state and stress-state conditions.

    PubMed

    Lee, Hong Ji; Lee, Woong Woo; Kim, Sang Kyong; Park, Hyeyoung; Jeon, Hyo Seon; Kim, Han Byul; Jeon, Beom S; Park, Kwang Suk

    2016-03-15

    Tremor characteristics-amplitude and frequency components-are primary quantitative clinical factors for diagnosis and monitoring of tremors. Few studies have investigated how different patient's conditions affect tremor frequency characteristics in Parkinson's disease (PD). Here, we analyzed tremor characteristics under resting-state and stress-state conditions. Tremor was recorded using an accelerometer on the finger, under resting-state and stress-state (calculation task) conditions, during rest tremor and postural tremor. The changes of peak power, peak frequency, mean frequency, and distribution of power spectral density (PSD) of tremor were evaluated across conditions. Patients whose tremors were considered more than "mild" were selected, for both rest (n=67) and postural (n=25) tremor. Stress resulted in both greater peak powers and higher peak frequencies for rest tremor (p<0.001), but not for postural tremor. Notably, peak frequencies were concentrated around 5 Hz under stress-state condition. The distributions of PSD of tremor were symmetrical, regardless of conditions. Tremor is more evident and typical tremor characteristics, namely a lower frequency as amplitude increases, are different in stressful condition. Patient's conditions directly affect neural oscillations related to tremor frequencies. Therefore, tremor characteristics in PD should be systematically standardized across patient's conditions such as attention and stress levels. Copyright © 2016. Published by Elsevier B.V.

  9. Detecting the tipping points in a three-state model of complex diseases by temporal differential networks.

    PubMed

    Chen, Pei; Li, Yongjun; Liu, Xiaoping; Liu, Rui; Chen, Luonan

    2017-10-26

    The progression of complex diseases, such as diabetes and cancer, is generally a nonlinear process with three stages, i.e., normal state, pre-disease state, and disease state, where the pre-disease state is a critical state or tipping point immediately preceding the disease state. Traditional biomarkers aim to identify a disease state by exploiting the information of differential expressions for the observed molecules, but may fail to detect a pre-disease state because there are generally little significant differences between the normal and pre-disease states. Thus, it is challenging to signal the pre-disease state, which actually implies the disease prediction. In this work, by exploiting the information of differential associations among the observed molecules between the normal and pre-disease states, we propose a temporal differential network based computational method to accurately signal the pre-disease state or predict the occurrence of severe disease. The theoretical foundation of this work is the quantification of the critical state using dynamical network biomarkers. Considering that there is one stationary Markov process before reaching the tipping point, a novel index, inconsistency score (I-score), is proposed to quantitatively measure the change of the stationary processes from the normal state so as to detect the onset of pre-disease state. In other words, a drastic increase of I-score implies the high inconsistency with the preceding stable state and thus signals the upcoming critical transition. This approach is applied to the simulated and real datasets of three diseases, which demonstrates the effectiveness of our method for predicting the deterioration into disease states. Both functional analysis and pathway enrichment also validate the computational results from the perspectives of both molecules and networks. At the molecular network level, this method provides a computational way of unravelling the underlying mechanism of the dynamical progression when a biological system is near the tipping point, and thus detecting the early-warning signal of the imminent critical transition, which may help to achieve timely intervention. Moreover, the rewiring of differential networks effectively extracts discriminatively interpretable features, and systematically demonstrates the dynamical change of a biological system.

  10. 20 CFR 725.535 - Reductions; receipt of State or Federal benefit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... pneumoconiosis under State laws relating to workers' compensation (including compensation for occupational disease), unemployment compensation, or disability insurance. (b) Benefit payments to a beneficiary for...

  11. 7 CFR 319.8 - Notice of quarantine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....), the flag smut disease (Urocystis tritici Koern.), and other injurious plant diseases and insect pests... United States of said plant diseases and insect pests, which are new to or not heretofore widely... specific cases, when the public interests will permit, authorize such importation under conditions...

  12. 7 CFR 319.8 - Notice of quarantine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....), the flag smut disease (Urocystis tritici Koern.), and other injurious plant diseases and insect pests... United States of said plant diseases and insect pests, which are new to or not heretofore widely... specific cases, when the public interests will permit, authorize such importation under conditions...

  13. 7 CFR 319.8 - Notice of quarantine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ....), the flag smut disease (Urocystis tritici Koern.), and other injurious plant diseases and insect pests... United States of said plant diseases and insect pests, which are new to or not heretofore widely... specific cases, when the public interests will permit, authorize such importation under conditions...

  14. A risk assessment of climate change and the impact of forest diseases on forest ecosystems in the Western United States and Canada

    Treesearch

    John T. Kliejunas

    2011-01-01

    This risk assessment projects the effects of eight forest diseases under two climate-change scenarios (warmer and drier, warmer and wetter). Examples are used to describe how various types of forest diseases may respond to environmental changes. Forest diseases discussed in this report include foliar diseases, Phytophthora diseases, stem rusts,...

  15. Wildlife mortality investigation and disease research: contributions of the USGS National Wildlife Health Center to endangered species management and recovery

    USGS Publications Warehouse

    Brand, Christopher J.

    2013-01-01

    The U.S. Geological Survey—National Wildlife Health Center (NWHC) provides diagnostic services, technical assistance, applied research, and training to federal, state, territorial, and local government agencies and Native American tribes on wildlife diseases and wildlife health issues throughout the United States and its territories, commonwealth, and freely associated states. Since 1975, >16,000 carcasses and specimens from vertebrate species listed under the Endangered Species Act have been submitted to NWHC for determination of causes of morbidity or mortality or assessment of health/disease status. Results from diagnostic investigations, analyses of the diagnostic database, technical assistance and consultation, field investigation of epizootics, and wildlife disease research by NWHC wildlife disease specialists have contributed importantly to the management and recovery of listed species.

  16. Wildlife mortality investigation and disease research: contributions of the USGS National Wildlife Health Center to endangered species management and recovery.

    PubMed

    Brand, Christopher J

    2013-12-01

    The U.S. Geological Survey-National Wildlife Health Center (NWHC) provides diagnostic services, technical assistance, applied research, and training to federal, state, territorial, and local government agencies and Native American tribes on wildlife diseases and wildlife health issues throughout the United States and its territories, commonwealth, and freely associated states. Since 1975, >16,000 carcasses and specimens from vertebrate species listed under the Endangered Species Act have been submitted to NWHC for determination of causes of morbidity or mortality or assessment of health/disease status. Results from diagnostic investigations, analyses of the diagnostic database, technical assistance and consultation, field investigation of epizootics, and wildlife disease research by NWHC wildlife disease specialists have contributed importantly to the management and recovery of listed species.

  17. Nonlinear Dynamics, Noise and Cooperative Behavior in Affective Disorders

    NASA Astrophysics Data System (ADS)

    Huber, Martin

    2001-03-01

    Mood disorders tend to be recurrent and progressive and illness patterns typically evolve from isolated episodes at the beginning to more rapid, rhythmic and finally irregular "chaotic" mood patterns. This chararacteristic timecourse prompted the consideration of nonlinear dynamics as a way to describe and analyze course and disease states of mood disorders. Indeed, some evidences now exist indicating that low-dimensional dynamics underly the illness progression. To gain an understanding of prinicple mechanisms that might underly the course and disease patterns of mood disorders, we developed a phenomenological mathematical model for the disease course. In doing so, we made use of a neuronal analogy that exists between disease patterns and neuronal spike patterns and which is commonly referred to as the kindling model of mood disorders (Post, Am J of Psychiatry 1992,149:999-1010; Huber, Braun, Krieg, Biol Psychiatry 1999,46:256-262; Huber, Braun, Krieg, Biol Psychiatry 2000,47:634-642). Using a computational implementation of this approach we investigated the possible relevance of nonlinear dynamics for the disease course, the role of cooperative interactions between nonlinear and noisy dynamics as well as the effect of sensitization mechanisms between disease episodes and disease system. Our simulations show that a low-dimensional model can phenomenologically map the timecourse of mood disorders. From a functional perspective, the model indicates an important role for stochastic fluctuations which can amplify subthreshold states into disease states and can induce transitions to irregular rapidly changing disease patterns. Interesting dynamics are observed with respect to deterministically defined disease states and their dependence on noise intensity. Finally, our simulations show how sensitization effects quite naturally lead to a disease course which ends in irregular fluctuating disease patterns as observed in clinical data. Our findings indicate the usefulness of a computational approach as a way to understand and explain the complexity of temporal disease dynamics of mood disorders but also to procede to new experimental approaches for disease characterisation with the aim of better treatment options.

  18. Automatic detection of retina disease: robustness to image quality and localization of anatomy structure.

    PubMed

    Karnowski, T P; Aykac, D; Giancardo, L; Li, Y; Nichols, T; Tobin, K W; Chaum, E

    2011-01-01

    The automated detection of diabetic retinopathy and other eye diseases in images of the retina has great promise as a low-cost method for broad-based screening. Many systems in the literature which perform automated detection include a quality estimation step and physiological feature detection, including the vascular tree and the optic nerve / macula location. In this work, we study the robustness of an automated disease detection method with respect to the accuracy of the optic nerve location and the quality of the images obtained as judged by a quality estimation algorithm. The detection algorithm features microaneurysm and exudate detection followed by feature extraction on the detected population to describe the overall retina image. Labeled images of retinas ground-truthed to disease states are used to train a supervised learning algorithm to identify the disease state of the retina image and exam set. Under the restrictions of high confidence optic nerve detections and good quality imagery, the system achieves a sensitivity and specificity of 94.8% and 78.7% with area-under-curve of 95.3%. Analysis of the effect of constraining quality and the distinction between mild non-proliferative diabetic retinopathy, normal retina images, and more severe disease states is included.

  19. A disease state fingerprint for evaluation of Alzheimer's disease.

    PubMed

    Mattila, Jussi; Koikkalainen, Juha; Virkki, Arho; Simonsen, Anja; van Gils, Mark; Waldemar, Gunhild; Soininen, Hilkka; Lötjönen, Jyrki

    2011-01-01

    Diagnostic processes of Alzheimer's disease (AD) are evolving. Knowledge about disease-specific biomarkers is constantly increasing and larger volumes of data are being measured from patients. To gain additional benefits from the collected data, a novel statistical modeling and data visualization system is proposed for supporting clinical diagnosis of AD. The proposed system computes an evidence-based estimate of a patient's AD state by comparing his or her heterogeneous neuropsychological, clinical, and biomarker data to previously diagnosed cases. The AD state in this context denotes a patient's degree of similarity to previously diagnosed disease population. A summary of patient data and results of the computation are displayed in a succinct Disease State Fingerprint (DSF) visualization. The visualization clearly discloses how patient data contributes to the AD state, facilitating rapid interpretation of the information. To model the AD state from complex and heterogeneous patient data, a statistical Disease State Index (DSI) method underlying the DSF has been developed. Using baseline data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), the ability of the DSI to model disease progression from elderly healthy controls to AD and its ability to predict conversion from mild cognitive impairment (MCI) to AD were assessed. It was found that the DSI provides well-behaving AD state estimates, corresponding well with the actual diagnoses. For predicting conversion from MCI to AD, the DSI attains performance similar to state-of-the-art reference classifiers. The results suggest that the DSF establishes an effective decision support and data visualization framework for improving AD diagnostics, allowing clinicians to rapidly analyze large quantities of diverse patient data.

  20. District, state or regional veterinary diagnostic laboratories.

    PubMed

    Gosser, H S; Morehouse, L G

    1998-08-01

    The district, regional or state laboratory is the local laboratory to which veterinarian practitioners usually submit samples, and consequently these laboratories are usually the first to observe a suspected disease problem. In most countries, these laboratories are under the jurisdiction of the State or region in which they are located. In the United States of America (USA), most veterinary diagnostic laboratories are State-associated and operate under the aegis of either the State Department of Agriculture or a university. The national laboratory provides reference assistance to the State laboratories. In the USA, the national Laboratory (the National Veterinary Services Laboratories) acts as a consultant to confirm difficult diagnoses and administer performance tests for State-associated laboratories. District, state or regional laboratories need to share information regarding technological advances in diagnostic procedures. This need was met in the USA by the formation of the American Association of Veterinary Laboratory Diagnosticians (AAVLD) in the late 1950s. Another requirement of district, state or regional diagnostic laboratories is a method to confirm quality assurance, which was fulfilled in the USA by an accreditation programme established through the AAVLD. The Accreditation Committee evaluates laboratories (on request) in terms of organisation, personnel, physical facilities and equipment, records, finance and budget. Those laboratories which meet the standards as established in the 'Essential Requirements for Accreditation' are given accreditation status, which indicates that they have the expertise and facilities to perform tests on food-producing animals for shipment in national or international commerce and on companion, laboratory or zoo animals. While confidentiality of test records is most important, it is becoming necessary to release certain types of animal disease test information if a country is to participate in the exportation of animals and animal products. As district, state and regional laboratories operate under many different administrative entities (i.e., universities, State governments and the Federal government), various checks at different administrative levels provide safeguards and reduce the possibility of faulty disease reporting.

  1. Antioxidant enzymes as redox-based biomarkers: a brief review.

    PubMed

    Yang, Hee-Young; Lee, Tae-Hoon

    2015-04-01

    The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease.

  2. The therapeutic use of the relaxation response in stress-related diseases.

    PubMed

    Esch, Tobias; Fricchione, Gregory L; Stefano, George B

    2003-02-01

    The objective of this work was to investigate a possible (therapeutic) connection between the relaxation response (RR) and stress-related diseases. Further, common underlying molecular mechanisms and autoregulatory pathways were examined. For the question of (patho)physiology and significance of RR techniques in the treatment of stress-related diseases, we analyzed peer-reviewed references only. The RR has been shown to be an appropriate and relevant therapeutic tool to counteract several stress-related disease processes and certain health-restrictions, particularly in certain immunological, cardiovascular, and neurodegenerative diseases/mental disorders. Further, common underlying molecular mechanisms may exist that represent a connection between the stress response, pathophysiological findings in stress-related diseases, and physiological changes/autoregulatory pathways described in the RR. Here, constitutive or low-output nitric oxide (NO) production may be involved in a protective or ameliorating context, whereas inducible, high-output NO release may facilitate detrimental disease processes. In mild or early disease states, a high degree of biological and physiological flexibility may still be possible (dynamic balance). Here, the therapeutic use of RR techniques may be considered particularly relevant, and the observable (beneficial) effects may be exerted via activation of constitutive NO pathways. RR techniques, regularly part of professional stress management or mind/body medical settings, represent an important tool to be added to therapeutic strategies dealing with stress-related diseases. Moreover, as part of 'healthy' life-style modifications, they may serve primary (or secondary) prevention. Further studies are necessary to elucidate the complex physiology underlying the RR and its impact upon stress-related disease states.

  3. Sex Differences and Sex Steroids in Lung Health and Disease

    PubMed Central

    Townsend, Elizabeth A.; Miller, Virginia M.

    2012-01-01

    Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span. PMID:22240244

  4. Immunotherapy for Type 1 Diabetes: Why Do Current Protocols Not Halt the Underlying Disease Process?

    PubMed

    Kolb, Hubert; von Herrath, Matthias

    2017-02-07

    T cell-directed immunosuppression only transiently delays the loss of β cell function in recent-onset type 1 diabetes. We argue here that the underlying disease process is carried by innate immune reactivity. Inducing a non-polarized functional state of local innate immunity will support regulatory T cell development and β cell proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. 42 CFR 51b.203 - Who is eligible for a grant under this subpart?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... GRANTS PROJECT GRANTS FOR PREVENTIVE HEALTH SERVICES Grants for Childhood Immunization Programs § 51b.203... political subdivision of a State which has legal responsibility for disease control under the laws of a...

  6. 42 CFR 51b.203 - Who is eligible for a grant under this subpart?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... GRANTS PROJECT GRANTS FOR PREVENTIVE HEALTH SERVICES Grants for Childhood Immunization Programs § 51b.203... political subdivision of a State which has legal responsibility for disease control under the laws of a...

  7. 42 CFR 51b.203 - Who is eligible for a grant under this subpart?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... GRANTS PROJECT GRANTS FOR PREVENTIVE HEALTH SERVICES Grants for Childhood Immunization Programs § 51b.203... political subdivision of a State which has legal responsibility for disease control under the laws of a...

  8. 42 CFR 51b.203 - Who is eligible for a grant under this subpart?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... GRANTS PROJECT GRANTS FOR PREVENTIVE HEALTH SERVICES Grants for Childhood Immunization Programs § 51b.203... political subdivision of a State which has legal responsibility for disease control under the laws of a...

  9. 42 CFR 51b.203 - Who is eligible for a grant under this subpart?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... GRANTS PROJECT GRANTS FOR PREVENTIVE HEALTH SERVICES Grants for Childhood Immunization Programs § 51b.203... political subdivision of a State which has legal responsibility for disease control under the laws of a...

  10. Invasive Blackberry Species in Oregon, USA: Their Identity and Susceptibility to Rust Disease, and Implications for Biological Control

    USDA-ARS?s Scientific Manuscript database

    Two of five species of European blackberry (Rubus fruticosus L. Aggregate) along the West Coast of the United States are invasive, and they are also similar in appearance. Biological control by Phragmidium violaceum, causal agent of a rust disease, was under consideration when rust-diseased blackber...

  11. 8 CFR 232.2 - Examination in the United States of alien applicants for benefits under the immigration laws and...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Sevices, Centers for Disease Control, Atlanta, GA 30333. (iii) If an alien who if found to be mentally... Quarantine, Center for Prevention Services, Centers for Disease Control, Atlanta, GA 30333, the completed... Prevention Services, Centers for Disease Control, Atlanta, GA 30333. (2) Other aliens. The results of the...

  12. 8 CFR 232.2 - Examination in the United States of alien applicants for benefits under the immigration laws and...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Sevices, Centers for Disease Control, Atlanta, GA 30333. (iii) If an alien who if found to be mentally... Quarantine, Center for Prevention Services, Centers for Disease Control, Atlanta, GA 30333, the completed... Prevention Services, Centers for Disease Control, Atlanta, GA 30333. (2) Other aliens. The results of the...

  13. 7 CFR 2.22 - Under Secretary for Marketing and Regulatory Programs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Consultative Group to Eliminate the Use of Child Labor and Forced Labor in Imported Agricultural Products. (2..., control or eradicate foot-and-mouth disease and other foreign animal diseases (21 U.S.C. 113a); (xiii) The... States in control and eradication of plant and animal diseases and pests; (xv) The Federal Noxious Weed...

  14. 7 CFR 2.22 - Under Secretary for Marketing and Regulatory Programs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Consultative Group to Eliminate the Use of Child Labor and Forced Labor in Imported Agricultural Products. (2..., control or eradicate foot-and-mouth disease and other foreign animal diseases (21 U.S.C. 113a); (xiii) The... States in control and eradication of plant and animal diseases and pests; (xv) The Federal Noxious Weed...

  15. 7 CFR 2.22 - Under Secretary for Marketing and Regulatory Programs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Consultative Group to Eliminate the Use of Child Labor and Forced Labor in Imported Agricultural Products. (2..., control or eradicate foot-and-mouth disease and other foreign animal diseases (21 U.S.C. 113a); (xiii) The... States in control and eradication of plant and animal diseases and pests; (xv) The Federal Noxious Weed...

  16. 7 CFR 2.22 - Under Secretary for Marketing and Regulatory Programs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Consultative Group to Eliminate the Use of Child Labor and Forced Labor in Imported Agricultural Products. (2..., control or eradicate foot-and-mouth disease and other foreign animal diseases (21 U.S.C. 113a); (xiii) The... States in control and eradication of plant and animal diseases and pests; (xv) The Federal Noxious Weed...

  17. Endocrine Dysregulation in Anorexia Nervosa Update

    PubMed Central

    2011-01-01

    Context: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. Evidence Acquisition: Findings of this update are based on a PubMed search and the author's knowledge of this field. Evidence Synthesis: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. Conclusions: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. PMID:21976742

  18. Chronic kidney disease risk reduction in a Hispanic population through pharmacist-based disease-state management.

    PubMed

    Leal, Sandra; Soto, Marisa

    2008-04-01

    The purpose of this study was to evaluate the ability of a pharmacist-based disease-state management service to improve the care of indigent, predominately Spanish-speaking patients with diabetes mellitus and common comorbid conditions at high risk for the development of chronic kidney disease (CKD). Patients at high risk for developing CKD who have diabetes at a community health center were placed in a pharmacist-based disease state management service for CKD risk reduction. A residency-trained, bilingual, certified diabetes educator, with a PharmD served as the patient's provider using diagnostic, educational, and therapeutic management services under a medical staff approved collaborative practice agreement. Outcomes were assessed by using national standards of care for disease control and prevention screening. The impact on CKD was shown with a mean A1C decrease of 2% and improvement in the proportion of patients at target goals for blood pressure, A1C, and cholesterol levels and receiving aspirin and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. A pharmacist-based disease-state management service for CKD risk reduction, care of diabetes, and frequently associated comorbid conditions improved compliance with national standards for diabetes care in a high-risk population.

  19. Estimating the Impact of Reducing Under-Nutrition on the Tuberculosis Epidemic in the Central Eastern States of India: A Dynamic Modeling Study.

    PubMed

    Oxlade, Olivia; Huang, Chuan-Chin; Murray, Megan

    2015-01-01

    Tuberculosis (TB) and under-nutrition are widespread in many low and middle-income countries. Momentum to prioritize under-nutrition has been growing at an international level, as demonstrated by the "Scaling Up Nutrition" movement. Low body mass index is an important risk factor for developing TB disease. The objective of this study was to project future trends in TB related outcomes under different scenarios for reducing under-nutrition in the adult population in the Central Eastern states of India. A compartmental TB transmission model stratified by body mass index was parameterized using national and regional data from India. We compared TB related mortality and incidence under several scenarios that represented a range of policies and programs designed to reduce the prevalence of under-nutrition, based on the experience and observed trends in similar countries. The modeled nutrition intervention scenarios brought about reductions in TB incidence and TB related mortality in the Central Eastern Indian states ranging from 43% to 71% and 40% to 68% respectively, relative to the scenario of no nutritional intervention. Modest reductions in under-nutrition averted 4.8 (95% UR 0.5, 17.1) million TB cases and 1.6 (95% UR 0.5, 5.2) million TB related deaths over a period of 20 years of intervention, relative to the scenario of no nutritional intervention. Complete elimination of under-nutrition in the Central Eastern states averted 9.4 (95% UR 1.5, 30.6) million TB cases and 3.2 (95% UR 0.7-, 10.1) million TB related deaths, relative to the scenario of no nutritional intervention. Our study suggests that intervening on under-nutrition could have a substantial impact on TB incidence and mortality in areas with high prevalence of under-nutrition, even if only small gains in under-nutrition can be achieved. Focusing on under-nutrition may be an effective way to reduce both rates of TB and other diseases associated with under-nutrition.

  20. Large-Scale Analysis of Network Bistability for Human Cancers

    PubMed Central

    Shiraishi, Tetsuya; Matsuyama, Shinako; Kitano, Hiroaki

    2010-01-01

    Protein–protein interaction and gene regulatory networks are likely to be locked in a state corresponding to a disease by the behavior of one or more bistable circuits exhibiting switch-like behavior. Sets of genes could be over-expressed or repressed when anomalies due to disease appear, and the circuits responsible for this over- or under-expression might persist for as long as the disease state continues. This paper shows how a large-scale analysis of network bistability for various human cancers can identify genes that can potentially serve as drug targets or diagnosis biomarkers. PMID:20628618

  1. Antioxidant enzymes as redox-based biomarkers: a brief review

    PubMed Central

    Yang, Hee-Young; Lee, Tae-Hoon

    2015-01-01

    The field of redox proteomics focuses to a large extent on analyzing cysteine oxidation in proteins under different experimental conditions and states of diseases. The identification and localization of oxidized cysteines within the cellular milieu is critical for understanding the redox regulation of proteins under physiological and pathophysiological conditions, and it will in turn provide important information that are potentially useful for the development of novel strategies in the treatment and prevention of diseases associated with oxidative stress. Antioxidant enzymes that catalyze oxidation/reduction processes are able to serve as redox biomarkers in various human diseases, and they are key regulators controlling the redox state of functional proteins. Redox regulators with antioxidant properties related to active mediators, cellular organelles, and the surrounding environments are all connected within a network and are involved in diseases related to redox imbalance including cancer, ischemia/reperfusion injury, neurodegenerative diseases, as well as normal aging. In this review, we will briefly look at the selected aspects of oxidative thiol modification in antioxidant enzymes and thiol oxidation in proteins affected by redox control of antioxidant enzymes and their relation to disease. [BMB Reports 2015; 48(4): 200-208] PMID:25560698

  2. Leading causes of child mortality in Brazil, in 1990 and 2015: estimates from the Global Burden of Disease study.

    PubMed

    França, Elisabeth Barboza; Lansky, Sônia; Rego, Maria Albertina Santiago; Malta, Deborah Carvalho; França, Julia Santiago; Teixeira, Renato; Porto, Denise; Almeida, Marcia Furquim de; Souza, Maria de Fatima Marinho de; Szwarcwald, Célia Landman; Mooney, Meghan; Naghavi, Mohsen; Vasconcelos, Ana Maria Nogales

    2017-05-01

    To analyze under-5 mortality rates and leading causes in Brazil and states in 1990 and 2015, using the Global Burden of Disease Study (GBD) 2015 estimates. The main sources of data for all-causes under-5 mortality and live births estimates were the mortality information system, surveys, and censuses. Proportions and rates per 1,000 live births (LB) were calculated for total deaths and leading causes. Estimates of under-5 deaths in Brazil were 191,505 in 1990, and 51,226 in 2015, 90% of which were infant deaths. The rates per 1,000 LB showed a reduction of 67.6% from 1990 to 2015, achieving the proposed target established by the Millennium Development Goals (MDGs). The reduction generally was more than 60% in states, with a faster reduction in the poorest Northeast region. The ratio of the highest and lowest rates in the states decreased from 4.9 in 1990 to 2.3 in 2015, indicating a reduction in socioeconomic regional disparities. Although prematurity showed a 72% reduction, it still remains as the leading cause of death (COD), followed by diarrheal diseases in 1990, and congenital anomalies, birth asphyxia and septicemia neonatal in 2015. Under-5 mortality has decreased over the past 25 years, with reduction of regional disparities. However, pregnancy and childbirth-related causes remain as major causes of death, together with congenital anomalies. Intersectoral and specific public health policies must be continued to improve living conditions and health care in order to achieve further reduction of under-5 mortality rates in Brazil.

  3. Natural killer cells: In health and disease.

    PubMed

    Mandal, Arundhati; Viswanathan, Chandra

    2015-06-01

    Natural killer (NK) cells constitute our bodies' frontline defense system, guarding against tumors and launching attacks against infections. The activities of NK cells are regulated by the interaction of various receptors expressed on their surfaces with cell surface ligands. While the role of NK cells in controlling tumor activity is relatively clear, the fact that they are also linked to various other disease conditions is now being highlighted. Here, we present an overview of the role of NK cells during normal body state as well as under diseased state. We discuss the possible utilization of these powerful cells as immunotherapeutic agents in combating diseases such as asthma, autoimmune diseases, and HIV-AIDS. This review also outlines current challenges in NK cell therapy. Copyright © 2015. Published by Elsevier B.V.

  4. Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort.

    PubMed

    Setiawan, Veronica Wendy; Stram, Daniel O; Porcel, Jacqueline; Lu, Shelly C; Le Marchand, Loïc; Noureddin, Mazen

    2016-12-01

    Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. CLD and cirrhosis cases were identified using Medicare claims between 1999 and 2012 among the fee-for-service participants (n = 106,458). We used International Classification of Diseases Ninth Revision codes, body mass index, history of diabetes mellitus, and alcohol consumption from questionnaires to identify underlying etiologies. A total of 5,783 CLD (3,575 CLD without cirrhosis and 2,208 cirrhosis) cases were identified. The prevalence of CLD ranged from 3.9% in African Americans and Native Hawaiians to 4.1% in whites, 6.7% in Latinos, and 6.9% in Japanese. Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52%), followed by alcoholic liver disease (21%). NAFLD was the most common cause of cirrhosis in the entire cohort. By ethnicity, NAFLD was the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32% of cases. Alcoholic liver disease was the most common cause of cirrhosis in whites (38.2%), while hepatitis C virus was the most common cause in African Americans (29.8%). We showed racial/ethnic variations in the prevalence of CLD and cirrhosis by underlying etiology; NAFLD was the most common cause of CLD and cirrhosis in the entire cohort, and the high prevalence of NAFLD among Japanese Americans and Native Hawaiians is a novel finding, warranting further studies to elucidate the causes. (Hepatology 2016;64:1969-1977). © 2016 by the American Association for the Study of Liver Diseases.

  5. Anaemia of Chronic Disease: An In-Depth Review.

    PubMed

    Madu, Anazoeze Jude; Ughasoro, Maduka Donatus

    2017-01-01

    Anaemia is the most common haematological disorder affecting humanity and is usually observed in chronic disease states such as non-specific anaemia, which may cause diagnostic difficulties. In chronically ill patients with anaemia, this has a negative impact on quality of life as well as survival. This paper aims at reviewing the pathogenesis of this form of anaemia with a view to suggesting future targets for therapeutic intervention. The ability to diagnose this disorder depends on the ability of the physician to correlate the possible clinical pathways of the underlying disease with the patients' ferrokinetic state. It is important to rule out iron deficiency and other causes of anaemia as misdiagnosis will in most cases lead to refractoriness to standard therapy. The cytokines and acute-phase proteins play important roles in the pathogenesis of anaemia of chronic disease. Alterations in the metabolism of iron via the molecule hepcidin and ferritin are largely responsible for the consequent anaemia. Concomitant iron deficiency might be present and could affect the diagnosis and therapeutic protocol. Treatment options involve the use of erythropoiesis-stimulating agents, blood transfusion, and iron supplementation, in addition to treating the underlying disease. © 2016 S. Karger AG, Basel.

  6. Recurrent pyoderma and its underlying primary diseases: a retrospective evaluation of 157 dogs.

    PubMed

    Seckerdieck, Florian; Mueller, Ralf S

    2018-04-14

    Bacterial pyoderma is common in small animal practice. Usually there is an associated underlying disease, but little is known about the prevalence of underlying diseases in dogs with recurrent pyoderma. The aim of this study was to analyse the frequency of the different underlying diseases in dogs with recurrent pyoderma. In total, 157 animals with recurrent pyoderma were identified in hospital records from 2008 to 2013 and the data analysed for primary diseases. The time between recurrences, the type of clinical signs and the age at pyoderma onset were also evaluated. At least one primary disease was found in 107 dogs. Allergies were the primary cause in 63 dogs, environmental allergy was the most frequent (n=45) and was often associated with other allergies, followed by hypothyroidism (n=12) and hyperadrenocorticism (n=6). Sixteen dogs with recurrent pyoderma suffered from demodicosis. In young dogs with recurrent pyoderma an allergy work-up combined with deep skin scrapings should lead to a diagnosis of the underlying disease in most of the cases. In dogs in which pyoderma began in middle or old age, hormonal testing and ruling out a possible flea infestation should be the first steps. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. First report of leaf rust of blueberry caused by Thekopsora minima in Mexico

    USDA-ARS?s Scientific Manuscript database

    Blueberry (Vaccinium corymbosum L.) is becoming an important crop in the states of Jalisco and Michoacan in Mexico. As the area under blueberry cultivation increases, new diseases causing severe losses are appearing. Leaf rust is one of the most destructive diseases of blueberry in Mexico. Sori on t...

  8. Significantly reduced health burden from ambient air pollution in the United States under emission reductions from 1990 to 2010

    EPA Science Inventory

    The 2015 Global Burden of Disease (GBD) study has listed air pollution as the fourth-ranking global mortality risk factor. Many studies have estimated the global or national burden of disease attributed to air pollution. However, little effort has been focused on understanding ho...

  9. 13 CFR 120.311 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... which: (1) Is organized under federal or state law to operate in the interest of disabled individuals..., mental or emotional impairment, defect, ailment, disease or disability which limits the type of...

  10. 13 CFR 120.311 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... which: (1) Is organized under federal or state law to operate in the interest of disabled individuals..., mental or emotional impairment, defect, ailment, disease or disability which limits the type of...

  11. 13 CFR 120.311 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... which: (1) Is organized under federal or state law to operate in the interest of disabled individuals..., mental or emotional impairment, defect, ailment, disease or disability which limits the type of...

  12. 13 CFR 120.311 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... which: (1) Is organized under federal or state law to operate in the interest of disabled individuals..., mental or emotional impairment, defect, ailment, disease or disability which limits the type of...

  13. Invasion of two tick-borne diseases across New England: harnessing human surveillance data to capture underlying ecological invasion processes

    PubMed Central

    Walter, Katharine S.; Pepin, Kim M.; Webb, Colleen T.; Gaff, Holly D.; Krause, Peter J.; Pitzer, Virginia E.; Diuk-Wasser, Maria A.

    2016-01-01

    Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach—occupancy modelling—to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease. PMID:27252022

  14. Quality indicators for the detection and management of chronic kidney disease in primary care in Canada derived from a modified Delphi panel approach.

    PubMed

    Tu, Karen; Bevan, Lindsay; Hunter, Katie; Rogers, Jess; Young, Jacqueline; Nesrallah, Gihad

    2017-01-01

    The detection and management of chronic kidney disease lies within primary care; however, performance measures applicable in the Canadian context are lacking. We sought to develop a set of primary care quality indicators for chronic kidney disease in the Canadian setting and to assess the current state of the disease's detection and management in primary care. We used a modified Delphi panel approach, involving 20 panel members from across Canada (10 family physicians, 7 nephrologists, 1 patient, 1 primary care nurse and 1 pharmacist). Indicators identified from peer-reviewed and grey literature sources were subjected to 3 rounds of voting to develop a set of quality indicators for the detection and management of chronic kidney disease in the primary care setting. The final indicators were applied to primary care electronic medical records in the Electronic Medical Record Administrative data Linked Database (EMRALD) to assess the current state of primary care detection and management of chronic kidney disease in Ontario. Seventeen indicators made up the final list, with 1 under the category Prevalence, Incidence and Mortality; 4 under Screening, Diagnosis and Risk Factors; 11 under Management; and 1 under Referral to a Specialist. In a sample of 139 993 adult patients not on dialysis, 6848 (4.9%) had stage 3 or higher chronic kidney disease, with the average age of patients being 76.1 years (standard deviation [SD] 11.0); 62.9% of patients were female. Diagnosis and screening for chronic kidney disease were poorly performed. Only 27.1% of patients with stage 3 or higher disease had their diagnosis documented in their cumulative patient profile. Albumin-creatinine ratio testing was only performed for 16.3% of patients with a low estimated glomerular filtration rate (eGFR) and for 28.5% of patients with risk factors for chronic kidney disease. Family physicians performed relatively better with the management of chronic kidney disease, with 90.4% of patients with stage 3 or higher disease having an eGFR performed in the previous 18 months and 83.1% having a blood pressure recorded in the previous 9 months. We propose a set of measurable indicators to evaluate the quality of the management of chronic kidney disease in primary care. These indicators may be used to identify opportunities to improve current practice in Canada.

  15. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease.

    PubMed

    Collins, Allan J; Foley, Robert N; Gilbertson, David T; Chen, Shu-Cheng

    2015-06-01

    The United States Renal Data System (USRDS) began in 1989 through US Congressional authorization under National Institutes of Health competitive contracting. Its history includes five contract periods, two of 5 years, two of 7.5 years, and the fifth, awarded in February 2014, of 5 years. Over these 25 years, USRDS reporting transitioned from basic incidence and prevalence of end-stage renal disease (ESRD), modalities, and overall survival, as well as focused special studies on dialysis, in the first two contract periods to a comprehensive assessment of aspects of care that affect morbidity and mortality in the second two periods. Beginning in 1999, the Minneapolis Medical Research Foundation investigative team transformed the USRDS into a total care reporting system including disease severity, hospitalizations, pediatric populations, prescription drug use, and chronic kidney disease and the transition to ESRD. Areas of focus included issues related to death rates in the first 4 months of treatment, sudden cardiac death, ischemic and valvular heart disease, congestive heart failure, atrial fibrillation, and infectious complications (particularly related to dialysis catheters) in hemodialysis and peritoneal dialysis patients; the burden of congestive heart failure and infectious complications in pediatric dialysis and transplant populations; and morbidity and access to care. The team documented a plateau and decline in incidence rates, a 28% decline in death rates since 2001, and changes under the 2011 Prospective Payment System with expanded bundled payments for each dialysis treatment. The team reported on Bayesian methods to calculate mortality ratios, which reduce the challenges of traditional methods, and introduced objectives under the Health People 2010 and 2020 national health care goals for kidney disease.

  16. Pediatric Invasive Pneumococcal Disease in the United States in the Era of Pneumococcal Conjugate Vaccines

    PubMed Central

    2012-01-01

    Summary: Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae. The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development. PMID:22763632

  17. Solid-support Electron Paramagnetic Resonance (EPR) Studies of Aβ40 Monomers Reveal a Structured State with Three Ordered Segments*

    PubMed Central

    Gu, Lei; Ngo, Sam; Guo, Zhefeng

    2012-01-01

    Alzheimer disease is associated with the pathological accumulation of amyloid-β peptide (Aβ) in the brain. Soluble Aβ oligomers formed during early aggregation process are believed to be neurotoxins and causative agents in Alzheimer disease. Aβ monomer is the building block for amyloid assemblies. A comprehensive understanding of the structural features of Aβ monomer is crucial for delineating the mechanism of Aβ oligomerization. Here we investigated the structures of Aβ40 monomer using a solid-support approach, in which Aβ40 monomers are tethered on the solid support via an N-terminal His tag to prevent further aggregation. EPR spectra of tethered Aβ40 with spin labels at 18 different positions show that Aβ40 monomers adopt a completely disordered structure under denaturing conditions. Under native conditions, however, EPR spectra suggest that Aβ40 monomers adopt both a disordered state and a structured state. The structured state of Aβ40 monomer has three more ordered segments at 14–18, 29–30, and 38–40. Interactions between these segments may stabilize the structured state, which likely plays an important role in Aβ aggregation. PMID:22277652

  18. Epidemic spreading on evolving signed networks

    NASA Astrophysics Data System (ADS)

    Saeedian, M.; Azimi-Tafreshi, N.; Jafari, G. R.; Kertesz, J.

    2017-02-01

    Most studies of disease spreading consider the underlying social network as obtained without the contagion, though epidemic influences people's willingness to contact others: A "friendly" contact may be turned to "unfriendly" to avoid infection. We study the susceptible-infected disease-spreading model on signed networks, in which each edge is associated with a positive or negative sign representing the friendly or unfriendly relation between its end nodes. In a signed network, according to Heider's theory, edge signs evolve such that finally a state of structural balance is achieved, corresponding to no frustration in physics terms. However, the danger of infection affects the evolution of its edge signs. To describe the coupled problem of the sign evolution and disease spreading, we generalize the notion of structural balance by taking into account the state of the nodes. We introduce an energy function and carry out Monte Carlo simulations on complete networks to test the energy landscape, where we find local minima corresponding to the so-called jammed states. We study the effect of the ratio of initial friendly to unfriendly connections on the propagation of disease. The steady state can be balanced or a jammed state such that a coexistence occurs between susceptible and infected nodes in the system.

  19. Diagnosis of equine monocytic ehrlichiosis (Potomac horse fever) by indirect immunofluorescence.

    PubMed

    Ristic, M; Holland, C J; Dawson, J E; Sessions, J; Palmer, J

    1986-07-01

    The recent establishment of a system for the continuous in vitro propagation of Ehrlichia risticii, the causative agent of equine monocytic ehrlichiosis (EME; synonym, Potomac horse fever), has facilitated the development of an indirect fluorescent antibody test for the diagnosis of this disease under laboratory and field conditions. The field diagnostic application of the test has aided in the recognition of the disease in 16 states of the United States and in 1 province of Canada. A limited epidemiologic study conducted between January and September 1985, in an area where the disease is known to be enzootic, revealed that conversion from seronegative to seropositive status is not always accompanied by clinical manifestations of the disease. Confirmatory findings in experimentally inoculated horses suggest the existence of clinically undetectable infections.

  20. Factors Underlying the Temporal Increase in Maternal Mortality in the United States

    PubMed Central

    Joseph, K.S.; Lisonkova, Sarka; Muraca, Giulia M.; Razaz, Neda; Sabr, Yasser; Mehrabadi, Azar; Schisterman, Enrique F.

    2016-01-01

    OBJECTIVE To identify the factors underlying the recent increase in maternal mortality ratios (maternal deaths per 100,000 live births) in the United States. METHODS We carried out a retrospective study with data on maternal deaths and live births in the United States from 1993 to 2014 obtained from the birth and death files of the Centers for Disease Control and Prevention. Underlying causes of death were examined between 1999 and 2014 using International Classification of Diseases, Tenth Revision (ICD-10) codes. Poisson regression was used to estimate maternal mortality rate ratios (RR) and 95% confidence intervals (CI) after adjusting for the introduction of a separate pregnancy question and the standard pregnancy checkbox on death certificates, and adoption of ICD-10. RESULTS Maternal mortality ratios increased from 7.55 in 1993, to 9.88 in 1999 and to 21.5 per 100,000 live births in 2014 (RR 2014 vs 1993 2.84, 95% CI 2.49 to 3.24; RR 2014 vs 1999 2.17, 95% CI 1.93 to 2.45). The increase in maternal deaths from 1999 to 2014 was mainly due to increases in maternal deaths associated with two new ICD-10 codes (O26.8 i.e., primarily renal disease and O99 i.e., other maternal diseases classifiable elsewhere); exclusion of such deaths abolished the increase in mortality (RR 1.09, 95% CI 0.94 to 1.27). Regression adjustment for improvements in surveillance also abolished the temporal increase in maternal mortality ratios (adjusted maternal mortality ratios 7.55 in 1993, 8.00 per 100,000 live births in 2013; adjusted RR 2013 vs 1993 1.06, 95% CI 0.90 to 1.25). CONCLUSION Recent increases in maternal mortality ratios in the United States are likely an artifact of improvements in surveillance and highlight past underestimation of maternal death. Complete ascertainment of maternal death in populations remains a challenge even in countries with good systems for civil registration and vital statistics. PMID:27926651

  1. State-of-the-Art Fluorescence Fluctuation-Based Spectroscopic Techniques for the Study of Protein Aggregation

    PubMed Central

    Kinjo, Masataka

    2018-01-01

    Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are devastating proteinopathies with misfolded protein aggregates accumulating in neuronal cells. Inclusion bodies of protein aggregates are frequently observed in the neuronal cells of patients. Investigation of the underlying causes of neurodegeneration requires the establishment and selection of appropriate methodologies for detailed investigation of the state and conformation of protein aggregates. In the current review, we present an overview of the principles and application of several methodologies used for the elucidation of protein aggregation, specifically ones based on determination of fluctuations of fluorescence. The discussed methods include fluorescence correlation spectroscopy (FCS), imaging FCS, image correlation spectroscopy (ICS), photobleaching ICS (pbICS), number and brightness (N&B) analysis, super-resolution optical fluctuation imaging (SOFI), and transient state (TRAST) monitoring spectroscopy. Some of these methodologies are classical protein aggregation analyses, while others are not yet widely used. Collectively, the methods presented here should help the future development of research not only into protein aggregation but also neurodegenerative diseases. PMID:29570669

  2.  Rapid identification system of frontal dysfunction in subclinical hepatic encephalopathy.

    PubMed

    Moretti, Rita; Gazzin, Silvia; Crocè, Lory Saveria; Baso, Beatrice; Masutti, Flora; Bedogni, Giorgio; Tiribelli, Claudio

    2016-01-01

     Introduction and aim. Liver disease is associated with cognitive dysfunction also at early stages, and minimal hepatic encephalopathy, affecting 20-70% of patients, is frequently under-recognized. The main purpose of this work was to demonstrate that a substantial number of patients, enrolled due to an acute confusional state in absence of a diagnosis of liver disease, suffers of hepatic encephalopathy. Before a diagnosis of a well-compensated liver diseases was performed, 410 patients with an acute confusional state were enrolled in this study. Even in the presence of minimal alterations of hepatic function, the psychometric tests applied demonstrated early signs of cerebral frontal alteration. The alteration was associated with the severity of liver disease, paralleling the progression of the patient to minimal hepatic failure or chronic liver disease. These psychometric tests are essential to detect early and subclinical frontal failure. Frontal dysfunction may be a useful tool in the follow-up of these patients.

  3. Epidemiology of Infectious Disease-Related Death After Release from Prison, Washington State, United States, and Queensland, Australia: A Cohort Study.

    PubMed

    Binswanger, Ingrid A; Blatchford, Patrick J; Forsyth, Simon J; Stern, Marc F; Kinner, Stuart A

    2016-01-01

    People in prison may be at high risk for infectious diseases and have an elevated risk of death immediately after release compared with later; their risk of death is elevated for at least a decade after release. We compared rates, characteristics, and prison-related risk factors for infectious disease-related mortality among people released from prisons in Queensland, Australia, and Washington State, United States, regions with analogous available data. We analyzed data from retrospective cohort studies of people released from prison in Queensland (1997-2007, n=37,180) and Washington State (1999-2009, n=76,208) and linked identifiers from each cohort to its respective national death index. We estimated infectious disease-related mortality rates (deaths per person-years in community) and examined associations using Cox proportional hazard models. The most frequent infectious disease-related underlying cause of death after release from prison was pneumonia (43%, 23/54 deaths) in the Australian cohort and viral hepatitis (40%, 69/171 deaths) in the U.S. cohort. The infectious disease-related mortality rate was significantly higher in the U.S. cohort than in the Australian cohort (51.2 vs. 26.5 deaths per 100,000 person-years; incidence rate ratio = 1.93, 95% confidence interval 1.42, 2.62). In both cohorts, increasing age was strongly associated with mortality from infectious diseases. Differences in the epidemiology of infectious disease-related mortality among people released from prison may reflect differences in patterns of community health service delivery in each region. These findings highlight the importance of preventing and treating hepatitis C and other infectious diseases during the transition from prison to the community.

  4. 8 CFR 253.1 - Parole.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., tuberculosis in any form, leprosy, or any dangerous contagious disease, or an alien crewman suspected of being... strictly in the public interest be paroled into the United States under the provisions of section 212(d)(5...

  5. Valley Fever (Coccidioidomycosis) Statistics

    MedlinePlus

    ... Valley fever may be under-recognized. 2 , 3 Public health surveillance for Valley fever Valley fever is reportable ... MMWR) . Check with your local, state, or territorial public health department for more information about disease reporting requirements ...

  6. Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

    PubMed

    Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

    2017-12-15

    Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

  7. Effects of disease severity and medication state on postural control asymmetry during challenging postural tasks in individuals with Parkinson's disease.

    PubMed

    Barbieri, Fabio A; Polastri, Paula F; Baptista, André M; Lirani-Silva, Ellen; Simieli, Lucas; Orcioli-Silva, Diego; Beretta, Victor S; Gobbi, Lilian T B

    2016-04-01

    The aim of this study was to investigate the effects of disease severity and medication state on postural control asymmetry during challenging tasks in individuals with Parkinson's disease (PD). Nineteen people with PD and 11 neurologically healthy individuals performed three standing task conditions: bipedal standing, tandem and unipedal adapted standing; the individuals with PD performed the tasks in ON and OFF medication state. The participants with PD were distributed into 2 groups according to disease severity: unilateral group (n=8) and bilateral group (n=11). The two PD groups performed the evaluations both under and without the medication. Two force plates were used to analyze the posture. The symmetric index was calculated for various of center of pressure. ANOVA one-way (groups) and two-way (PD groups×medication), with repeated measures for medication, were calculated. For main effects of group, the bilateral group was more asymmetric than CG. For main effects of medication, only unipedal adapted standing presented effects of PD medication. There was PD groups×medication interaction. Under the effects of medication, the unilateral group presented lower asymmetry of RMS in anterior-posterior direction and area than the bilateral group in unipedal adapted standing. In addition, the unilateral group presented lower asymmetry of mean velocity, RMS in anterior-posterior direction and area in unipedal standing and area in tandem adapted standing after a medication dose. Postural control asymmetry during challenging postural tasks was dependent on disease severity and medication state in people with PD. The bilateral group presented higher postural control asymmetry than the control and unilateral groups in challenging postural tasks. Finally, the medication dose was able to reduce postural control asymmetry in the unilateral group during challenging postural tasks. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Exercise training and cardiometabolic diseases: focus on the vascular system.

    PubMed

    Roque, Fernanda R; Hernanz, Raquel; Salaices, Mercedes; Briones, Ana M

    2013-06-01

    The regular practice of physical activity is a well-recommended strategy for the prevention and treatment of several cardiovascular and metabolic diseases. Physical exercise prevents the progression of vascular diseases and reduces cardiovascular morbidity and mortality. Exercise training also ameliorates vascular changes including endothelial dysfunction and arterial remodeling and stiffness, usually present in type 2 diabetes, obesity, hypertension and metabolic syndrome. Common to these diseases is excessive oxidative stress, which plays an important role in the processes underlying vascular changes. At the vascular level, exercise training improves the redox state and consequently NO availability. Moreover, growing evidence indicates that other mediators such as prostanoids might be involved in the beneficial effects of exercise. The purpose of this review is to update recent findings describing the adaptation response induced by exercise in cardiovascular and metabolic diseases, focusing more specifically on the beneficial effects of exercise in the vasculature and the underlying mechanisms.

  9. Plasmacytoid leukemia of chinook salmon.

    PubMed

    Kent, M L; Eaton, W D; Casey, J W

    1997-04-01

    Plasmacytoid leukemia is a common disease of seawater pen-reared chinook salmon (Oncorhynchus tshawytscha) in British Columbia, Canada, but has also been detected in wild salmon, in freshwater-reared salmon in United States, and in salmon from netpens in Chile. The disease can be transmitted under laboratory conditions, and is associated with a retrovirus, the salmon leukemia virus. However, the proliferating plasmablasts are often infected with the microsporean Enterocytozoon salmonis, which may be an important co-factor in the disease.

  10. Traumatic Brain Injury and Personality Change

    ERIC Educational Resources Information Center

    Fowler, Marc; McCabe, Paul C.

    2011-01-01

    Traumatic brain injury (TBI) is the leading cause of death and lifelong disability in the United States for individuals below the age of 45. Current estimates from the Center for Disease Control (CDC) indicate that at least 1.4 million Americans sustain a TBI annually. TBI affects 475,000 children under age 14 each year in the United States alone.…

  11. 42 CFR 413.82 - Direct GME payments: Special rules for States that formerly had a waiver from Medicare...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... formerly had a waiver from Medicare reimbursement principles. 413.82 Section 413.82 Public Health CENTERS... OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL... of a State reimbursement control system under section 1886(c) of the Act, section 402 of the Social...

  12. 42 CFR 413.82 - Direct GME payments: Special rules for States that formerly had a waiver from Medicare...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... formerly had a waiver from Medicare reimbursement principles. 413.82 Section 413.82 Public Health CENTERS... OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL... of a State reimbursement control system under section 1886(c) of the Act, section 402 of the Social...

  13. 42 CFR 413.82 - Direct GME payments: Special rules for States that formerly had a waiver from Medicare...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... formerly had a waiver from Medicare reimbursement principles. 413.82 Section 413.82 Public Health CENTERS... OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL... of a State reimbursement control system under section 1886(c) of the Act, section 402 of the Social...

  14. 42 CFR 413.82 - Direct GME payments: Special rules for States that formerly had a waiver from Medicare...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... formerly had a waiver from Medicare reimbursement principles. 413.82 Section 413.82 Public Health CENTERS... OF REASONABLE COST REIMBURSEMENT; PAYMENT FOR END-STAGE RENAL DISEASE SERVICES; OPTIONAL... of a State reimbursement control system under section 1886(c) of the Act, section 402 of the Social...

  15. Significantly Reduced Health Burden from Ambient Air Pollution in the United States under Emission Reductions from 1990 to 2016

    EPA Science Inventory

    The 2015 Global Burden of Disease (GBD) study has listed air pollution as the fourth-ranking global mortality risk factor. Few studies have attempted to understand how these burdens change through time, especially in the United States (US). Here we aim to estimate air pollution-r...

  16. A current and historical perspective on disparities in US childhood pneumococcal conjugate vaccine adherence and in rates of invasive pneumococcal disease: Considerations for the routinely-recommended, pediatric PCV dosing schedule in the United States

    PubMed Central

    McLaughlin, John M; Utt, Eric A; Hill, Nina M; Welch, Verna L; Power, Edward; Sylvester, Gregg C

    2016-01-01

    Previous research has suggested that reducing the US 4-dose PCV13 schedule to a 3-dose schedule may provide cost savings, despite more childhood pneumococcal disease. The study also stressed that dose reduction should be coupled with improved PCV adherence, however, US PCV uptake has leveled-off since 2008. An estimated 24–36% of US children aged 5–19 months are already receiving a reduced PCV schedule (i.e., missing ≥1 dose). This raises a practical concern that, under a reduced, 3-dose schedule, a similar proportion of children may receive ≤2 doses. It is also unknown if a reduced, 3-dose PCV schedule in the United States will afford the same disease protection as 3-dose schedules used elsewhere, given lower US PCV adherence. Finally, more assurance is needed that, under a reduced schedule, racial, socioeconomic, and geographic disparities in PCV adherence will not correspond with disproportionately higher rates of pneumococcal disease among poor or minority children. PMID:26376039

  17. Is Multiple Sclerosis an Autoimmune Disease?

    PubMed Central

    Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses

    2012-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID:22666554

  18. Defining and characterizing the critical transition state prior to the type 2 diabetes disease

    PubMed Central

    Zhu, Chunqing; Zhou, Xin; Chen, Pei; Fu, Tianyun; Hu, Zhongkai; Wu, Qian; Liu, Wei; Liu, Daowei; Yu, Yunxian; Zhang, Yan; McElhinney, Doff B.; Li, Yu-Ming; Culver, Devore S; Alfreds, Shaun T.; Stearns, Frank; Sylvester, Karl G.; Widen, Eric

    2017-01-01

    Background Type 2 diabetes mellitus (T2DM), with increased risk of serious long-term complications, currently represents 8.3% of the adult population. We hypothesized that a critical transition state prior to the new onset T2DM can be revealed through the longitudinal electronic medical record (EMR) analysis. Method We applied the transition-based network entropy methodology which previously identified a dynamic driver network (DDN) underlying the critical T2DM transition at the tissue molecular biological level. To profile pre-disease phenotypical changes that indicated a critical transition state, a cohort of 7,334 patients was assembled from the Maine State Health Information Exchange (HIE). These patients all had their first confirmative diagnosis of T2DM between January 1, 2013 and June 30, 2013. The cohort’s EMRs from the 24 months preceding their date of first T2DM diagnosis were extracted. Results Analysis of these patients’ pre-disease clinical history identified a dynamic driver network (DDN) and an associated critical transition state six months prior to their first confirmative T2DM state. Conclusions This 6-month window before the disease state provides an early warning of the impending T2DM, warranting an opportunity to apply proactive interventions to prevent or delay the new onset of T2DM. PMID:28686739

  19. A model-based tool to predict the propagation of infectious disease via airports.

    PubMed

    Hwang, Grace M; Mahoney, Paula J; James, John H; Lin, Gene C; Berro, Andre D; Keybl, Meredith A; Goedecke, D Michael; Mathieu, Jennifer J; Wilson, Todd

    2012-01-01

    Epidemics of novel or re-emerging infectious diseases have quickly spread globally via air travel, as highlighted by pandemic H1N1 influenza in 2009 (pH1N1). Federal, state, and local public health responders must be able to plan for and respond to these events at aviation points of entry. The emergence of a novel influenza virus and its spread to the United States were simulated for February 2009 from 55 international metropolitan areas using three basic reproduction numbers (R(0)): 1.53, 1.70, and 1.90. Empirical data from the pH1N1 virus were used to validate our SEIR model. Time to entry to the U.S. during the early stages of a prototypical novel communicable disease was predicted based on the aviation network patterns and the epidemiology of the disease. For example, approximately 96% of origins (R(0) of 1.53) propagated a disease into the U.S. in under 75 days, 90% of these origins propagated a disease in under 50 days. An R(0) of 1.53 reproduced the pH1NI observations. The ability to anticipate the rate and location of disease introduction into the U.S. provides greater opportunity to plan responses based on the scenario as it is unfolding. This simulation tool can aid public health officials to assess risk and leverage resources efficiently. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Microvesicles/exosomes as potential novel biomarkers of metabolic diseases

    PubMed Central

    Müller, Günter

    2012-01-01

    Biomarkers are of tremendous importance for the prediction, diagnosis, and observation of the therapeutic success of common complex multifactorial metabolic diseases, such as type II diabetes and obesity. However, the predictive power of the traditional biomarkers used (eg, plasma metabolites and cytokines, body parameters) is apparently not sufficient for reliable monitoring of stage-dependent pathogenesis starting with the healthy state via its initiation and development to the established disease and further progression to late clinical outcomes. Moreover, the elucidation of putative considerable differences in the underlying pathogenetic pathways (eg, related to cellular/tissue origin, epigenetic and environmental effects) within the patient population and, consequently, the differentiation between individual options for disease prevention and therapy – hallmarks of personalized medicine – plays only a minor role in the traditional biomarker concept of metabolic diseases. In contrast, multidimensional and interdependent patterns of genetic, epigenetic, and phenotypic markers presumably will add a novel quality to predictive values, provided they can be followed routinely along the complete individual disease pathway with sufficient precision. These requirements may be fulfilled by small membrane vesicles, which are so-called exosomes and microvesicles (EMVs) that are released via two distinct molecular mechanisms from a wide variety of tissue and blood cells into the circulation in response to normal and stress/pathogenic conditions and are equipped with a multitude of transmembrane, soluble and glycosylphosphatidylinositol-anchored proteins, mRNAs, and microRNAs. Based on the currently available data, EMVs seem to reflect the diverse functional and dysfunctional states of the releasing cells and tissues along the complete individual pathogenetic pathways underlying metabolic diseases. A critical step in further validation of EMVs as biomarkers will rely on the identification of unequivocal correlations between critical disease states and specific EMV signatures, which in future may be determined in rapid and convenient fashion using nanoparticle-driven biosensors. PMID:22924003

  1. Myotonic Dystrophies: State of the Art of New Therapeutic Developments for the CNS

    PubMed Central

    Gourdon, Genevieve; Meola, Giovanni

    2017-01-01

    Myotonic dystrophies are multisystemic diseases characterized not only by muscle and heart dysfunction but also by CNS alteration. They are now recognized as brain diseases affecting newborns and children for myotonic dystrophy type 1 and adults for both myotonic dystrophy type 1 and type 2. In the past two decades, much progress has been made in understanding the mechanisms underlying the DM symptoms allowing development of new molecular therapeutic tools with the ultimate aim of curing the disease. This review describes the state of the art for the characterization of CNS related symptoms, the development of molecular strategies to target the CNS as well as the available tools for screening and testing new possible treatments. PMID:28473756

  2. [Peru, climate change and non-communicable diseases: ¿where are we and where are we headed?].

    PubMed

    Avilez, José L; Bazalar, Janina; Azañedo, Diego; Miranda, J Jaime

    2016-03-01

    The world is facing a crisis of noncommunicable diseases alongside a state of climate volatility. Of the total health burden attributable to climate change, 99% will be assumed by developing countries. In light of climate change, Peru's best opportunity is to create mitigation and adaptation policies focused on developing health co-benefits, which will improve the state of noncommunicable diseases and the climate system. This article presents Peru's compromises in terms of mitigation of greenhouse gas emissions; identifies public health opportunities for Peru under the Paris Agreement signed in the 21st Conference of the Parties (COP21); and makes recommendations for evidence and policy generation for the National Academy of Medicine and the Peruvian government.

  3. Active Immunization in the United States: Developments over the Past Decade

    PubMed Central

    Dennehy, Penelope H.

    2001-01-01

    The Centers for Disease Control and Prevention has identified immunization as the most important public health advance of the 20th century. The purpose of this article is to review the changes that have taken place in active immunization in the United States over the past decade. Since 1990, new vaccines have become available to prevent five infectious diseases: varicella, rotavirus, hepatitis A, Lyme disease, and Japanese encephalitis virus infection. Improved vaccines have been developed to prevent Haemophilus influenzae type b, pneumococcus, pertussis, rabies, and typhoid infections. Immunization strategies for the prevention of hepatitis B, measles, meningococcal infections, and poliomyelitis have changed as a result of the changing epidemiology of these diseases. Combination vaccines are being developed to facilitate the delivery of multiple antigens, and improved vaccines are under development for cholera, influenza, and meningococcal disease. Major advances in molecular biology have enabled scientists to devise new approaches to the development of vaccines against diseases ranging from respiratory viral to enteric bacterial infections that continue to plague the world's population. PMID:11585789

  4. Listeriosis in the far South of Brazil: neglected infection?

    PubMed

    Blum-Menezes, Dulcinéa; Deliberalli, Ivânia; Bittencourt, Najara Carneiro; Couto, Carlus Augustu Tavares do; Barbosa, Liana Nunes; Santos, Alessandro Marques dos; Pinto, Gabriel Godinho

    2013-01-01

    Listeriosis is an under-diagnosed and under-reported infection; however, listeriosis is not a compulsorily notifiable disease in Brazil. We provide an overview of the rates of listeriosis in the United States of America (USA), Europe, Latin America, and Brazil during the past decade. We also report a case of miscarriage caused by listeriosis in which there was no suspicion of this infection. This overview and the case we report serve as reminders of the often-neglected threat of listeriosis and its potential to cause miscarriage while highlighting the necessity of recognizing listeriosis as a compulsorily notifiable disease in Brazil.

  5. [Features of cardiologic diseases prevalence among individuals engaged into geology].

    PubMed

    Zinenko; Petrichenko, S I; Miroshnikov, M P; Dasaeva, L A; Vermel', A E

    2005-01-01

    The authors studied influence of work and living conditions on geologists' health state. A cohort under study demonstrated paradoxical epidemiologic situation with high mortality risk of arterial hypertension, whereas prevalence of this disease among specialists working on expeditionary shifted mode is nearly equal to that among general population. Unfavorable situation concerning cardiovascular diseases could be caused by high prevalence of cardiovascular risks and some occupational hazards. The situation is deteriorated by insufficient medical observation and psychologic traits of the specialists working on expeditionary shifted mode.

  6. [Systematization of diseases and lesions of the endometrium by etiological and pathogenetical mechanisms of development to choose an optimal treatment].

    PubMed

    Boroda, A M

    2004-03-01

    Current clinical gynecology considers pathological states of endometrium (PSE) as one of the most challenging issue of the day. Many questions of etiology, pathogenesis, diagnostics, and treatment of PSE are still under discussion. Nowadays there isn't a whole agreed classification of PSE. Morphological classification remains the most widely used one, but morphological changes occurring in the endometrium don't show a wide variety of disorders related to these pathological states. A new clinicopathogenetic classification of PSE was proposed, which is based on choosing the optimal treatment with functional state of the disease taken into account. This classification helps us to perceive the problem as a whole with choosing functionally based treatment for each patient.

  7. Parkinsonian gait improves with bilateral subthalamic nucleus deep brain stimulation during cognitive multi-tasking.

    PubMed

    Chenji, Gaurav; Wright, Melissa L; Chou, Kelvin L; Seidler, Rachael D; Patil, Parag G

    2017-05-01

    Gait impairment in Parkinson's disease reduces mobility and increases fall risk, particularly during cognitive multi-tasking. Studies suggest that bilateral subthalamic deep brain stimulation, a common surgical therapy, degrades motor performance under cognitive dual-task conditions, compared to unilateral stimulation. To measure the impact of bilateral versus unilateral subthalamic deep brain stimulation on walking kinematics with and without cognitive dual-tasking. Gait kinematics of seventeen patients with advanced Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation were examined off medication under three stimulation states (bilateral, unilateral left, unilateral right) with and without a cognitive challenge, using an instrumented walkway system. Consistent with earlier studies, gait performance declined for all six measured parameters under cognitive dual-task conditions, independent of stimulation state. However, bilateral stimulation produced greater improvements in step length and double-limb support time than unilateral stimulation, and achieved similar performance for other gait parameters. Contrary to expectations from earlier studies of dual-task motor performance, bilateral subthalamic deep brain stimulation may assist in maintaining temporal and spatial gait performance under cognitive dual-task conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Using thermal stress to model aspects of disease states.

    PubMed

    Wilson, Thad E; Klabunde, Richard E; Monahan, Kevin D

    2014-07-01

    Exposure to acute heat or cold stress elicits numerous physiological responses aimed at maintaining body temperatures. Interestingly, many of the physiological responses, mediated by the cardiovascular and autonomic nervous systems, resemble aspects of, or responses to, certain disease states. The purpose of this Perspective is to highlight some of these areas in order to explore how they may help us better understand the pathophysiology underlying aspects of certain disease states. The benefits of using this human thermal stress approach are that (1) no adjustments for inherent comparative differences in animals are needed, (2) non-medicated healthy humans with no underlying co-morbidities can be studied in place of complex patients, and (3) more mechanistic perturbations can be safely employed without endangering potentially vulnerable populations. Cold stress can be used to induce stable elevations in blood pressure. Cold stress may also be used to model conditions where increases in myocardial oxygen demand are not met by anticipated increases in coronary blood flow, as occurs in older adults. Lower-body negative pressure has the capacity to model aspects of shock, and the further addition of heat stress improves and expands this model because passive-heat exposure lowers systemic vascular resistance at a time when central blood volume and left-ventricular filling pressure are reduced. Heat stress can model aspects of heat syncope and orthostatic intolerance as heat stress decreases cerebral blood flow and alters the Frank-Starling mechanism resulting in larger decreases in stroke volume for a given change in left-ventricular filling pressure. Combined, thermal perturbations may provide in vivo paradigms that can be employed to gain insights into pathophysiological aspects of certain disease states. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. 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

  10. Disability evaluation in arthritis patients.

    PubMed

    Luck, J V; Beardmore, T D; Kaufman, R

    1987-08-01

    During the working years, rheumatic conditions are the foremost cause of disability in the United States. Disability evaluation for Social Security applicants and Workers' Compensation patients is commonplace in orthopedic practices. Yet, formal education in this aspect of patient care is rare both during and after residency. Because of a lack of understanding and sophistication the physician who knows the patient better than any other evaluator often play a minor role in the determination of disability. Disability Evaluation Under Social Security--A Handbook for Physicians lists the medical criteria necessary for qualification. Severely disabled arthritis patients will not always fit into these various categories and may have to be considered under the rule of medical equivalency. Workers' Compensation statutes vary somewhat from state to state but generally include disability criteria. Familiarity with these criteria and the process involved will allow the orthopedist to communicate more meaningfully with administrators and will reduce much of the frustration and some of the cost inherent in this system. When subjective complaint (illness) is in excess of apparent organic pathology (disease), team evaluation under the direction of the treating physician will help sort out the dilemma and develop a treatment plan. One hopes that this will bring the illness more in line with the disease, and thus reduce the disability.

  11. Human risk of infection with Borrelia burgdorferi, the Lyme disease agent, in eastern United States.

    PubMed

    Diuk-Wasser, Maria A; Hoen, Anne Gatewood; Cislo, Paul; Brinkerhoff, Robert; Hamer, Sarah A; Rowland, Michelle; Cortinas, Roberto; Vourc'h, Gwenaël; Melton, Forrest; Hickling, Graham J; Tsao, Jean I; Bunikis, Jonas; Barbour, Alan G; Kitron, Uriel; Piesman, Joseph; Fish, Durland

    2012-02-01

    The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States. The map is based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgdorferi, which is closely associated with human infection risk. Risk factors for the presence and density of infected nymphs were used to model a continuous 8 km×8 km resolution predictive surface of human risk, including confidence intervals for each pixel. Discontinuous Lyme disease risk foci were identified in the Northeast and upper Midwest, with a transitional zone including sites with uninfected I. scapularis populations. Given frequent under- and over-diagnoses of Lyme disease, this map could act as a tool to guide surveillance, control, and prevention efforts and act as a baseline for studies tracking the spread of infection.

  12. Spatial forecasting of disease risk and uncertainty

    USGS Publications Warehouse

    De Cola, L.

    2002-01-01

    Because maps typically represent the value of a single variable over 2-dimensional space, cartographers must simplify the display of multiscale complexity, temporal dynamics, and underlying uncertainty. A choropleth disease risk map based on data for polygonal regions might depict incidence (cases per 100,000 people) within each polygon for a year but ignore the uncertainty that results from finer-scale variation, generalization, misreporting, small numbers, and future unknowns. In response to such limitations, this paper reports on the bivariate mapping of data "quantity" and "quality" of Lyme disease forecasts for states of the United States. Historical state data for 1990-2000 are used in an autoregressive model to forecast 2001-2010 disease incidence and a probability index of confidence, each of which is then kriged to provide two spatial grids representing continuous values over the nation. A single bivariate map is produced from the combination of the incidence grid (using a blue-to-red hue spectrum), and a probabilistic confidence grid (used to control the saturation of the hue at each grid cell). The resultant maps are easily interpretable, and the approach may be applied to such problems as detecting unusual disease occurences, visualizing past and future incidence, and assembling a consistent regional disease atlas showing patterns of forecasted risks in light of probabilistic confidence.

  13. Targeting the complement system for the management of retinal inflammatory and degenerative diseases.

    PubMed

    Xu, Heping; Chen, Mei

    2016-09-15

    The retina, an immune privileged tissue, has specialized immune defense mechanisms against noxious insults that may exist in diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), uveoretinitis and glaucoma. The defense system consists of retinal innate immune cells (including microglia, perivascular macrophages, and a small population of dendritic cells) and the complement system. Under normal aging conditions, retinal innate immune cells and the complement system undergo a low-grade activation (parainflammation) which is important for retinal homeostasis. In disease states such as AMD and DR, the parainflammatory response is dysregulated and develops into detrimental chronic inflammation. Complement activation in the retina is an important part of chronic inflammation and may contribute to retinal pathology in these disease states. Here, we review the evidence that supports the role of uncontrolled or dysregulated complement activation in various retinal degenerative and angiogenic conditions. We also discuss current strategies that are used to develop complement-based therapies for retinal diseases such as AMD. The potential benefits of complement inhibition in DR, uveoretinitis and glaucoma are also discussed, as well as the need for further research to better understand the mechanisms of complement-mediated retinal damage in these disease states. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Mortality Trends for Neglected Tropical Diseases in the State of Sergipe, Brazil, 1980-2013.

    PubMed

    Costa de Albuquerque, Marcos Antônio; Dias, Danielle Menezes; Vieira, Lucas Teixeira; Lima, Carlos Anselmo; da Silva, Angela Maria

    2017-02-08

    Neglected Tropical Diseases are a set of communicable diseases that affect the population so low socioeconomic status, particularly 1.4 billion people who are living below the poverty level. This study has investigated the magnitude and mortality time trends for these diseases in the state of Sergipe, Northeast Region of Brazil. We conducted an ecological study of time series, based on secondary data derived from the Mortality Information System of the Ministry of Health. The mortality rates (crude, age-standardized rates and proportional ratio) were calculated from the deaths due to Neglected Tropical Diseases in the state of Sergipe, from 1980 to 2013. The time trends were obtained using the Joinpoint regression model. Three hundred six thousand and eight hundred seventy-two deaths were certified in the state and Neglected Tropical Diseases were mentioned as the underlying cause in 1,203 certificates (0.39%). Mean number of deaths was 35.38 per year, and crude and age-standardized mortality rates were, respectively: 2.16 per 100 000 inhabitants (95% CI: 1.45-2.87) and 2.87 per 100 000 inhabitants (95% CI: 1.93-3.82); the proportional mortality ratio was 0.41% (95% CI: 0.27-0.54). In that period, Schistosomiasis caused 654 deaths (54.36%), followed by Chagas disease, with 211 (17.54%), and by Leishmaniases, with 142 (11.80%) deaths. The other diseases totalized 196 deaths (16.30%). There were increasing mortality trends for Neglected Tropical Diseases, Schistosomiasis and Chagas disease in the last 15 years, according to the age-standardized rates, and stability of the mortality trends for Leishmaniases. The Neglected Tropical Diseases show increasing trends and are a real public health problem in the state of Sergipe, since they are responsible for significant mortality rates. The following diseases call attention for showing greater number of deaths in the period of study: Schistosomiasis, Chagas disease and Leishmaniases. We finally suggest that public managers take appropriate actions to develop new strategies in epidemiological and therapeutic surveillance, and in the follow-up of these patients.

  15. Immunological features underlying viral hemorrhagic fevers.

    PubMed

    Messaoudi, Ilhem; Basler, Christopher F

    2015-10-01

    Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Folding of Cu/Zn superoxide dismutase suggests structural hotspots for gain of neurotoxic function in ALS: Parallels to precursors in amyloid disease

    PubMed Central

    Nordlund, Anna; Oliveberg, Mikael

    2006-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease linked to misfolding of the ubiquitous enzyme Cu/Zn superoxide dismutase (SOD). In contrast to other protein-misfolding disorders with similar neuropathogenesis, ALS is not always associated with the in vivo deposition of protein aggregates. Thus, under the assumption that all protein-misfolding disorders share at primary level a similar disease mechanism, ALS constitutes an interesting disease model for identifying the yet-mysterious precursor states from which the cytotoxic pathway emerges. In this study, we have mapped out the conformational repertoire of the apoSOD monomer through analysis of its folding behavior. The results allow us to target the regions of the SOD structure that are most susceptible to unfolding locally under physiological conditions, leading to the exposure of structurally promiscuous interfaces that are normally hidden in the protein’s interior. The structure of this putative ALS precursor is strikingly similar to those implicated in amyloid disease. PMID:16798882

  17. Mastocytosis: current treatment concepts.

    PubMed

    Worobec, Alexandra S; Metcalfe, Dean D

    2002-02-01

    An explosion of research on mastocytosis in the last decade has witnessed a greater understanding of the molecular basis of this heterogeneous group of disorders and the conclusion that similar disease phenotypes may indeed be the result of different underlying genotypes. Along with our growing knowledge base of mastocytosis, newer approaches of treating these disorders are becoming available, all under investigational use at this time. This short review highlights the state of the art of current treatment strategies for the different categories of mastocytosis. The future will undoubtedly witness an even greater array of therapeutic options, as we continue to learn more about this enigmatic disease. Copyright 2002 S. Karger AG, Basel

  18. Incidence of rubella in a state in North-western Nigeria: a call for action.

    PubMed

    Omoleke, Semeeh Akinwale; Udenenwu, Henry Chukwuebuka

    2016-01-01

    Rubella cases are often under-reported, especially in many developing countries, owing to inadequate attention and weak funding of elimination strategies, despite being an epidemic-prone disease. Based on available data, this paper, therefore, seeks to bring the attention of public health practitioners, researchers and policy makers to threats of rubella in our environment, and also recommend measures to mitigate the threats. The authors conducted a retrospective cross-sectional study in which the laboratory results of febrile-rash-illness cases in Kebbi State, Northwest Nigeria, from January 1, 2014 to December 31, 2015 were analysed, using descriptive statistics and chi-square test. We obtained the data set through the routine Integrated Disease Surveillance System and Response being conducted in Nigeria. A total of 413 febrile-rash-illness cases were reported and investigated in Kebbi State from 2014 to 2015, 5 (3.5%) tested positive for rubella IgM in 2014 while 7(2.6%) tested positive in 2015. There was no statistically significant difference in the incidence of rubella between 2014 and 2015 (p> 0.05). Rubella infection was mainly found in children less than 5 years of age with peak incidence period during the hot season (between February and April). There was no significant sex bias in this study. However, our practice experiences in this environment suggest a systematic under-reporting and under-diagnosis of febrile- rash-illnesses. There was no statistically significant difference in the incidence of rubella in children in our setting for the 2-years studied. However, there is a potential for increase in the transmission of the disease due to non-availability of routine childhood vaccination against rubella and the systematic under-reporting of suspected cases and weak laboratory support. In order to better appreciate the burden of rubella infection, there may be a need to undertake a prevalence survey, and simultaneously, strengthening case-based surveillance in Northwestern Nigeria. Further, WHO should support national government in accelerating the introduction of rubella-containing vaccine to stem the potential spread of this infectious disease.

  19. Incidence of rubella in a state in North-western Nigeria: a call for action

    PubMed Central

    Omoleke, Semeeh Akinwale; Udenenwu, Henry Chukwuebuka

    2016-01-01

    Introduction Rubella cases are often under-reported, especially in many developing countries, owing to inadequate attention and weak funding of elimination strategies, despite being an epidemic-prone disease. Based on available data, this paper, therefore, seeks to bring the attention of public health practitioners, researchers and policy makers to threats of rubella in our environment, and also recommend measures to mitigate the threats. Methods The authors conducted a retrospective cross-sectional study in which the laboratory results of febrile-rash-illness cases in Kebbi State, Northwest Nigeria, from January 1, 2014 to December 31, 2015 were analysed, using descriptive statistics and chi-square test. We obtained the data set through the routine Integrated Disease Surveillance System and Response being conducted in Nigeria. Results A total of 413 febrile-rash-illness cases were reported and investigated in Kebbi State from 2014 to 2015, 5 (3.5%) tested positive for rubella IgM in 2014 while 7(2.6%) tested positive in 2015. There was no statistically significant difference in the incidence of rubella between 2014 and 2015 (p> 0.05). Rubella infection was mainly found in children less than 5 years of age with peak incidence period during the hot season (between February and April). There was no significant sex bias in this study. However, our practice experiences in this environment suggest a systematic under-reporting and under-diagnosis of febrile- rash-illnesses. Conclusion There was no statistically significant difference in the incidence of rubella in children in our setting for the 2-years studied. However, there is a potential for increase in the transmission of the disease due to non-availability of routine childhood vaccination against rubella and the systematic under-reporting of suspected cases and weak laboratory support. In order to better appreciate the burden of rubella infection, there may be a need to undertake a prevalence survey, and simultaneously, strengthening case-based surveillance in Northwestern Nigeria. Further, WHO should support national government in accelerating the introduction of rubella-containing vaccine to stem the potential spread of this infectious disease. PMID:28250873

  20. Canopy Vegetation Indices from In situ Hyperspectral Data to Assess Plant Water Status of Winter Wheat under Powdery Mildew Stress

    PubMed Central

    Feng, Wei; Qi, Shuangli; Heng, Yarong; Zhou, Yi; Wu, Yapeng; Liu, Wandai; He, Li; Li, Xiao

    2017-01-01

    Plant disease and pests influence the physiological state and restricts the healthy growth of crops. Physiological measurements are considered the most accurate way of assessing plant health status. In this paper, we researched the use of an in situ hyperspectral remote sensor to detect plant water status in winter wheat infected with powdery mildew. Using a diseased nursery field and artificially inoculated open field experiments, we detected the canopy spectra of wheat at different developmental stages and under different degrees of disease severity. At the same time, destructive sampling was carried out for physical tests to investigate the change of physiological parameters under the condition of disease. Selected vegetation indices (VIs) were mostly comprised of green bands, and correlation coefficients between these common VIs and plant water content (PWC) were generally 0.784–0.902 (p < 0.001), indicating the green waveband may have great potential in the evaluation of water content of winter wheat under powdery mildew stress. The Photochemical Reflectance Index (PRI) was sensitive to physiological response influenced by powdery mildew, and the relationships of PRI with chlorophyll content, the maximum quantum efficiency of PSII photochemistry (Fv/Fm), and the potential activity of PSII photochemistry (Fv/Fo) were good with R2 = 0.639, 0.833, 0.808, respectively. Linear regressions showed PRI demonstrated a steady relationship with PWC across different growth conditions, with R2 = 0.817 and RMSE = 2.17. The acquired PRI model of wheat under the powdery mildew stress has a good compatibility to different experimental fields from booting stage to filling stage compared with the traditional water signal vegetation indices, WBI, FWBI1, and FWBI2. The verification results with independent data showed that PRI still performed better with R2 = 0.819 between measured and predicted, and corresponding RE = 8.26%. Thus, PRI is recommended as a potentially reliable indicator of PWC in winter wheat with powdery mildew stress. The results will help to understand the physical state of the plant, and provide technical support for disease control using remote sensing during wheat production. PMID:28751904

  1. Canopy Vegetation Indices from In situ Hyperspectral Data to Assess Plant Water Status of Winter Wheat under Powdery Mildew Stress.

    PubMed

    Feng, Wei; Qi, Shuangli; Heng, Yarong; Zhou, Yi; Wu, Yapeng; Liu, Wandai; He, Li; Li, Xiao

    2017-01-01

    Plant disease and pests influence the physiological state and restricts the healthy growth of crops. Physiological measurements are considered the most accurate way of assessing plant health status. In this paper, we researched the use of an in situ hyperspectral remote sensor to detect plant water status in winter wheat infected with powdery mildew. Using a diseased nursery field and artificially inoculated open field experiments, we detected the canopy spectra of wheat at different developmental stages and under different degrees of disease severity. At the same time, destructive sampling was carried out for physical tests to investigate the change of physiological parameters under the condition of disease. Selected vegetation indices (VIs) were mostly comprised of green bands, and correlation coefficients between these common VIs and plant water content (PWC) were generally 0.784-0.902 ( p < 0.001), indicating the green waveband may have great potential in the evaluation of water content of winter wheat under powdery mildew stress. The Photochemical Reflectance Index (PRI) was sensitive to physiological response influenced by powdery mildew, and the relationships of PRI with chlorophyll content, the maximum quantum efficiency of PSII photochemistry (Fv/Fm), and the potential activity of PSII photochemistry (Fv/Fo) were good with R 2 = 0.639, 0.833, 0.808, respectively. Linear regressions showed PRI demonstrated a steady relationship with PWC across different growth conditions, with R 2 = 0.817 and RMSE = 2.17. The acquired PRI model of wheat under the powdery mildew stress has a good compatibility to different experimental fields from booting stage to filling stage compared with the traditional water signal vegetation indices, WBI, FWBI 1 , and FWBI 2 . The verification results with independent data showed that PRI still performed better with R 2 = 0.819 between measured and predicted, and corresponding RE = 8.26%. Thus, PRI is recommended as a potentially reliable indicator of PWC in winter wheat with powdery mildew stress. The results will help to understand the physical state of the plant, and provide technical support for disease control using remote sensing during wheat production.

  2. Classification of cardiac patient states using artificial neural networks

    PubMed Central

    Kannathal, N; Acharya, U Rajendra; Lim, Choo Min; Sadasivan, PK; Krishnan, SM

    2003-01-01

    Electrocardiogram (ECG) is a nonstationary signal; therefore, the disease indicators may occur at random in the time scale. This may require the patient be kept under observation for long intervals in the intensive care unit of hospitals for accurate diagnosis. The present study examined the classification of the states of patients with certain diseases in the intensive care unit using their ECG and an Artificial Neural Networks (ANN) classification system. The states were classified into normal, abnormal and life threatening. Seven significant features extracted from the ECG were fed as input parameters to the ANN for classification. Three neural network techniques, namely, back propagation, self-organizing maps and radial basis functions, were used for classification of the patient states. The ANN classifier in this case was observed to be correct in approximately 99% of the test cases. This result was further improved by taking 13 features of the ECG as input for the ANN classifier. PMID:19649222

  3. [Effect of different therapy options on bronchial contraction in rats with modeled obstructive pulmonary disease].

    PubMed

    Kuzubova, N A; Fedin, A N; Lebedeva, E S; Platonova, I S

    2014-09-01

    In the model of chronic obstructive pulmonary disease, produced in rats by 60-day exposure to nitrogen dioxide, the effect of different options of combination therapy (corticosteroids, anticholinergics, adrenergic agonists) on the functional state of the bronchi was studied. The contractile activity of strips of the bronchi caused by nerve or smooth muscle stimulation was evaluated. Corticosteroid monotherapy resulted in deterioration of the functional state of the bronchial wall neuromuscular apparatus due to corticosteroid resistance, evolving under the influence of long-term exposure to nitrogen dioxide. Application of M-anticholinergic tiotropium had a beneficial effect on the functional state of the bronchi smooth muscles, leading to the full restoration of the bronchial wall contractile activity and removal the morphological manifestations of inflammatory lung tissue remodeling. Most effective in terms of impact on the functional state of the bronchial wall neuromuscular apparatus was corticosteroid therapy combined with M-cholinolytik or beta2-adrenoagonist.

  4. [Demographic characteristics and mortality among indigenous peoples in Mato Grosso do Sul State, Brazil].

    PubMed

    Ferreira, Maria Evanir Vicente; Matsuo, Tiemi; Souza, Regina Kazue Tanno de

    2011-12-01

    The present study aimed to assess mortality rates and related demographic factors among indigenous peoples in the State of Mato Grosso do Sul, Central-West Brazil, compared to the State's general population. Mortality rates were estimated based on data obtained from the Health Care Database for Indigenous Peoples and monthly patient care records as well as demographic data from the Brazilian Unified National Health System (SUS) and mortality data from the SUS Mortality Database. Compared to the overall population, among indigenous peoples there were proportionally more individuals under 15 years of age and fewer elderly, besides higher mortality rates at early ages and from infectious and parasitic diseases. Indigenous men showed significantly higher mortality rates from external causes and respiratory and infectious diseases, while among women the mortality rates from external causes and infectious diseases were higher. Suicide rates among young indigenous individuals were also particularly alarming. Indigenous people's health conditions are worse than those of the general population in Mato Grosso do Sul.

  5. [Oxygen-transporting function of the blood circulation system in sevoflurane anesthesia during myocardial revascularization under extracorporeal circulation].

    PubMed

    Skopets, A A; Lomivorotov, V V; Karakhalis, N B; Makarov, A A; Duman'ian, E S; Lomivorotova, L V

    2009-01-01

    The purpose of the study was to evaluate the efficiency of oxygen-transporting function of the circulatory system under sevoflurane anesthesia during myocardial revascularization operations under extracorporeal circulation. Twenty-five patients with coronary heart disease were examined. Mean blood pressure, heart rate, cardiac index, total peripheral vascular resistance index, pulmonary pressure, pulmonary wedge pressure, and central venous pressure were measured. Arterial and mixed venous blood oxygen levels, oxygen delivery and consumption index, arteriovenous oxygen difference, and glucose and lactate concentrations were calculated. The study has demonstrated that sevoflurane is an effective and safe anesthetic for myocardial revascularization operations in patients with coronary heart disease. The use of sevoflurane contributes to steady-state oxygen-transporting function of the circulatory system at all surgical stages.

  6. 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.

  7. Herd Immunity Against Foot-and-Mouth Disease Under Different Vaccination Practices in India.

    PubMed

    Sharma, G K; Mahajan, S; Matura, R; Biswal, J K; Ranjan, R; Subramaniam, S; Misri, J; Bambal, R G; Pattnaik, B

    2017-08-01

    A systematic vaccination programme is ongoing in India to control the three prevailing serotypes (A, O, Asia1) of foot-and-mouth disease (FMD) virus. Under the programme, more than 120 million bovine (term bovine applicable to both cattle and buffalo in this study) population of 221 of the 666 districts in the country are being bi-annually vaccinated with trivalent vaccine since 2010. Although clinical disease has reduced in these districts because of the systematic vaccinations, an abrupt increase in the number of FMD cases was recorded in 2013. Hence, a longitudinal field study was conducted in the year 2014 to estimate the serological herd immunity level in bovines, the impact of systematic vaccinations and field efficacy of the vaccines used. Serum samples (n = 115 963) collected from 295 districts of the 18 states of the country were analysed to estimate antibody titres against structural proteins of the three serotypes. The efficacy of the vaccine was demonstrated in the control group (group-D) where animals of the group were identified by ear tags for the purpose of repeated sampling after vaccination. Progressive building of the herd immunity in the field after systematic vaccination was demonstrated. The mean antibody titre against the serotypes O, A and Asia1 was estimated as log 10 1.93 (95% CI 1.92-1.93), 2.02 (2.02-2.02) and 2.02 (2.02-2.02), respectively, in the states covered under the control programme. However, in other states herd immunity was significantly low [mean titre log 10 1.68 (95% CI 1.67-1.69), 1.77 (1.76-1.78) and 1.85 (1.84-1.86) against the three serotypes]. Inverse relationship between the herd immunity and FMD incidences was observed the states following different vaccination practices. The study helped in demarcation of FMD risk zones in the country with low herd immunity. Estimation of herd immunity kinetics in the field helped in refining the vaccination schedule under the control programme. © 2016 Blackwell Verlag GmbH.

  8. Bacterial profiling of White Plague Disease across corals and oceans indicates a conserved and distinct disease microbiome

    PubMed Central

    Roder, Cornelia; Arif, Chatchanit; Daniels, Camille; Weil, Ernesto; Voolstra, Christian R

    2014-01-01

    Coral diseases are characterized by microbial community shifts in coral mucus and tissue, but causes and consequences of these changes are vaguely understood due to the complexity and dynamics of coral-associated bacteria. We used 16S rRNA gene microarrays to assay differences in bacterial assemblages of healthy and diseased colonies displaying White Plague Disease (WPD) signs from two closely related Caribbean coral species, Orbicella faveolata and Orbicella franksi. Analysis of differentially abundant operational taxonomic units (OTUs) revealed strong differences between healthy and diseased specimens, but not between coral species. A subsequent comparison to data from two Indo-Pacific coral species (Pavona duerdeni and Porites lutea) revealed distinct microbial community patterns associated with ocean basin, coral species and health state. Coral species were clearly separated by site, but also, the relatedness of the underlying bacterial community structures resembled the phylogenetic relationship of the coral hosts. In diseased samples, bacterial richness increased and putatively opportunistic bacteria were consistently more abundant highlighting the role of opportunistic conditions in structuring microbial community patterns during disease. Our comparative analysis shows that it is possible to derive conserved bacterial footprints of diseased coral holobionts that might help in identifying key bacterial species related to the underlying etiopathology. Furthermore, our data demonstrate that similar-appearing disease phenotypes produce microbial community patterns that are consistent over coral species and oceans, irrespective of the putative underlying pathogen. Consequently, profiling coral diseases by microbial community structure over multiple coral species might allow the development of a comparative disease framework that can inform on cause and relatedness of coral diseases. PMID:24350609

  9. The functional implications of motor, cognitive, psychiatric, and social problem-solving states in Huntington's disease.

    PubMed

    Van Liew, Charles; Gluhm, Shea; Goldstein, Jody; Cronan, Terry A; Corey-Bloom, Jody

    2013-01-01

    Huntington's disease (HD) is a genetic, neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction. In HD, the inability to solve problems successfully affects not only disease coping, but also interpersonal relationships, judgment, and independent living. The aim of the present study was to examine social problem-solving (SPS) in well-characterized HD and at-risk (AR) individuals and to examine its unique and conjoint effects with motor, cognitive, and psychiatric states on functional ratings. Sixty-three participants, 31 HD and 32 gene-positive AR, were included in the study. Participants completed the Social Problem-Solving Inventory-Revised: Long (SPSI-R:L), a 52-item, reliable, standardized measure of SPS. Items are aggregated under five scales (Positive, Negative, and Rational Problem-Solving; Impulsivity/Carelessness and Avoidance Styles). Participants also completed the Unified Huntington's Disease Rating Scale functional, behavioral, and cognitive assessments, as well as additional neuropsychological examinations and the Symptom Checklist-90-Revised (SCL-90R). A structural equation model was used to examine the effects of motor, cognitive, psychiatric, and SPS states on functionality. The multifactor structural model fit well descriptively. Cognitive and motor states uniquely and significantly predicted function in HD; however, neither psychiatric nor SPS states did. SPS was, however, significantly related to motor, cognitive, and psychiatric states, suggesting that it may bridge the correlative gap between psychiatric and cognitive states in HD. SPS may be worth assessing in conjunction with the standard gamut of clinical assessments in HD. Suggestions for future research and implications for patients, families, caregivers, and clinicians are discussed.

  10. Synchrony of two uncoupled neurons under half wave sine current stimulation

    NASA Astrophysics Data System (ADS)

    Peng, Yueping; Wang, Jue; Jian, Zhong

    2009-04-01

    Two uncoupled Hindmarsh-Rose neurons under different initial discharge patterns are stimulated by the half wave sine current; and the synchronization mechanism of the two neurons is discussed by analyzing their membrane potentials and their interspike interval (ISI) distribution. Under the half wave sine current stimulation, the two uncoupled neurons under different initial conditions, whose parameter r (the parameter r is related to the membrane penetration of calcium ion, and reflects the changing speed of the slow adaptation current) is different or the same, can realize discharge synchronization (phase synchronization) or the full synchronization (state synchronization). The synchronization characteristics are mainly related to the frequency and the amplitude of the half wave sine current, and are little related to the parameter r and the initial state of the two neurons. This investigation shows the mechanism of the current's amplitude and its frequency affecting the synchronization process of neurons, and the neurons' discharge patterns and synchronization process can be adjusted and controlled by the current's amplitude and its frequency. This result is of far reaching importance to study synchronization and encode of many neurons or neural network, and provides the theoretic basis for studying the mechanism of some nervous diseases such as epilepsy and Alzheimer's disease by the slow wave of EEG.

  11. Access to benznidazole for Chagas disease in the United States-Cautious optimism?

    PubMed

    Alpern, Jonathan D; Lopez-Velez, Rogelio; Stauffer, William M

    2017-09-01

    Drugs for neglected tropical diseases (NTD) are being excessively priced in the United States. Benznidazole, the first-line drug for Chagas disease, may become approved by the Food and Drug Administration (FDA) and manufactured by a private company in the US, thus placing it at risk of similar pricing. Chagas disease is an NTD caused by Trypanosoma cruzi; it is endemic to Latin America, infecting 8 million individuals. Human migration has changed the epidemiology causing nonendemic countries to face increased challenges in diagnosing and managing patients with Chagas disease. Only 2 drugs exist with proven efficacy: benznidazole and nifurtimox. Benznidazole has historically faced supply problems and drug shortages, limiting accessibility. In the US, it is currently only available under an investigational new drug (IND) protocol from the CDC and is provided free of charge to patients. However, 2 companies have stated that they intend to submit a New Drug Application (NDA) for FDA approval. Based on recent history of companies acquiring licensing rights for NTD drugs in the US with limited availability, it is likely that benznidazole will become excessively priced by the manufacturer-paradoxically making it less accessible. However, if the companies can be taken at their word, there may be reason for optimism.

  12. Chagas disease study using satellite image processing: A Bolivian case

    NASA Astrophysics Data System (ADS)

    Vargas-Cuentas, Natalia I.; Roman-Gonzalez, Avid; Mantari, Alicia Alva; Muñoz, Luis AnthonyAucapuma

    2018-03-01

    Remote sensing is the technology that has enabled us to obtain information about the Earth's surface without directly contacting it. For this reason, currently, the Bolivian state has considered a list of interesting applications of remote sensing in the country, including the following: biodiversity and environment monitoring, mining and geology, epidemiology, agriculture, water resources and land use planning. The use of satellite images has become a great tool for epidemiology because with this technological advance we can determine the environment in which transmission occurs, the distribution of the disease and its evolution over time. In that context, one of the important diseases related to public health in Bolivia is Chagas disease, also known as South American Trypanosomiasis. Chagas is caused by a blood-sucking bug or Vinchuca, which causes serious intestinal and heart long term problems and affects 33.4% of the Bolivian population. This disease affects mostly humble people, so the Bolivian state invests millions of dollars to acquire medicine and distribute it for free. Due to the above reasons, the present research aims to analyze some areas of Bolivia using satellite images for developing an epidemiology study. The primary objective is to understand the environment in which the transmission of the disease happens, and the climatic conditions under which occurs, observe the behavior of the blood-sucking bug, identify in which months occur higher outbreaks, in which months the bug leaves its eggs, and under which weather conditions this happens. All this information would be contrasted with information extracted from the satellite images and data from the Ministry of Health, and the Institute of Meteorology in Bolivia. All this data will allow us to have a more integrated understanding of this disease and promote new possibilities to prevent and control it.

  13. [Learning from the US immunization administration].

    PubMed

    Kamiya, Hajime; Kamiya, Hitoshi

    2008-10-01

    The US federal government has been providing support to state and local health departments for immunization program since 1920' s. Many government and nongovernment organizations, groups and personnel are involved in the process of the US immunization program. These organizations and groups are moving towards the same direction under the policy of "reducing the incidence of vaccine preventable diseases and to increase the safe usage of vaccines and related biological products". Thus every organization keeps step with the others, which will make states and other local government easier to follow the recommendations. In this review, we will introduce the system and structure of the US immunization administration and indicate why the US has succeeded to decrease vaccine preventable disease with immunization.

  14. 78 FR 25565 - Controlled Import Permits

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-02

    ... importation into the United States of otherwise prohibited or restricted plant material for experimental... could apply to import material infected with a plant disease to test diagnostic techniques.). APHIS will... being adequate to prevent plant pest introduction. Post Entry Quarantine Under Sec. 319.37-7, certain...

  15. Culicoides-virus interactions: infection barriers and possible factors underlying vector competence

    USDA-ARS?s Scientific Manuscript database

    In the United States, Culicoides midges vector arboviruses of economic importance such as Bluetongue Virus and Epizootic Hemorrhagic Disease Virus. A limited number of studies have demonstrated the complexities of midge-virus interactions, including dynamic changes in virus titer and prevalence over...

  16. Abnormal baseline brain activity in Alzheimer's disease patients with depression: a resting-state functional magnetic resonance imaging study.

    PubMed

    Liu, Xiaozheng; Guo, Zhongwei; Ding, Yanping; Li, Jiapeng; Wang, Gang; Hou, Hongtao; Chen, Xingli; Yu, Enyan

    2017-07-01

    As one of the most common mental disorders and the most important precursor of suicide in Alzheimer's disease (AD), depression is associated with a decline in both well-being and daily functioning. At present, the diagnosis of AD patients with depression (D-AD) is largely dependent on clinical signs and symptoms, and the precise neural correlate underlying D-AD is still not fully understood. The current study sought to investigate low-frequency oscillations at the voxel level in D-AD patients based on the amplitude of low-frequency fluctuations (ALFF) measured using resting-state functional magnetic resonance imaging. We examined 22 D-AD patients and 21 non-depressed AD (nD-AD) patients. The results revealed that D-AD patients exhibited increased ALFF values in the left caudate and thalamus and decreased ALFF values in the left middle temporal pole compared with nD-AD patients. These findings may provide further insight into the underlying neuropathophysiology of AD with depression.

  17. Using the Disease State Fingerprint Tool for Differential Diagnosis of Frontotemporal Dementia and Alzheimer's Disease

    PubMed Central

    Muñoz-Ruiz, Miguel Ángel; Hall, Anette; Mattila, Jussi; Koikkalainen, Juha; Herukka, Sanna-Kaisa; Husso, Minna; Hänninen, Tuomo; Vanninen, Ritva; Liu, Yawu; Hallikainen, Merja; Lötjönen, Jyrki; Remes, Anne M.; Alafuzoff, Irina; Soininen, Hilkka; Hartikainen, Päivi

    2016-01-01

    Background Disease State Index (DSI) and its visualization, Disease State Fingerprint (DSF), form a computer-assisted clinical decision making tool that combines patient data and compares them with cases with known outcomes. Aims To investigate the ability of the DSI to diagnose frontotemporal dementia (FTD) and Alzheimer's disease (AD). Methods The study cohort consisted of 38 patients with FTD, 57 with AD and 22 controls. Autopsy verification of FTD with TDP-43 positive pathology was available for 14 and AD pathology for 12 cases. We utilized data from neuropsychological tests, volumetric magnetic resonance imaging, single-photon emission tomography, cerebrospinal fluid biomarkers and the APOE genotype. The DSI classification results were calculated with a combination of leave-one-out cross-validation and bootstrapping. A DSF visualization of a FTD patient is presented as an example. Results The DSI distinguishes controls from FTD (area under the receiver-operator curve, AUC = 0.99) and AD (AUC = 1.00) very well and achieves a good differential diagnosis between AD and FTD (AUC = 0.89). In subsamples of autopsy-confirmed cases (AUC = 0.97) and clinically diagnosed cases (AUC = 0.94), differential diagnosis of AD and FTD performs very well. Conclusions DSI is a promising computer-assisted biomarker approach for aiding in the diagnostic process of dementing diseases. Here, DSI separates controls from dementia and differentiates between AD and FTD. PMID:27703465

  18. Systems for rapidly detecting and treating persons with ebola virus disease--United States.

    PubMed

    Koonin, Lisa M; Jamieson, Denise J; Jernigan, John A; Van Beneden, Chris A; Kosmos, Christine; Harvey, Melissa Cole; Pietz, Harald; Bertolli, Jeanne; Perz, Joseph F; Whitney, Cynthia G; Halpin, Alison Sheehan-Laufer; Daley, W Randolph; Pesik, Nicki; Margolis, Gregg S; Tumpey, Abbigail; Tappero, Jordan; Damon, Inger

    2015-03-06

    The U.S. Department of Health and Human Services (HHS), CDC, other U.S. government agencies, the World Health Organization (WHO), and international partners are taking multiple steps to respond to the current Ebola virus disease (Ebola) outbreak in West Africa to reduce its toll there and to reduce the chances of international spread. At the same time, CDC and HHS are working to ensure that persons who have a risk factor for exposure to Ebola and who develop symptoms while in the United States are rapidly identified and isolated, and safely receive treatment. HHS and CDC have actively worked with state and local public health authorities and other partners to accelerate health care preparedness to care for persons under investigation (PUI) for Ebola or with confirmed Ebola. This report describes some of these efforts and their impact.

  19. Cumulative Injury

    PubMed Central

    LaDou, Joseph

    1978-01-01

    A few states, notably California, are experiencing large increases in the number and cost of disability settlements under workers' compensation. Claims of cumulative injury for coronary heart disease, hypertension, stroke, cancer and neuropsychiatric problems have all been interpreted as compensable under workers' compensation, even when these conditions are clearly related to the aging process. Legal precedents for such claims are building rapidly throughout the country. The resultant costs may lead to the demise of the workers' compensation system. The situation in California is discussed in detail including the legal aspects, cumulative injury claims by type of disease and age of claimants, legal costs to the individual and the employer, and the economic outlook for the workers' compensation insurance system. PMID:151986

  20. Nations within a nation: variations in epidemiological transition across the states of India, 1990-2016 in the Global Burden of Disease Study.

    PubMed

    2017-12-02

    18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016. Using all available data sources, the India State-Level Disease Burden Initiative estimated burden (metrics were deaths, disability-adjusted life-years [DALYs], prevalence, incidence, and life expectancy) from 333 disease conditions and injuries and 84 risk factors for each state of India from 1990 to 2016 as part of GBD 2016. We divided the states of India into four epidemiological transition level (ETL) groups on the basis of the ratio of DALYs from communicable, maternal, neonatal, and nutritional diseases (CMNNDs) to those from non-communicable diseases (NCDs) and injuries combined in 2016. We assessed variations in the burden of diseases and risk factors between ETL state groups and between states to inform a more specific health-system response in the states and for India as a whole. DALYs due to NCDs and injuries exceeded those due to CMNNDs in 2003 for India, but this transition had a range of 24 years for the four ETL state groups. The age-standardised DALY rate dropped by 36·2% in India from 1990 to 2016. The numbers of DALYs and DALY rates dropped substantially for most CMNNDs between 1990 and 2016 across all ETL groups, but rates of reduction for CMNNDs were slowest in the low ETL state group. By contrast, numbers of DALYs increased substantially for NCDs in all ETL state groups, and increased significantly for injuries in all ETL state groups except the highest. The all-age prevalence of most leading NCDs increased substantially in India from 1990 to 2016, and a modest decrease was recorded in the age-standardised NCD DALY rates. The major risk factors for NCDs, including high systolic blood pressure, high fasting plasma glucose, high total cholesterol, and high body-mass index, increased from 1990 to 2016, with generally higher levels in higher ETL states; ambient air pollution also increased and was highest in the low ETL group. The incidence rate of the leading causes of injuries also increased from 1990 to 2016. The five leading individual causes of DALYs in India in 2016 were ischaemic heart disease, chronic obstructive pulmonary disease, diarrhoeal diseases, lower respiratory infections, and cerebrovascular disease; and the five leading risk factors for DALYs in 2016 were child and maternal malnutrition, air pollution, dietary risks, high systolic blood pressure, and high fasting plasma glucose. Behind these broad trends many variations existed between the ETL state groups and between states within the ETL groups. Of the ten leading causes of disease burden in India in 2016, five causes had at least a five-times difference between the highest and lowest state-specific DALY rates for individual causes. Per capita disease burden measured as DALY rate has dropped by about a third in India over the past 26 years. However, the magnitude and causes of disease burden and the risk factors vary greatly between the states. The change to dominance of NCDs and injuries over CMNNDs occurred about a quarter century apart in the four ETL state groups. Nevertheless, the burden of some of the leading CMNNDs continues to be very high, especially in the lowest ETL states. This comprehensive mapping of inequalities in disease burden and its causes across the states of India can be a crucial input for more specific health planning for each state as is envisioned by the Government of India's premier think tank, the National Institution for Transforming India, and the National Health Policy 2017. Bill & Melinda Gates Foundation; Indian Council of Medical Research, Department of Health Research, Ministry of Health and Family Welfare, Government of India; and World Bank. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4·0 license. Published by Elsevier Ltd.. All rights reserved.

  1. The Indian Health Promotion and Disease Prevention Act of 1985. Hearing before the Select Committee on Indian Affairs. United States Senate, Ninety-Ninth Congress, First Session on S. 400. (Gallup, NM, June 1, 1985).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Select Committee on Indian Affairs.

    The document contains transcripts of a Congressional hearing on providing health promotion and disease prevention services to American Indians. The bill under consideration would add the following programs to the Indian Health Care Improvement Act (25, U.S.C. 1603): reduction of drug, alcohol, and tobacco use; improvement of nutrition and physical…

  2. THE RENIN-ANGIOTENSIN SYSTEM AND THE BIOLOGY OF SKELETAL MUSCLE: MECHANISMS OF MUSCLE WASTING IN CHRONIC DISEASE STATES.

    PubMed

    Delafontaine, Patrice; Yoshida, Tadashi

    2016-01-01

    Sarcopenia and cachexia are muscle-wasting syndromes associated with aging and with many chronic diseases such as congestive heart failure, diabetes, cancer, chronic obstructive pulmonary disease, and renal failure. While mechanisms are complex, these conditions are often accompanied by elevated angiotensin II (Ang II). We found that Ang II infusion in rodents leads to skeletal muscle wasting via alterations in insulin-like growth factor-1 signaling, increased apoptosis, enhanced muscle protein breakdown via the ubiquitin-proteasome system, and decreased appetite resulting from downregulation of hypothalamic orexigenic neuropeptides orexin and neuropeptide Y. Furthermore, Ang II inhibits skeletal muscle stem cell proliferation, leading to lowered muscle regenerative capacity. Distinct stem cell Ang II receptor subtypes are critical for regulation of muscle regeneration. In ischemic mouse congestive heart failure model skeletal muscle wasting and attenuated muscle regeneration are Ang II dependent. These data suggest that the renin-angiotensin system plays a critical role in mechanisms underlying cachexia in chronic disease states.

  3. Human Risk of Infection with Borrelia burgdorferi, the Lyme Disease Agent, in Eastern United States

    PubMed Central

    Diuk-Wasser, Maria A.; Hoen, Anne Gatewood; Cislo, Paul; Brinkerhoff, Robert; Hamer, Sarah A.; Rowland, Michelle; Cortinas, Roberto; Vourc'h, Gwenaël; Melton, Forrest; Hickling, Graham J.; Tsao, Jean I.; Bunikis, Jonas; Barbour, Alan G.; Kitron, Uriel; Piesman, Joseph; Fish, Durland

    2012-01-01

    The geographic pattern of human risk for infection with Borrelia burgdorferi sensu stricto, the tick-borne pathogen that causes Lyme disease, was mapped for the eastern United States. The map is based on standardized field sampling in 304 sites of the density of Ixodes scapularis host-seeking nymphs infected with B. burgdorferi, which is closely associated with human infection risk. Risk factors for the presence and density of infected nymphs were used to model a continuous 8 km×8 km resolution predictive surface of human risk, including confidence intervals for each pixel. Discontinuous Lyme disease risk foci were identified in the Northeast and upper Midwest, with a transitional zone including sites with uninfected I. scapularis populations. Given frequent under- and over-diagnoses of Lyme disease, this map could act as a tool to guide surveillance, control, and prevention efforts and act as a baseline for studies tracking the spread of infection. PMID:22302869

  4. Cell mechanics as a marker for diseases: Biomedical applications of AFM

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

    Rianna, Carmela; Radmacher, Manfred, E-mail: mr@biophysik.uni-bremen.de

    Many diseases are related to changes in cell mechanics. Atomic Force Microscopy (AFM) is one of the most suitable techniques allowing the investigation of both topography and mechanical properties of adherent cells with high spatial resolution under physiological conditions. Over the years the use of this technique in medical and clinical applications has largely increased, resulting in the notion of cell mechanics as a biomarker to discriminate between different physiological and pathological states of cells. Cell mechanics has proven to be a biophysical fingerprint able discerning between cell phenotypes, unraveling processes in aging or diseases, or even detecting and diagnosingmore » cellular pathologies. We will review in this report some of the works on cell mechanics investigated by AFM with clinical and medical relevance in order to clarify the state of research in this field and to highlight the role of cell mechanics in the study of pathologies, focusing on cancer, blood and cardiovascular diseases.« less

  5. Neglected Infections of Poverty in the United States of America

    PubMed Central

    Hotez, Peter J.

    2008-01-01

    In the United States, there is a largely hidden burden of diseases caused by a group of chronic and debilitating parasitic, bacterial, and congenital infections known as the neglected infections of poverty. Like their neglected tropical disease counterparts in developing countries, the neglected infections of poverty in the US disproportionately affect impoverished and under-represented minority populations. The major neglected infections include the helminth infections, toxocariasis, strongyloidiasis, ascariasis, and cysticercosis; the intestinal protozoan infection trichomoniasis; some zoonotic bacterial infections, including leptospirosis; the vector-borne infections Chagas disease, leishmaniasis, trench fever, and dengue fever; and the congenital infections cytomegalovirus (CMV), toxoplasmosis, and syphilis. These diseases occur predominantly in people of color living in the Mississippi Delta and elsewhere in the American South, in disadvantaged urban areas, and in the US–Mexico borderlands, as well as in certain immigrant populations and disadvantaged white populations living in Appalachia. Preliminary disease burden estimates of the neglected infections of poverty indicate that tens of thousands, or in some cases, hundreds of thousands of poor Americans harbor these chronic infections, which represent some of the greatest health disparities in the United States. Specific policy recommendations include active surveillance (including newborn screening) to ascertain accurate population-based estimates of disease burden; epidemiological studies to determine the extent of autochthonous transmission of Chagas disease and other infections; mass or targeted treatments; vector control; and research and development for new control tools including improved diagnostics and accelerated development of a vaccine to prevent congenital CMV infection and congenital toxoplasmosis. PMID:18575621

  6. The Immune System: Basis of so much Health and Disease: 2. Innate Immunity.

    PubMed

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-03-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covering innate immunity. Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  7. The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

    PubMed

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-04-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  8. New Meningococcal Vaccine Recommendations under Consideration

    ERIC Educational Resources Information Center

    Turner, James C.

    2004-01-01

    The Advisory Committee on Immunization Practices (ACIP) at the Center for Disease Control and Prevention (CDC) will be considering a new vaccination recommendation for the prevention of invasive "N. meningitidis" infection when meningococcal conjugate vaccines are licensed in the United States. The CDC has also updated the Working Group…

  9. Marijuana and Children. Position Statement

    ERIC Educational Resources Information Center

    Endsley, Patricia; Embrey, Mary Louise

    2014-01-01

    Registered professional school nurses (hereinafter referred to as school nurses) promote wellness and disease prevention to improve health outcomes for our nation's children. It is the position of the National Association of School Nurses (NASN) that the marijuana plant remain under the United States Drug Enforcement Agency's (DEA) Schedule I…

  10. Aspergillus in chronic lung disease: Modeling what goes on in the airways.

    PubMed

    Takazono, Takahiro; Sheppard, Donald C

    2017-01-01

    Aspergillus species cause a range of respiratory diseases in humans. While immunocompromised patients are at risk for the development of invasive infection with these opportunistic molds, patients with underlying pulmonary disease can develop chronic airway infection with Aspergillus species. These conditions span a range of inflammatory and allergic diseases including Aspergillus bronchitis, allergic bronchopulmonary aspergillosis, and severe asthma with fungal sensitization. Animal models are invaluable tools for the study of the molecular mechanism underlying the colonization of airways by Aspergillus and the host response to these non-invasive infections. In this review we summarize the state-of-the-art with respect to the available animal models of noninvasive and allergic Aspergillus airway disease; the key findings of host-pathogen interaction studies using these models; and the limitations and future directions that should guide the development and use of models for the study of these important pulmonary conditions. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. ASM LabCap's contributions to disease surveillance and the International Health Regulations (2005).

    PubMed

    Specter, Steven; Schuermann, Lily; Hakiruwizera, Celestin; Sow, Mah-Séré Keita

    2010-12-03

    The revised International Health Regulations [IHR(2005)], which requires the Member States of the World Health Organization (WHO) to develop core capacities to detect, assess, report, and respond to public health threats, is bringing new challenges for national and international surveillance systems. As more countries move toward implementation and/or strengthening of their infectious disease surveillance programs, the strengthening of clinical microbiology laboratories becomes increasingly important because they serve as the first line responders to detect new and emerging microbial threats, re-emerging infectious diseases, the spread of antibiotic resistance, and the possibility of bioterrorism. In fact, IHR(2005) Core Capacity #8, "Laboratory", requires that laboratory services be a part of every phase of alert and response.Public health laboratories in many resource-constrained countries require financial and technical assistance to build their capacity. In recognition of this, in 2006, the American Society for Microbiology (ASM) established an International Laboratory Capacity Building Program, LabCap, housed under the ASM International Board. ASM LabCap utilizes ASM's vast resources and its membership's expertise-40,000 microbiologists worldwide-to strengthen clinical and public health laboratory systems in low and low-middle income countries. ASM LabCap's program activities align with HR(2005) by building the capability of resource-constrained countries to develop quality-assured, laboratory-based information which is critical to disease surveillance and the rapid detection of disease outbreaks, whether they stem from natural, deliberate or accidental causes.ASM LabCap helps build laboratory capacity under a cooperative agreement with the U.S. Centers for Disease Control and Prevention (CDC) and under a sub-contract with the Program for Appropriate Technology in Health (PATH) funded by the United States Agency for International Development (USAID). Successful activities of ASM LabCap have occurred throughout Africa, Asia, Central America and the Caribbean. In addition, ASM LabCap coordinates efforts with international agencies such as the WHO in order to maximize resources and ensure a unified response, with the intended goal to help build integrated disease surveillance and response capabilities worldwide in compliance with HR(2005)'s requirements.

  12. Regulation of hepatic ABCC transporters by xenobiotics and in disease states

    PubMed Central

    Gu, Xinsheng; Manautou, Jose E.

    2015-01-01

    The subfamily of ABCC transporters consists of 13 members in mammals, including the multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and the cystic fibrosis transmembrane conductance regulator (CFTR). These proteins play roles in chemical detoxification, disposition, and normal cell physiology. ABCC transporters are expressed differentially in the liver and are regulated at the transcription and translation level. Their expression and function are also controlled by post-translational modification and membrane-trafficking events. These processes are tightly regulated. Information about alterations in the expression of hepatobiliary ABCC transporters could provide important insights into the pathogenesis of diseases and disposition of xenobiotics. In this review, we describe the regulation of hepatic ABCC transporters in humans and rodents by a variety of xenobiotics, under disease states and in genetically modified animal models deficient in transcription factors, transporters, and cell-signaling molecules. PMID:20233023

  13. Using memories to understand others: the role of episodic memory in theory of mind impairment in Alzheimer disease.

    PubMed

    Moreau, Noémie; Viallet, François; Champagne-Lavau, Maud

    2013-09-01

    Theory of mind (TOM) refers to the ability to infer one's own and other's mental states. Growing evidence highlighted the presence of impairment on the most complex TOM tasks in Alzheimer disease (AD). However, how TOM deficit is related to other cognitive dysfunctions and more specifically to episodic memory impairment - the prominent feature of this disease - is still under debate. Recent neuroanatomical findings have shown that remembering past events and inferring others' states of mind share the same cerebral network suggesting the two abilities share a common process .This paper proposes to review emergent evidence of TOM impairment in AD patients and to discuss the evidence of a relationship between TOM and episodic memory. We will discuss about AD patients' deficit in TOM being possibly related to their difficulties in recollecting memories of past social interactions. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Global Diffusion Pattern and Hot SPOT Analysis of Vaccine-Preventable Diseases

    NASA Astrophysics Data System (ADS)

    Jiang, Y.; Fan, F.; Zanoni, I. Holly; Li, Y.

    2017-10-01

    Spatial characteristics reveal the concentration of vaccine-preventable disease in Africa and the Near East and that disease dispersion is variable depending on disease. The exception is whooping cough, which has a highly variable center of concentration from year to year. Measles exhibited the only statistically significant spatial autocorrelation among all the diseases under investigation. Hottest spots of measles are in Africa and coldest spots are in United States, warm spots are in Near East and cool spots are in Western Europe. Finally, cases of measles could not be explained by the independent variables, including Gini index, health expenditure, or rate of immunization. Since the literature confirms that each of the selected variables is considered determinants of disease dissemination, it is anticipated that the global dataset of disease cases was influenced by reporting bias.

  15. Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential.

    PubMed

    Thompson, Brian R; Metzger, Joseph M

    2014-09-01

    The cardiac sarcomere is the functional unit for myocyte contraction. Ordered arrays of sarcomeric proteins, held in stoichiometric balance with each other, respond to calcium to coordinate contraction and relaxation of the heart. Altered sarcomeric structure-function underlies the primary basis of disease in multiple acquired and inherited heart disease states. Hypertrophic and restrictive cardiomyopathies are caused by inherited mutations in sarcomeric genes and result in altered contractility. Ischemia-mediated acidosis directly alters sarcomere function resulting in decreased contractility. In this review, we highlight the use of acute genetic engineering of adult cardiac myocytes through stoichiometric replacement of sarcomeric proteins in these disease states with particular focus on cardiac troponin I. Stoichiometric replacement of disease causing mutations has been instrumental in defining the molecular mechanisms of hypertrophic and restrictive cardiomyopathy in a cellular context. In addition, taking advantage of stoichiometric replacement through gene therapy is discussed, highlighting the ischemia-resistant histidine-button, A164H cTnI. Stoichiometric replacement of sarcomeric proteins offers a potential gene therapy avenue to replace mutant proteins, alter sarcomeric responses to pathophysiologic insults, or neutralize altered sarcomeric function in disease. © 2014 Wiley Periodicals, Inc.

  16. Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

    PubMed Central

    Rhee, Connie M.; Brent, Gregory A.; Kovesdy, Csaba P.; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J.; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

    2015-01-01

    Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. PMID:24574542

  17. 24 CFR 582.330 - Nondiscrimination and equal opportunity requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... diseases). However, other eligible disabled homeless persons must be considered for housing designed for....C. 1301 et seq.) applies to tribes when they exercise their powers of self-government, and to IHAs when established by the exercise of such powers. When an IHA is established under State law, the...

  18. 75 FR 60416 - Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-30

    ... suffering from personal injuries and receiving medical care at Government expense. The information is... medical care provided by the United States to a person who is injured or suffers a disease under.... The name and address of the employer is collected when the injury was work related. Section 3 of the...

  19. 9 CFR 50.14 - Claims not allowed.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS... tuberculosis will not be allowed in any of the following cases: (a) The claimant has failed to comply with any... in the claimant's herd have not been tested for tuberculosis under APHIS or State supervision...

  20. 7 CFR 3430.1 - Applicability of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... supplementary to the USDA uniform assistance regulations at 7 CFR parts 3016 (State, local, and tribal..., 1890 Land-Grant Institutions, and forestry schools under the McIntire-Stennis Cooperative Forestry Act (16 U.S.C. 582a, et seq.); and animal health and disease research funds provided to veterinary schools...

  1. 9 CFR 98.10 - Other importations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... EMBRYOS AND ANIMAL SEMEN Ruminant and Swine Embryos from Regions Free of Rinderpest and Foot-and-Mouth Disease; and Embryos of Horses and Asses § 98.10 Other importations. Notwithstanding other provisions in... States of embryos other than as provided for in this part under such conditions as the Administrator may...

  2. 9 CFR 98.10 - Other importations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... EMBRYOS AND ANIMAL SEMEN Ruminant and Swine Embryos from Regions Free of Rinderpest and Foot-and-Mouth Disease; and Embryos of Horses and Asses § 98.10 Other importations. Notwithstanding other provisions in... States of embryos other than as provided for in this part under such conditions as the Administrator may...

  3. 9 CFR 98.10 - Other importations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... EMBRYOS AND ANIMAL SEMEN Ruminant and Swine Embryos from Regions Free of Rinderpest and Foot-and-Mouth Disease; and Embryos of Horses and Asses § 98.10 Other importations. Notwithstanding other provisions in... States of embryos other than as provided for in this part under such conditions as the Administrator may...

  4. 9 CFR 98.10 - Other importations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... EMBRYOS AND ANIMAL SEMEN Ruminant and Swine Embryos from Regions Free of Rinderpest and Foot-and-Mouth Disease; and Embryos of Horses and Asses § 98.10 Other importations. Notwithstanding other provisions in... States of embryos other than as provided for in this part under such conditions as the Administrator may...

  5. 9 CFR 98.10 - Other importations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... EMBRYOS AND ANIMAL SEMEN Ruminant and Swine Embryos from Regions Free of Rinderpest and Foot-and-Mouth Disease; and Embryos of Horses and Asses § 98.10 Other importations. Notwithstanding other provisions in... States of embryos other than as provided for in this part under such conditions as the Administrator may...

  6. 9 CFR 50.14 - Claims not allowed.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS... tuberculosis will not be allowed in any of the following cases: (a) The claimant has failed to comply with any... in the claimant's herd have not been tested for tuberculosis under APHIS or State supervision...

  7. 9 CFR 50.14 - Claims not allowed.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS... tuberculosis will not be allowed in any of the following cases: (a) The claimant has failed to comply with any... in the claimant's herd have not been tested for tuberculosis under APHIS or State supervision...

  8. 9 CFR 50.14 - Claims not allowed.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS... tuberculosis will not be allowed in any of the following cases: (a) The claimant has failed to comply with any... in the claimant's herd have not been tested for tuberculosis under APHIS or State supervision...

  9. 9 CFR 50.14 - Claims not allowed.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... COOPERATIVE CONTROL AND ERADICATION OF LIVESTOCK OR POULTRY DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS... tuberculosis will not be allowed in any of the following cases: (a) The claimant has failed to comply with any... in the claimant's herd have not been tested for tuberculosis under APHIS or State supervision...

  10. Mite Infestations of Man Contracted from Dogs and Cats

    PubMed Central

    Thomsett, L. R.

    1968-01-01

    Acarine infestations of the dog and cat are transmissible to man. The relation between age incidence in the host, duration of disease, and circumstances under which the animal is kept are stated. Fifty out of 65 human contacts at risk to 42 infected dogs and cats showed lesions of mite infestation; 48% of these lesions were confined to the arms and torso. It is important to consider animal mite infestation in the differential diagnosis of human pruritic and papular skin disease. ImagesFig. 1 PMID:4969550

  11. Differences between amyloid-β aggregation in solution and on the membrane: insights into elucidation of the mechanistic details of Alzheimer's disease.

    PubMed

    Kotler, Samuel A; Walsh, Patrick; Brender, Jeffrey R; Ramamoorthy, Ayyalusamy

    2014-10-07

    The association of the amyloid-β (Aβ) peptide with cellular membranes is hypothesized to be the underlying phenomenon of neurotoxicity in Alzheimer's disease. Misfolding of proteins and peptides, as is the case with Aβ, follows a progression from a monomeric state, through intermediates, ending at long, unbranched amyloid fibers. This tutorial review offers a perspective on the association of toxic Aβ structures with membranes as well as details of membrane-associated mechanisms of toxicity.

  12. Protons -- The Future of Radiation Therapy?

    NASA Astrophysics Data System (ADS)

    Avery, Steven

    2007-03-01

    Cancer is the 2^nd highest cause of death in the United States. The challenges of controlling this disease remain more difficult as the population lives longer. Proton therapy offers another choice in the management of cancer care. Proton therapy has existed since the late 1950s and the first hospital based center in the United States opened in 1990. Since that time four hospital based proton centers are treating patients with other centers either under construction or under consideration. This talk will focus on an introduction to proton therapy: it's medical advantages over current treatment modalities, accelerators and beam delivery systems, applications to clinical radiation oncology and the future outlook for proton therapy.

  13. Identifying low pH active and lactate-utilizing taxa within oral microbiome communities from healthy children using stable isotope probing techniques.

    PubMed

    McLean, Jeffrey S; Fansler, Sarah J; Majors, Paul D; McAteer, Kathleen; Allen, Lisa Z; Shirtliff, Mark E; Lux, Renate; Shi, Wenyuan

    2012-01-01

    Many human microbial infectious diseases including dental caries are polymicrobial in nature. How these complex multi-species communities evolve from a healthy to a diseased state is not well understood. Although many health- or disease-associated oral bacteria have been characterized in vitro, their physiology within the complex oral microbiome is difficult to determine with current approaches. In addition, about half of these species remain uncultivated to date with little known besides their 16S rRNA sequence. Lacking culture-based physiological analyses, the functional roles of uncultivated species will remain enigmatic despite their apparent disease correlation. To start addressing these knowledge gaps, we applied a combination of Magnetic Resonance Spectroscopy (MRS) with RNA and DNA based Stable Isotope Probing (SIP) to oral plaque communities from healthy children for in vitro temporal monitoring of metabolites and identification of metabolically active and inactive bacterial species. Supragingival plaque samples from caries-free children incubated with (13)C-substrates under imposed healthy (buffered, pH 7) and diseased states (pH 5.5 and pH 4.5) produced lactate as the dominant organic acid from glucose metabolism. Rapid lactate utilization upon glucose depletion was observed under pH 7 conditions. SIP analyses revealed a number of genera containing cultured and uncultivated taxa with metabolic capabilities at pH 5.5. The diversity of active species decreased significantly at pH 4.5 and was dominated by Lactobacillus and Propionibacterium species, both of which have been previously found within carious lesions from children. Our approach allowed for identification of species that metabolize carbohydrates under different pH conditions and supports the importance of Lactobacilli and Propionibacterium in the development of childhood caries. Identification of species within healthy subjects that are active at low pH can lead to a better understanding of oral caries onset and generate appropriate targets for preventative measures in the early stages.

  14. Resistance Begins with the First Foreign Footstep: China and Nicaragua

    DTIC Science & Technology

    2013-03-01

    arose in León and Granada . The rebels in León rallied under a former Zelayista, Benjamin Zeledón, while a recently ousted leader of the 17...coalition, Luis Mena, led the forces in Granada . While the United States entered the conflict under the auspices of neutrality, its actions clearly...arriving in Granada , Butler discovered that Mena suffered from a debilitating disease and had lost the will to fight. In exchange for safe passage

  15. The public health information infrastructure. A national review of the law on health information privacy.

    PubMed

    Gostin, L O; Lazzarini, Z; Neslund, V S; Osterholm, M T

    1996-06-26

    Our objectives were to review and analyze the laws in the 50 states, the District of Columbia, and Puerto Rico that regulate the acquisition, storage, and use of public health data and to offer proposals for reform of the laws on public health information privacy. Virtually all states reported some statutory protection for governmentally maintained health data for public health information in general (49 states), communicable diseases (42 states), and sexually transmitted diseases (43 states). State statutes permitted disclosure of data for statistical purposes (42 states), contact tracing (39 states), epidemiologic investigations (22 states), and subpoena or court order (14 states). The survey revealed significant problems that affect both the development of fair and effective public health information systems and the protection of privacy. Statutes may be silent about the degree of privacy protection afforded, confer weaker privacy protection to certain kinds of information, or grant health officials broad discretion to disseminate personal information. Our proposals for law reform are based on a meeting of experts at the Carter Presidential Center under the auspices of the Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists: (1) an independent data protection commission should be established, (2) health authorities should justify the collection of personally identifiable information, (3) subjects should be given basic information about data practices, (4) data should be held and used in accordance with fair information practices, (5) legally binding privacy and security assurances should attach to identifiable health information with significant penalties for breach of these assurances, (6) disclosure of data should be made only for purposes consistent with the original collection, and (7) secondary uses beyond those originally intended by the data collector should be permitted only with informed consent.

  16. Chronic Lyme disease: misconceptions and challenges for patient management

    PubMed Central

    Halperin, John J

    2015-01-01

    Lyme disease, infection with the tick-borne spirochete Borrelia burgdorferi, causes both specific and nonspecific symptoms. In untreated chronic infection, specific manifestations such as a relapsing large-joint oligoarthritis can persist for years, yet subside with appropriate antimicrobial therapy. Nervous system involvement occurs in 10%–15% of untreated patients and typically involves lymphocytic meningitis, cranial neuritis, and/or mononeuritis multiplex; in some rare cases, patients have parenchymal inflammation in the brain or spinal cord. Nervous system infection is similarly highly responsive to antimicrobial therapy, including oral doxycycline. Nonspecific symptoms such as fatigue, perceived cognitive slowing, headache, and others occur in patients with Lyme disease and are indistinguishable from comparable symptoms occurring in innumerable other inflammatory states. There is no evidence that these nonspecific symptoms reflect nervous system infection or damage, or that they are in any way specific to or diagnostic of this or other tick-borne infections. When these symptoms occur in patients with Lyme disease, they typically also subside after antimicrobial treatment, although this may take time. Chronic fatigue states have been reported to occur following any number of infections, including Lyme disease. The mechanism underlying this association is unclear, although there is no evidence in any of these infections that these chronic posttreatment symptoms are attributable to ongoing infection with B. burgdorferi or any other identified organism. Available appropriately controlled studies indicate that additional or prolonged courses of antimicrobial therapy do not benefit patients with a chronic fatigue-like state after appropriately treated Lyme disease. PMID:26028977

  17. Prevalence and associated features of self-reported freezing of gait in Parkinson disease: The DEEP FOG study.

    PubMed

    Amboni, M; Stocchi, F; Abbruzzese, G; Morgante, L; Onofrj, M; Ruggieri, S; Tinazzi, M; Zappia, M; Attar, M; Colombo, D; Simoni, L; Ori, A; Barone, P; Antonini, A

    2015-06-01

    Freezing of Gait (FOG) is a common and disabling symptom in patients with Parkinson disease (PD). The relationship between FOG and dopaminergic medication is complex. The aim of the present study was to estimate the prevalence of self-reported FOG, its associated clinical features, and its relationship with wearing-off in a wide PD population. This is an observational multicenter study of 634 consecutive non-demented PD patients. Patients were identified either as freezers or non-freezers based on item-3 of the Freezing of Gait-Questionnaire. FOG was then classified as on, off and onoff freezing based on its relationship with wearing-off. Patients were assessed with Unified Parkinson's Disease Rating Scale, Hoehn and Yahr scale, 8-item Parkinson's disease Questionnaire, Mini-Mental State Examination. Data from 593 patients were analyzed, 325 (54.3%) were freezers of whom 200 (61.6%) experienced FOG only during off state (off-freezers), 6 (1.8%) only during on state and 119 (36.6%) either in on and off states or independently of dopaminergic response-related symptoms (onoff-freezers). Overall, freezers vs non-freezers had longer disease duration, more advanced disease and greater disability. Moreover, freezers more frequently reported wearing-off and experienced worse quality of life. Onoff-freezers vs off-freezers were older, more severely disabled, less likely to experience wearing-off, treated with lower levodopa equivalent daily dose and with poorer cognitive performance. Self-reported FOG is mainly recognizable in advanced PD and is associated with more disability and worse quality of life. Onoff-FOG may represent the result of under-treatment or rather interpretable as a distinct clinical entity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. 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

  19. Physical activity and exercise attenuate neuroinflammation in neurological diseases.

    PubMed

    Spielman, Lindsay Joy; Little, Jonathan Peter; Klegeris, Andis

    2016-07-01

    Major depressive disorder (MDD), schizophrenia (SCH), Alzheimer's disease (AD), and Parkinson's disease (PD) are devastating neurological disorders, which increasingly contribute to global morbidity and mortality. Although the pathogenic mechanisms of these conditions are quite diverse, chronic neuroinflammation is one underlying feature shared by all these diseases. Even though the specific root causes of these diseases remain to be identified, evidence indicates that the observed neuroinflammation is initiated by unique pathological features associated with each specific disease. If the initial acute inflammation is not resolved, a chronic neuroinflammatory state develops and ultimately contributes to disease progression. Chronic neuroinflammation is characterized by adverse and non-specific activation of glial cells, which can lead to collateral damage of nearby neurons and other glia. This misdirected neuroinflammatory response is hypothesized to contribute to neuropathology in MDD, SCH, AD, and PD. Physical activity (PA), which is critical for maintenance of whole body and brain health, may also beneficially modify neuroimmune responses. Since PA has neuroimmune-modifying properties, and the common underlying feature of MDD, SCH, AD, and PD is chronic neuroinflammation, we hypothesize that PA could minimize brain diseases by modifying glia-mediated neuroinflammation. This review highlights current evidence supporting the disease-altering potential of PA and exercise through modifications of neuroimmune responses, specifically in MDD, SCH, AD and PD. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Quantifying the underlying landscape and paths of cancer

    PubMed Central

    Li, Chunhe; Wang, Jin

    2014-01-01

    Cancer is a disease regulated by the underlying gene networks. The emergence of normal and cancer states as well as the transformation between them can be thought of as a result of the gene network interactions and associated changes. We developed a global potential landscape and path framework to quantify cancer and associated processes. We constructed a cancer gene regulatory network based on the experimental evidences and uncovered the underlying landscape. The resulting tristable landscape characterizes important biological states: normal, cancer and apoptosis. The landscape topography in terms of barrier heights between stable state attractors quantifies the global stability of the cancer network system. We propose two mechanisms of cancerization: one is by the changes of landscape topography through the changes in regulation strengths of the gene networks. The other is by the fluctuations that help the system to go over the critical barrier at fixed landscape topography. The kinetic paths from least action principle quantify the transition processes among normal state, cancer state and apoptosis state. The kinetic rates provide the quantification of transition speeds among normal, cancer and apoptosis attractors. By the global sensitivity analysis of the gene network parameters on the landscape topography, we uncovered some key gene regulations determining the transitions between cancer and normal states. This can be used to guide the design of new anti-cancer tactics, through cocktail strategy of targeting multiple key regulation links simultaneously, for preventing cancer occurrence or transforming the early cancer state back to normal state. PMID:25232051

  1. Neoehrlichiosis: an emerging tick-borne zoonosis caused by Candidatus Neoehrlichia mikurensis.

    PubMed

    Silaghi, Cornelia; Beck, Relja; Oteo, José A; Pfeffer, Martin; Sprong, Hein

    2016-03-01

    Candidatus Neoehrlichia mikurensis is an emerging tick-borne pathogen causing a systemic inflammatory syndrome mostly in persons with underlying hematologic or autoimmune diseases. As it is neither well-known nor well-recognized, it might be misdiagnosed as recurrence of the underlying disease or as an unrelated arteriosclerotic vascular event. The pathogen is transmitted by hard ticks of the genus Ixodes and is closely associated with rodents in which transplacental transmission occurs. Transovarial transmission in ticks has not yet been shown. Infection rates vary greatly in ticks and rodents, but the causes for its spatiotemporal variations are largely unknown. This review summarizes the current state of knowledge on the geographical distribution and clinical importance of Ca. N. mikurensis. By elucidating the life history traits of this pathogen and determining more accurately its incidence in the human population, a better assessment of its public health relevance can be made. Most urgent research needs are the in vitro-cultivation of the pathogen, the development of specific serological tests, the determination of the full genomic sequence, the routine implementation of molecular diagnosis in diseased patients with a particular panel of underlying diseases, and promoting the knowledge about neoehrlichiosis among general practitioners, hospital physicians and the risk groups such as forest workers or immune-compromised people to raise awareness about this disease that can easily be treated when correctly diagnosed.

  2. Quantitation of Hydrogen Peroxide Fluctuations and Their Modulation of Dopamine Dynamics in the Rat Dorsal Striatum Using Fast-Scan Cyclic Voltammetry

    PubMed Central

    2013-01-01

    The dopaminergic neurons of the nigrostriatal dopamine (DA) projection from the substantia nigra to the dorsal striatum become dysfunctional and slowly degenerate in Parkinson’s disease, a neurodegenerative disorder that afflicts more than one million Americans. There is no specific known cause for idiopathic Parkinson’s disease; however, multiple lines of evidence implicate oxidative stress as an underlying factor in both the initiation and progression of the disease. This involves the enhanced generation of reactive oxygen species, including hydrogen peroxide (H2O2), whose role in complex biological processes is not well understood. Using fast-scan cyclic voltammetry at bare carbon-fiber microelectrodes, we have simultaneously monitored and quantified H2O2 and DA fluctuations in intact striatal tissue under basal conditions and in response to the initiation of oxidative stress. Furthermore, we have assessed the effect of acute increases in local H2O2 concentration on both electrically evoked DA release and basal DA levels. Increases in endogenous H2O2 in the dorsal striatum attenuated electrically evoked DA release, and also decreased basal DA levels in this brain region. These novel results will help to disambiguate the chemical mechanisms underlying the progression of neurodegenerative disease states, such as Parkinson’s disease, that involve oxidative stress. PMID:23556461

  3. Women's Health and Lung Development and Disease.

    PubMed

    Kocurek, Emily G; Hemnes, Anna R

    2016-06-01

    Although the lung is not traditionally thought of as an organ affected by sex-based differences, emerging literature elucidates major differences between men and women in the development, physiology, and predilection to and outcomes in lung diseases. These differences are driven by both differences in sex hormones and differences in environmental exposures. However, in many cases the underlying etiology of these sex- and gender-based differences is unknown. This article outlines the state-of-the-art knowledge on the etiology of sex differences in lung disease, including differences in lung development and physiology, and reviews therapy recommendations that are sex based. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Endocrinology Meets Metabolomics: Achievements, Pitfalls, and Challenges.

    PubMed

    Tokarz, Janina; Haid, Mark; Cecil, Alexander; Prehn, Cornelia; Artati, Anna; Möller, Gabriele; Adamski, Jerzy

    2017-10-01

    The metabolome, although very dynamic, is sufficiently stable to provide specific quantitative traits related to health and disease. Metabolomics requires balanced use of state-of-the-art study design, chemical analytics, biostatistics, and bioinformatics to deliver meaningful answers to contemporary questions in human disease research. The technology is now frequently employed for biomarker discovery and for elucidating the mechanisms underlying endocrine-related diseases. Metabolomics has also enriched genome-wide association studies (GWAS) in this area by providing functional data. The contributions of rare genetic variants to metabolome variance and to the human phenotype have been underestimated until now. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Health equality, social justice and the poverty of autonomy.

    PubMed

    Newdick, Christopher

    2017-10-01

    How does the concept of autonomy assist public responses to 'lifestyle' diseases? Autonomy is fundamental to bioethics, but its emphasis on self-determination and individuality hardly supports public health policies to eat and drink less and take more exercise. Autonomy rejects a 'nanny' state. Yet, the cost of non-communicable diseases is increasing to individuals personally and to public health systems generally. Health care systems are under mounting and unsustainable pressure. What is the proper responsibility of individuals, governments and corporate interests working within a global trading environment? When public health care resources are unlikely to increase, we cannot afford to be so diffident to the cost of avoidable diseases.

  6. Developmental Programming, a Pathway to Disease

    PubMed Central

    Cardoso, Rodolfo C.; Puttabyatappa, Muraly

    2016-01-01

    Accumulating evidence suggests that insults occurring during the perinatal period alter the developmental trajectory of the fetus/offspring leading to long-term detrimental outcomes that often culminate in adult pathologies. These perinatal insults include maternal/fetal disease states, nutritional deficits/excess, stress, lifestyle choices, exposure to environmental chemicals, and medical interventions. In addition to reviewing the various insults that contribute to developmental programming and the benefits of animal models in addressing underlying mechanisms, this review focuses on the commonalities in disease outcomes stemming from various insults, the convergence of mechanistic pathways via which various insults can lead to common outcomes, and identifies the knowledge gaps in the field and future directions. PMID:26859334

  7. The Immune System: Basis of so much Health and Disease: 4. Immunocytes.

    PubMed

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-05-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covers cells of the immune system (immunocytes). Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  8. Effects of noise on a computational model for disease states of mood disorders

    NASA Astrophysics Data System (ADS)

    Tobias Huber, Martin; Krieg, Jürgen-Christian; Braun, Hans Albert; Moss, Frank

    2000-03-01

    Nonlinear dynamics are currently proposed to explain the progressive course of recurrent mood disorders starting with isolated episodes and ending with accelerated irregular (``chaotic") mood fluctuations. Such a low-dimensional disease model is attractive because of its principal accordance with biological disease models, i.e. the kindling and biological rhythms model. However, most natural systems are nonlinear and noisy and several studies in the neuro- and physical sciences have demonstrated interesting cooperative behaviors arising from interacting random and deterministic dynamics. Here, we consider the effects of noise on a recent neurodynamical model for the timecourse of affective disorders (Huber et al.: Biological Psychiatry 1999;46:256-262). We describe noise effects on temporal patterns and mean episode frequencies of various in computo disease states. Our simulations demonstrate that noise can cause unstructured randomness or can maximize periodic order. The frequency of episode occurence can increase with noise but it can also remain unaffected or even can decrease. We show further that noise can make visible bifurcations before they would normally occur under deterministic conditions and we quantify this behavior with a recently developed statistical method. All these effects depend critically on both, the dynamic state and the noise intensity. Implications for neurobiology and course of mood disorders are discussed.

  9. [Hansen's disease in the northern region of Brazil--1986].

    PubMed

    Britto, R da S

    1989-12-01

    Some general facts about Hansen's Disease are presented: in the world, in the Americas, in 1986, with the purpose to focalize on the Northern Region of Brazil (Amazon Valley) where an attempt is made to specify, State, the clinical forms in the active registry, the respective coefficients of Prevalence, about the cases detected during the year, by clinical forms and the correspondent Coefficient of Incidence, the age range of less than 15 years, and above 15 years; and to analyze according to the township in the State of Amazonas in a series of 8 years, from 1979 to 1986, the registered cases under control and also without control, the new cases, by clinical form and Coefficient of Incidence, the positive cases among students in the capital and also in the country, and with more details, still by township and by Public Health Registry, in 1986, with the population, new cases, and Coefficient of Incidence, cases of the active registry, cases under control, Coefficient of Incidence, the relationship between patients/inhabitants, cases according to the decreasing intensity as far as the Prevalence and Health Department Regions: all this to give an idea, in detail, inclusive statistics, of the real position of Hansen's Disease in the Northern Region (Amazon Valley), with the highest figures of Prevalence and even of Incidence, in comparison with other Regions of the country, and to stress the grave situation of the endemic proportions of the disease, in Brazil in general and in that Regions, in particular.

  10. Spatially-Explicit Simulation Modeling of Ecological Response to Climate Change: Methodological Considerations in Predicting Shifting Population Dynamics of Infectious Disease Vectors.

    PubMed

    Dhingra, Radhika; Jimenez, Violeta; Chang, Howard H; Gambhir, Manoj; Fu, Joshua S; Liu, Yang; Remais, Justin V

    2013-09-01

    Poikilothermic disease vectors can respond to altered climates through spatial changes in both population size and phenology. Quantitative descriptors to characterize, analyze and visualize these dynamic responses are lacking, particularly across large spatial domains. In order to demonstrate the value of a spatially explicit, dynamic modeling approach, we assessed spatial changes in the population dynamics of Ixodes scapularis , the Lyme disease vector, using a temperature-forced population model simulated across a grid of 4 × 4 km cells covering the eastern United States, using both modeled (Weather Research and Forecasting (WRF) 3.2.1) baseline/current (2001-2004) and projected (Representative Concentration Pathway (RCP) 4.5 and RCP 8.5; 2057-2059) climate data. Ten dynamic population features (DPFs) were derived from simulated populations and analyzed spatially to characterize the regional population response to current and future climate across the domain. Each DPF under the current climate was assessed for its ability to discriminate observed Lyme disease risk and known vector presence/absence, using data from the US Centers for Disease Control and Prevention. Peak vector population and month of peak vector population were the DPFs that performed best as predictors of current Lyme disease risk. When examined under baseline and projected climate scenarios, the spatial and temporal distributions of DPFs shift and the seasonal cycle of key questing life stages is compressed under some scenarios. Our results demonstrate the utility of spatial characterization, analysis and visualization of dynamic population responses-including altered phenology-of disease vectors to altered climate.

  11. Spatially-Explicit Simulation Modeling of Ecological Response to Climate Change: Methodological Considerations in Predicting Shifting Population Dynamics of Infectious Disease Vectors

    PubMed Central

    Dhingra, Radhika; Jimenez, Violeta; Chang, Howard H.; Gambhir, Manoj; Fu, Joshua S.; Liu, Yang; Remais, Justin V.

    2014-01-01

    Poikilothermic disease vectors can respond to altered climates through spatial changes in both population size and phenology. Quantitative descriptors to characterize, analyze and visualize these dynamic responses are lacking, particularly across large spatial domains. In order to demonstrate the value of a spatially explicit, dynamic modeling approach, we assessed spatial changes in the population dynamics of Ixodes scapularis, the Lyme disease vector, using a temperature-forced population model simulated across a grid of 4 × 4 km cells covering the eastern United States, using both modeled (Weather Research and Forecasting (WRF) 3.2.1) baseline/current (2001–2004) and projected (Representative Concentration Pathway (RCP) 4.5 and RCP 8.5; 2057–2059) climate data. Ten dynamic population features (DPFs) were derived from simulated populations and analyzed spatially to characterize the regional population response to current and future climate across the domain. Each DPF under the current climate was assessed for its ability to discriminate observed Lyme disease risk and known vector presence/absence, using data from the US Centers for Disease Control and Prevention. Peak vector population and month of peak vector population were the DPFs that performed best as predictors of current Lyme disease risk. When examined under baseline and projected climate scenarios, the spatial and temporal distributions of DPFs shift and the seasonal cycle of key questing life stages is compressed under some scenarios. Our results demonstrate the utility of spatial characterization, analysis and visualization of dynamic population responses—including altered phenology—of disease vectors to altered climate. PMID:24772388

  12. Exopolysaccharides favor the survival of Erwinia amylovora under copper stress through different strategies.

    PubMed

    Ordax, Mónica; Marco-Noales, Ester; López, María M; Biosca, Elena G

    2010-09-01

    Erwinia amylovora causes fire blight, a destructive disease of rosaceous plants very difficult to control. We demonstrated that copper, employed to control plant diseases, induces the "viable-but-nonculturable" (VBNC) state in E. amylovora. Moreover, it was previously reported that copper increases production of its main exopolysaccharide (EPS), amylovoran. In this work, the copper-complexing ability of amylovoran and levan, other major EPS of E. amylovora, was demonstrated. Following this, EPS-deficient mutants were used to determine the role of these EPSs in survival of this bacterium in AB mineral medium with copper, compared to their wild type strain and AB without copper. Total, viable and culturable counts of all strains were monitored for six months. With copper, a larger fraction of the viable population of EPS mutants entered into the VBNC state, and earlier than their wild type strain, showing the contribution of both EPSs to long-term survival in a culturable state. Further, we demonstrated that both EPSs can be used as carbon source by E. amylovora under deprivation conditions. Overall, these previously unreported functions of amylovoran and levan provide survival advantages for E. amylovora, which could contribute to its enhanced persistence in nature. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  13. Amyloid Formation by Human Carboxypeptidase D Transthyretin-like Domain under Physiological Conditions*

    PubMed Central

    Garcia-Pardo, Javier; Graña-Montes, Ricardo; Fernandez-Mendez, Marc; Ruyra, Angels; Roher, Nerea; Aviles, Francesc X.; Lorenzo, Julia; Ventura, Salvador

    2014-01-01

    Protein aggregation is linked to a growing list of diseases, but it is also an intrinsic property of polypeptides, because the formation of functional globular proteins comes at the expense of an inherent aggregation propensity. Certain proteins can access aggregation-prone states from native-like conformations without the need to cross the energy barrier for unfolding. This is the case of transthyretin (TTR), a homotetrameric protein whose dissociation into its monomers initiates the aggregation cascade. Domains with structural homology to TTR exist in a number of proteins, including the M14B subfamily carboxypeptidases. We show here that the monomeric transthyretin-like domain of human carboxypeptidase D aggregates under close to physiological conditions into amyloid structures, with the population of folded but aggregation-prone states being controlled by the conformational stability of the domain. We thus confirm that the TTR fold keeps a generic residual aggregation propensity upon folding, resulting from the presence of preformed amyloidogenic β-strands in the native state. These structural elements should serve for functional/structural purposes, because they have not been purged out by evolution, but at the same time they put proteins like carboxypeptidase D at risk of aggregation in biological environments and thus can potentially lead to deposition diseases. PMID:25294878

  14. New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo?

    PubMed

    Oder, Esther; Safo, Martin K; Abdulmalik, Osheiza; Kato, Gregory J

    2016-10-01

    The hallmark of sickle cell disease is the polymerization of sickle haemoglobin due to a point mutation in the β-globin gene (HBB). Under low oxygen saturation, sickle haemoglobin assumes the tense (T-state) deoxygenated conformation that can form polymers, leading to rigid erythrocytes with impaired blood vessel transit, compounded or initiated by adhesion of erythrocytes to endothelium, neutrophils and platelets. This process results in vessel occlusion and ischaemia, with consequent acute pain, chronic organ damage, morbidity and mortality. Pharmacological agents that stabilize the higher oxygen affinity relaxed state (R-state) and/or destabilize the lower oxygen affinity T-state of haemoglobin have the potential to delay the sickling of circulating red cells by slowing polymerization kinetics. Relevant classes of agents include aromatic aldehydes, thiol derivatives, isothiocyanates and acyl salicylates derivatives. The aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF) increases oxygen affinity of sickle haemoglobin and reduces hypoxia-induced sickling in vitro and protects sickle cell mice from effects of hypoxia. It has completed pre-clinical testing and has entered clinical trials as treatment for sickle cell disease. A related molecule, GBT440, has shown R-state stabilization and increased oxygen affinity in preclinical testing. Allosteric modifiers of haemoglobin as direct anti-sickling agents target the fundamental pathophysiological mechanism of sickle cell disease. © 2016 John Wiley & Sons Ltd.

  15. Validity of urinary monoamine assay sales under the “spot baseline urinary neurotransmitter testing marketing model”

    PubMed Central

    Hinz, Marty; Stein, Alvin; Uncini, Thomas

    2011-01-01

    Spot baseline urinary monoamine assays have been used in medicine for over 50 years as a screening test for monoamine-secreting tumors, such as pheochromocytoma and carcinoid syndrome. In these disease states, when the result of a spot baseline monoamine assay is above the specific value set by the laboratory, it is an indication to obtain a 24-hour urine sample to make a definitive diagnosis. There are no defined applications where spot baseline urinary monoamine assays can be used to diagnose disease or other states directly. No peer-reviewed published original research exists which demonstrates that these assays are valid in the treatment of individual patients in the clinical setting. Since 2001, urinary monoamine assay sales have been promoted for numerous applications under the “spot baseline urinary neurotransmitter testing marketing model”. There is no published peer-reviewed original research that defines the scientific foundation upon which the claims for these assays are made. On the contrary, several articles have been published that discredit various aspects of the model. To fill the void, this manuscript is a comprehensive review of the scientific foundation and claims put forth by laboratories selling urinary monoamine assays under the spot baseline urinary neurotransmitter testing marketing model. PMID:21912487

  16. Workforce strategies to improve children's oral health.

    PubMed

    Goodwin, Kristine

    2014-12-01

    (1) Tooth decay is the most common chronic disease for children. (2) As millions receive dental coverage under the Affordable Care Act, the demand for dental services is expected to strain the current workforce's ability to meet their needs. (3) States have adopted various workforce approaches to improve access to dental care for underserved populations.

  17. Effects of climate change on forest insect and disease outbreaks

    Treesearch

    David W. Williams; Robert P. Long; Philip M. Wargo; Andrew M. Liebhold

    2000-01-01

    General circulation models (GCMs) predict dramatic future changes in climate for the northeastern and north central United States under doubled carbon dioxide (CO2) levels (Hansen et al., 1984; Manabe and Wetherald, 1987; Wilson and Mitchell, 1987; Cubasch and Cess, 1990; Mitchell et al., 1990). January temperatures are projected to rise as much...

  18. A novel approach for assessing density and range-wide abundance of prairie dogs

    Treesearch

    Aaron N. Facka; Paulette L. Ford; Gary W. Roemer

    2008-01-01

    Habitat loss, introduced disease, and government-sponsored eradication programs have caused population declines in all 5 species of prairie dogs. Black-tailed prairie dogs (Cynomys ludovicianus) currently occupy only about 2% of an extensive geographic range (160 million hectares) and were recently considered for listing under the United States...

  19. Food safety concerns in the U.S. and research on Shiga Toxin-producing E. coli

    USDA-ARS?s Scientific Manuscript database

    In the U.S., there are several government agencies that deal with food safety. Under the Department of Health and Human Services, there are the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC). The CDC collaborates with state agencies, private organizatio...

  20. 7 CFR 2.22 - Under Secretary for Marketing and Regulatory Programs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....C. 7112 note) regarding the Consultative Group to Eliminate the Use of Child Labor and Forced Labor... related activities necessary to prevent, detect, control or eradicate foot-and-mouth disease and other... Act (7 U.S.C. 450) with respect to cooperation with States in control and eradication of plant and...

  1. Management of Bacterial Blight of Lilac Caused by Pseudomonas syringae by Growing Plants under Plastic Shelters

    USDA-ARS?s Scientific Manuscript database

    Pseudomonas syringae pv. syringae causes some of the most economically-important bacterial diseases affecting woody perennials grown by the nursery industry in the Pacific Northwest of the United States. In this study, we evaluated a cultural control practice, placement of plants in plastic shelter...

  2. Seroprevalence of viral and bacterial diseases among the bovines in Himachal Pradesh, India

    PubMed Central

    Katoch, Shailja; Dohru, Shweta; Sharma, Mandeep; Vashist, Vikram; Chahota, Rajesh; Dhar, Prasenjit; Thakur, Aneesh; Verma, Subhash

    2017-01-01

    Aim: The study was designed to measure the seroprevalence of viral and bacterial diseases: Infectious bovine rhinotracheitis, bovine viral diarrhea, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, brucellosis, and paratuberculosis among bovine of Himachal Pradesh during the year 2013-2015. Materials and Methods: The serum samples were collected from seven districts of state, namely, Bilaspur, Kangra, Kinnaur, Lahul and Spiti, Mandi, Sirmour, and Solan. The samples were screened using indirect ELISA kits to measure the seroprevalence of viral and bacterial diseases. Results: The overall seroprevalence of infectious bovine rhinotracheitis was 24.24%, bovine viral diarrhea 1.52%, bovine leukemia 9.09%, bovine parainfluenza 57.58%, bovine respiratory syncytial disease 50%, brucellosis 19.69%, and paratuberculosis 9.09% in Himachal Pradesh. The seroprevalence of bovine rhinotracheitis, bovine leukemia, bovine parainfluenza, bovine respiratory syncytial disease, and paratuberculosis in the state varied significantly (p<0.01) while was insignificant for bovine viral diarrhea and brucellosis (p>0.01). Multiple seropositivity has been observed in this study. Bovine parainfluenza virus 3 was observed commonly in mixed infection with almost all viruses and bacteria under study. Conclusion: The viral and bacterial diseases are prevalent in the seven districts of Himachal Pradesh investigated in the study. Therefore, appropriate management practices and routine vaccination programs should be adopted to reduce the prevalence of these diseases. PMID:29391682

  3. Detecting Disease Specific Pathway Substructures through an Integrated Systems Biology Approach

    PubMed Central

    Alaimo, Salvatore; Marceca, Gioacchino Paolo; Ferro, Alfredo; Pulvirenti, Alfredo

    2017-01-01

    In the era of network medicine, pathway analysis methods play a central role in the prediction of phenotype from high throughput experiments. In this paper, we present a network-based systems biology approach capable of extracting disease-perturbed subpathways within pathway networks in connection with expression data taken from The Cancer Genome Atlas (TCGA). Our system extends pathways with missing regulatory elements, such as microRNAs, and their interactions with genes. The framework enables the extraction, visualization, and analysis of statistically significant disease-specific subpathways through an easy to use web interface. Our analysis shows that the methodology is able to fill the gap in current techniques, allowing a more comprehensive analysis of the phenomena underlying disease states. PMID:29657291

  4. From state dissociation to status dissociatus.

    PubMed

    Antelmi, Elena; Ferri, Raffaele; Iranzo, Alex; Arnulf, Isabelle; Dauvilliers, Yves; Bhatia, Kailash P; Liguori, Rocco; Schenck, Carlos H; Plazzi, Giuseppe

    2016-08-01

    The states of being are conventionally defined by the simultaneous occurrence of behavioral, neurophysiological and autonomic descriptors. State dissociation disorders are due to the intrusion of features typical of a different state into an ongoing state. Disorders related to these conditions are classified according to the ongoing main state and comprise: 1) Dissociation from prevailing wakefulness as seen in hypnagogic or hypnopompic hallucinations, automatic behaviors, sleep drunkenness, cataplexy and sleep paralysis 2) Dissociation from rapid eye movement (REM) sleep as seen in REM sleep behavior disorder and lucid dreaming and 3) Dissociation from NREM sleep as seen in the disorders of arousal. The extreme expression of states dissociation is characterized by the asynchronous occurrence of the various components of the different states that prevents the recognition of any state of being. This condition has been named status dissociatus. According to the underlying disorders/diseases and to their severity, among status dissociatus we may recognize disorders in which such an extreme dissociation occurs only at night time or intermittently (i.e., autoimmune encephalopathies, narcolepsy type 1 and IgLON5 parasomnia), and others in which it occurs nearly continuously with complete loss of any conventionally defined state of being, and of the circadian pattern (agrypnia excitata). Here, we render a comprehensive review of all diseases/disorders associated with state dissociation and status dissociatus and propose a critical classification of this complex scenario. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Inferring pathological states in cortical neuron microcircuits.

    PubMed

    Rydzewski, Jakub; Nowak, Wieslaw; Nicosia, Giuseppe

    2015-12-07

    The brain activity is to a large extent determined by states of neural cortex microcircuits. Unfortunately, accuracy of results from neural circuits׳ mathematical models is often biased by the presence of uncertainties in underlying experimental data. Moreover, due to problems with uncertainties identification in a multidimensional parameters space, it is almost impossible to classify states of the neural cortex, which correspond to a particular set of the parameters. Here, we develop a complete methodology for determining uncertainties and the novel protocol for classifying all states in any neuroinformatic model. Further, we test this protocol on the mathematical, nonlinear model of such a microcircuit developed by Giugliano et al. (2008) and applied in the experimental data analysis of Huntington׳s disease. Up to now, the link between parameter domains in the mathematical model of Huntington׳s disease and the pathological states in cortical microcircuits has remained unclear. In this paper we precisely identify all the uncertainties, the most crucial input parameters and domains that drive the system into an unhealthy state. The scheme proposed here is general and can be easily applied to other mathematical models of biological phenomena. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Moderating effects of music on resting state networks.

    PubMed

    Kay, Benjamin P; Meng, Xiangxiang; Difrancesco, Mark W; Holland, Scott K; Szaflarski, Jerzy P

    2012-04-04

    Resting state networks (RSNs) are spontaneous, synchronous, low-frequency oscillations observed in the brains of subjects who are awake but at rest. A particular RSN called the default mode network (DMN) has been shown to exhibit changes associated with neurological disorders such as temporal lobe epilepsy or Alzheimer's disease. Previous studies have also found that differing experimental conditions such as eyes-open versus eyes-closed can produce measurable changes in the DMN. These condition-associated changes have the potential of confounding the measurements of changes in RSNs related to or caused by disease state(s). In this study, we use fMRI measurements of resting-state connectivity paired with EEG measurements of alpha rhythm and employ independent component analysis, undirected graphs of partial spectral coherence, and spatiotemporal regression to investigate the effect of music-listening on RSNs and the DMN in particular. We observed similar patterns of DMN connectivity in subjects who were listening to music compared with those who were not, with a trend toward a more introspective pattern of resting-state connectivity during music-listening. We conclude that music-listening is a valid condition under which the DMN can be studied. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Inverse probability weighting estimation of the volume under the ROC surface in the presence of verification bias.

    PubMed

    Zhang, Ying; Alonzo, Todd A

    2016-11-01

    In diagnostic medicine, the volume under the receiver operating characteristic (ROC) surface (VUS) is a commonly used index to quantify the ability of a continuous diagnostic test to discriminate between three disease states. In practice, verification of the true disease status may be performed only for a subset of subjects under study since the verification procedure is invasive, risky, or expensive. The selection for disease examination might depend on the results of the diagnostic test and other clinical characteristics of the patients, which in turn can cause bias in estimates of the VUS. This bias is referred to as verification bias. Existing verification bias correction in three-way ROC analysis focuses on ordinal tests. We propose verification bias-correction methods to construct ROC surface and estimate the VUS for a continuous diagnostic test, based on inverse probability weighting. By applying U-statistics theory, we develop asymptotic properties for the estimator. A Jackknife estimator of variance is also derived. Extensive simulation studies are performed to evaluate the performance of the new estimators in terms of bias correction and variance. The proposed methods are used to assess the ability of a biomarker to accurately identify stages of Alzheimer's disease. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. A longitudinal ecological study of seasonal influenza deaths in relation to climate conditions in the United States from 1999 through 2011.

    PubMed

    Geier, David A; Kern, Janet K; Geier, Mark R

    2018-01-01

    Introduction: Influenza is an acute respiratory disease with significant annual global morbidity/mortality. Influenza transmission occurs in distinct seasonal patterns suggesting an importance of climate conditions on disease pathogenesis. This hypothesis-testing study evaluated microenvironment conditions within different demographic/geographical groups on seasonal influenza deaths in the United States. Materials and methods: The United States Centers for Disease Control and Prevention (CDC) Wonder online computer interface was utilized to integrate and analyze potential correlations in data generated from 1999 through 2011 for climate conditions of mean daily sunlight (KJ/m 2 ), mean daily maximum air temperature ( o C), mean daily minimum air temperature ( o C), and mean daily precipitation (mm) from the North America Land Data Assimilation System (NLDAS) database and on influenza mortality (ICD-10 codes:J09, J10, or J11) from the Underlying Cause of Death database. Results and discussion: Significant inverse correlations between the climate conditions of temperature, sunlight, and precipitation and seasonal influenza death rate were observed. Similar effects were observed among males and females, but when the data were separated by race and urbanization status significant differences were observed. Conclusion: This study highlights key factors that can help shape public health policy to deal with seasonal influenza in the United States and beyond.

  9. Contemporary disease management in Quebec.

    PubMed

    Gogovor, Amédé; Savoie, Michelle; Moride, Yola; Krelenbaum, Marilyn; Montague, Terrence

    2008-01-01

    Health or disease management (DM) has emerged as a promising solution to improve the quality of healthcare and patient outcomes in a cost-efficient way. This solution is particularly relevant in the care of our increasing, and aging, patient populations with multiple chronic diseases. This article reviews the recent history and current status of DM in the province of Quebec and summarizes its evolving perspectives and future prospects. Most DM projects in Quebec have developed from a public-private partnership, and they have addressed several disease states. The results of completed programs confirmed the presence of care gaps--the differences between best and usual care in several disease states. They also identified process changes leading to improved practices and enhanced professional satisfaction among stakeholders. Priorities identified for further research include increased knowledge of the underlying causes of care gaps and greater concentration on the measurement of clinical, humanistic and fiscal outcomes and their causal links to DM structures and processes. Although still embryonic in Quebec and Canada, the available evidence suggests that DM partnerships are practical and functional vehicles to expedite knowledge creation and transfer in the care of whole populations of patients. Future projects offer the promise of updated knowledge and continuously improved care and outcomes.

  10. The mini mental state examination at the time of Alzheimer's disease and related disorders diagnosis, according to age, education, gender and place of residence: a cross-sectional study among the French National Alzheimer database.

    PubMed

    Pradier, Christian; Sakarovitch, Charlotte; Le Duff, Franck; Layese, Richard; Metelkina, Asya; Anthony, Sabine; Tifratene, Karim; Robert, Philippe

    2014-01-01

    was firstly to describe the MMSE (Mini-Mental State Examination) score upon initial diagnosis of Alzheimer's disease and related disorders among the French population, according to age. Secondly, education, gender and place of residence were studied as factors potentially associated with delayed Alzheimer's disease diagnosis. we conducted a cross sectional analysis of the French National Alzheimer database (BNA). Data from 2008 to 2012 were extracted. Patients were selected at the moment of their first diagnosis of AD (n = 39,451). The MMSE score at initial diagnosis dropped significantly with increasing age. The test score increased with the degree of educational background regardless of age. Gender and place of residence were significantly related to the MMSE score, women and persons living in medical institutions having lower MMSE scores under the age of 90 years and at all educational levels. Health care professionals should be aware of these risk factors in order to maximize chances of earliest possible diagnosis of Alzheimer's disease and related disorders.

  11. Quantum dot nanoprobe-based quantitative analysis for prostate cancer (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Kang, Benedict J.; Jang, Gun Hyuk; Park, Sungwook; Lee, Kwan Hyi

    2016-09-01

    Prostate cancer causes one of the leading cancer-related deaths among the Caucasian adult males in Europe and the United State of America. However, it has a high recovery rate indicating when a proper treatment is delivered to a patient. There are cases of over- or under-treatments which exacerbate the disease states indicating the importance of proper therapeutic approach depending on stage of the disease. Recognition of the unmet needs has raised a need for stratification of the disease. There have been attempts to stratify based on biomarker expression patterns in the course of disease progression. To closely observe the biomarker expression patterns, we propose the use of quantitative imaging method by using fabricated quantum dot-based nanoprobe to quantify biomarker expression on the surface of prostate cancer cells. To characterize the cell line and analyze the biomarker levels, cluster of differentiation 44 (CD 44), prostate specific membrane antigen (PSMA), and epithelial cell adhesion molecule (EpCAM) are used. Each selected biomarker per cell line has been quantified from which we established a signature of biomarkers of a prostate cancer cell line.

  12. Mining disease state converters for medical intervention of diseases.

    PubMed

    Dong, Guozhu; Duan, Lei; Tang, Changjie

    2010-02-01

    In applications such as gene therapy and drug design, a key goal is to convert the disease state of diseased objects from an undesirable state into a desirable one. Such conversions may be achieved by changing the values of some attributes of the objects. For example, in gene therapy one may convert cancerous cells to normal ones by changing some genes' expression level from low to high or from high to low. In this paper, we define the disease state conversion problem as the discovery of disease state converters; a disease state converter is a small set of attribute value changes that may change an object's disease state from undesirable into desirable. We consider two variants of this problem: personalized disease state converter mining mines disease state converters for a given individual patient with a given disease, and universal disease state converter mining mines disease state converters for all samples with a given disease. We propose a DSCMiner algorithm to discover small and highly effective disease state converters. Since real-life medical experiments on living diseased instances are expensive and time consuming, we use classifiers trained from the datasets of given diseases to evaluate the quality of discovered converter sets. The effectiveness of a disease state converter is measured by the percentage of objects that are successfully converted from undesirable state into desirable state as deemed by state-of-the-art classifiers. We use experiments to evaluate the effectiveness of our algorithm and to show its effectiveness. We also discuss possible research directions for extensions and improvements. We note that the disease state conversion problem also has applications in customer retention, criminal rehabilitation, and company turn-around, where the goal is to convert class membership of objects whose class is an undesirable class.

  13. Portal Vein Thrombosis

    PubMed Central

    Chawla, Yogesh K.; Bodh, Vijay

    2015-01-01

    Portal vein thrombosis is an important cause of portal hypertension. PVT occurs in association with cirrhosis or as a result of malignant invasion by hepatocellular carcinoma or even in the absence of associated liver disease. With the current research into its genesis, majority now have an underlying prothrombotic state detectable. Endothelial activation and stagnant portal blood flow also contribute to formation of the thrombus. Acute non-cirrhotic PVT, chronic PVT (EHPVO), and portal vein thrombosis in cirrhosis are the three main variants of portal vein thrombosis with varying etiological factors and variability in presentation and management. Procoagulant state should be actively investigated. Anticoagulation is the mainstay of therapy for acute non-cirrhotic PVT, with supporting evidence for its use in cirrhotic population as well. Chronic PVT (EHPVO) on the other hand requires the management of portal hypertension as such and with role for anticoagulation in the setting of underlying prothrombotic state, however data is awaited in those with no underlying prothrombotic states. TIPS and liver transplant may be feasible even in the setting of PVT however proper selection of candidates and type of surgery is warranted. Thrombolysis and thrombectomy have some role. TARE is a new modality for management of HCC with portal vein invasion. PMID:25941431

  14. A Multi-layered Quantitative In Vivo Expression Atlas of the Podocyte Unravels Kidney Disease Candidate Genes.

    PubMed

    Rinschen, Markus M; Gödel, Markus; Grahammer, Florian; Zschiedrich, Stefan; Helmstädter, Martin; Kretz, Oliver; Zarei, Mostafa; Braun, Daniela A; Dittrich, Sebastian; Pahmeyer, Caroline; Schroder, Patricia; Teetzen, Carolin; Gee, HeonYung; Daouk, Ghaleb; Pohl, Martin; Kuhn, Elisa; Schermer, Bernhard; Küttner, Victoria; Boerries, Melanie; Busch, Hauke; Schiffer, Mario; Bergmann, Carsten; Krüger, Marcus; Hildebrandt, Friedhelm; Dengjel, Joern; Benzing, Thomas; Huber, Tobias B

    2018-05-22

    Damage to and loss of glomerular podocytes has been identified as the culprit lesion in progressive kidney diseases. Here, we combine mass spectrometry-based proteomics with mRNA sequencing, bioinformatics, and hypothesis-driven studies to provide a comprehensive and quantitative map of mammalian podocytes that identifies unanticipated signaling pathways. Comparison of the in vivo datasets with proteomics data from podocyte cell cultures showed a limited value of available cell culture models. Moreover, in vivo stable isotope labeling by amino acids uncovered surprisingly rapid synthesis of mitochondrial proteins under steady-state conditions that was perturbed under autophagy-deficient, disease-susceptible conditions. Integration of acquired omics dimensions suggested FARP1 as a candidate essential for podocyte function, which could be substantiated by genetic analysis in humans and knockdown experiments in zebrafish. This work exemplifies how the integration of multi-omics datasets can identify a framework of cell-type-specific features relevant for organ health and disease. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Increased recognition of Powassan encephalitis in the United States, 1999-2005.

    PubMed

    Hinten, Steven R; Beckett, Geoffrey A; Gensheimer, Kathleen F; Pritchard, Elizabeth; Courtney, Thomas M; Sears, Stephen D; Woytowicz, John M; Preston, David G; Smith, Robert P; Rand, Peter W; Lacombe, Eleanor H; Holman, Mary S; Lubelczyk, Charles B; Kelso, Patsy Tassler; Beelen, Andrew P; Stobierski, Mary Grace; Sotir, Mark J; Wong, Susan; Ebel, Gregory; Kosoy, Olga; Piesman, Joseph; Campbell, Grant L; Marfin, Anthony A

    2008-12-01

    Powassan virus (POWV) disease is a rare human disease caused by a tick-borne encephalitis group flavivirus maintained in a transmission cycle between Ixodes cookei and other ixodid ticks and small and medium-sized mammals. During 1958-1998, only 27 POWV disease cases (mostly Powassan encephalitis) were reported from eastern Canada and the northeastern United States (average, 0.7 cases per year). During 1999-2005, nine cases (described herein) of serologically confirmed POWV disease were reported in the United States (average, 1.3 cases per year): four from Maine, two from New York, and one each from Michigan, Vermont, and Wisconsin. The Michigan and Wisconsin cases are the first ever reported from the north-central United States. Of these nine patients, 5 (56%) were men, the median age was 69 years (range: 25-91 years), and 6 (67%) had onset during May-July. All but one patient developed encephalitis with acute onset of profound muscle weakness, confusion, and other severe neurologic signs. In one case, no neurologic symptoms were present but the presence of pleocytosis, an elevated cerebrospinal fluid (CSF) protein concentration, and POWV-specific immunoglobulin M in CSF suggested neuroinvasion. All patients recovered from their acute disease, but most had long-term neurologic sequelae. Periresidential ecologic investigations were performed in three cases, including tests of local mammals and ticks for evidence of POWV infection. Woodchucks (Marmota monax), striped skunks (Mephitis mephitis), and a raccoon (Procyon lotor) collected at two of the Maine case-patients' residences had neutralizing antibody titers to POWV. I. cookei were found on woodchucks and skunks and questing in grassy areas of one of these residences; all were negative for POWV. Although POWV disease is rare, it is probably under-recognized, and it causes significant morbidity, and thus is an additional tick-borne emerging infectious disease entity. Because no vaccine or specific therapy is available, the basis of prevention is personal protection from ticks (or "tick hygiene") and reduced exposure to peridomestic wild mammals.

  16. [Moyamoya disease as a rare cause of ischaemic stroke--case report].

    PubMed

    Kułakowska, Alina; Kapica-Topczewska, Katarzyna; Borowik, Helena; Drozdowski, Wiesław

    2009-10-01

    Moyamoya disease is a rare, progressive disease of the vessels diagnosed according to characteristic abnormalities of brain arteries in the angiography. The incidence of moyamoya disease in Europe is lower than in Asia and its clinical course in European population is probably different from Asiatic (older age of onset and rare incidence of hemorrhagic strokes). Two young patients were diagnosed as moyamoya disease on the basis of clinical symptoms (ischaemic stroke) and results of brain vessels' angiography, which documented an occlusion of both internal carotid arteries above branching-off the ocular arteries in the first patient and stenosis of distal internal carotid arteries and proximal medial and anterior cerebral arteries in the second one. Both patients are under control of the Neurological Outpatient Department and their neurological state is stable. Despite that moyamoya disease is a rare cause of ischaemic stroke, it should be always considered as one of etiologic factors, especially in young patients.

  17. Castleman's Disease: From Basic Mechanisms to Molecular Therapeutics

    PubMed Central

    El-Osta, Hazem E.

    2011-01-01

    Castleman's disease is a rare lymphoproliferative disorder in which there has been recent progress in elucidating underlying mechanisms with potential therapeutic implications. Unicentric Castleman's disease is an indolent condition that is often treated with local approaches. In contrast, patients with multicentric Castleman's disease (MCD) have a less favorable prognosis and require systemic treatment. Cytotoxic chemotherapy, with its attendant risk for toxicity, has been widely used to treat MCD, with variable efficacy. The discovery of putative etiologic factors and targets in MCD, particularly human herpes virus 8, CD20, and interleukin (IL)-6, has been translated into the use of rituximab and anti–IL-6-based therapy, as well as antiviral agents. In this article, we review the current state of the art of our understanding of Castleman's disease and its treatment and we provide insight into future treatment strategies based on disease biology. PMID:21441298

  18. Summarizing techniques that combine three non-parametric scores to detect disease-associated 2-way SNP-SNP interactions.

    PubMed

    Sengupta Chattopadhyay, Amrita; Hsiao, Ching-Lin; Chang, Chien Ching; Lian, Ie-Bin; Fann, Cathy S J

    2014-01-01

    Identifying susceptibility genes that influence complex diseases is extremely difficult because loci often influence the disease state through genetic interactions. Numerous approaches to detect disease-associated SNP-SNP interactions have been developed, but none consistently generates high-quality results under different disease scenarios. Using summarizing techniques to combine a number of existing methods may provide a solution to this problem. Here we used three popular non-parametric methods-Gini, absolute probability difference (APD), and entropy-to develop two novel summary scores, namely principle component score (PCS) and Z-sum score (ZSS), with which to predict disease-associated genetic interactions. We used a simulation study to compare performance of the non-parametric scores, the summary scores, the scaled-sum score (SSS; used in polymorphism interaction analysis (PIA)), and the multifactor dimensionality reduction (MDR). The non-parametric methods achieved high power, but no non-parametric method outperformed all others under a variety of epistatic scenarios. PCS and ZSS, however, outperformed MDR. PCS, ZSS and SSS displayed controlled type-I-errors (<0.05) compared to GS, APDS, ES (>0.05). A real data study using the genetic-analysis-workshop 16 (GAW 16) rheumatoid arthritis dataset identified a number of interesting SNP-SNP interactions. © 2013 Elsevier B.V. All rights reserved.

  19. A whole-brain computational modeling approach to explain the alterations in resting-state functional connectivity during progression of Alzheimer's disease.

    PubMed

    Demirtaş, Murat; Falcon, Carles; Tucholka, Alan; Gispert, Juan Domingo; Molinuevo, José Luis; Deco, Gustavo

    2017-01-01

    Alzheimer's disease (AD) is the most common dementia with dramatic consequences. The research in structural and functional neuroimaging showed altered brain connectivity in AD. In this study, we investigated the whole-brain resting state functional connectivity (FC) of the subjects with preclinical Alzheimer's disease (PAD), mild cognitive impairment due to AD (MCI) and mild dementia due to Alzheimer's disease (AD), the impact of APOE4 carriership, as well as in relation to variations in core AD CSF biomarkers. The synchronization in the whole-brain was monotonously decreasing during the course of the disease progression. Furthermore, in AD patients we found widespread significant decreases in functional connectivity (FC) strengths particularly in the brain regions with high global connectivity. We employed a whole-brain computational modeling approach to study the mechanisms underlying these alterations. To characterize the causal interactions between brain regions, we estimated the effective connectivity (EC) in the model. We found that the significant EC differences in AD were primarily located in left temporal lobe. Then, we systematically manipulated the underlying dynamics of the model to investigate simulated changes in FC based on the healthy control subjects. Furthermore, we found distinct patterns involving CSF biomarkers of amyloid-beta (Aβ1 - 42) total tau (t-tau) and phosphorylated tau (p-tau). CSF Aβ1 - 42 was associated to the contrast between healthy control subjects and clinical groups. Nevertheless, tau CSF biomarkers were associated to the variability in whole-brain synchronization and sensory integration regions. These associations were robust across clinical groups, unlike the associations that were found for CSF Aβ1 - 42. APOE4 carriership showed no significant correlations with the connectivity measures.

  20. Decreased sodium:potassium ratios in cats: 49 cases.

    PubMed

    Bell, Rory; Mellor, Dominic J; Ramsey, Ian; Knottenbelt, Clare

    2005-06-01

    Sodium:potassium (Na:K) ratios are often reported in feline biochemical panels, although the importance of this measurement has not been investigated. The aims of this study were to document the range of feline disease states associated with a decreased Na:K ratio, to determine the prevalence of this biochemical abnormality in a referral hospital population, and to identify any particular disease that was more likely to have a decreased Na:K ratio. A group of 49 cats with decreased Na:K ratios was compared with a group of 50 cats with normal Na:K ratios that were randomly selected from the same hospital population. Twelve of the 49 cats (24.5%) had gastrointestinal disease, 10 (20.4%) had urinary disease, 8 (16.3%) had endocrine disease, 8 (16.3%) had cardiorespiratory disease, and 5 (10.0%) had diseases affecting other body systems. Six (12.2%) had artifactually decreased Na:K ratios. No cat was identified with hypoadrenocorticism. Statistical analysis revealed that, although none of these disease states was significantly over- or under-represented in the affected group, a significantly higher proportion of cats with decreased Na:K ratio had body cavity effusions (P = .025). Serum potassium concentrations were significantly higher in the affected group (P < .0001), but there was no significant difference in mean sodium concentration between the 2 groups. Decreased Na:K ratios frequently occur in cats with diseases other than hypoadrenocorticism, including cats with effusions. These findings should be considered when evaluating cats with this biochemical abnormality.

  1. Using administrative medical claims data to supplement state disease registry systems for reporting zoonotic infections.

    PubMed

    Jones, Stephen G; Coulter, Steven; Conner, William

    2013-01-01

    To determine what, if any, opportunity exists in using administrative medical claims data for supplemental reporting to the state infectious disease registry system. Cases of five tick-borne (Lyme disease (LD), babesiosis, ehrlichiosis, Rocky Mountain spotted fever (RMSF), tularemia) and two mosquito-borne diseases (West Nile virus, La Crosse viral encephalitis) reported to the Tennessee Department of Health during 2000-2009 were selected for study. Similarly, medically diagnosed cases from a Tennessee-based managed care organization (MCO) claims data warehouse were extracted for the same time period. MCO and Tennessee Department of Health incidence rates were compared using a complete randomized block design within a general linear mixed model to measure potential supplemental reporting opportunity. MCO LD incidence was 7.7 times higher (p<0.001) than that reported to the state, possibly indicating significant under-reporting (∼196 unreported cases per year). MCO data also suggest about 33 cases of RMSF go unreported each year in Tennessee (p<0.001). Three cases of babesiosis were discovered using claims data, a significant finding as this disease was only recently confirmed in Tennessee. Data sharing between MCOs and health departments for vaccine information already exists (eg, the Vaccine Safety Datalink Rapid Cycle Analysis project). There may be a significant opportunity in Tennessee to supplement the current passive infectious disease reporting system with administrative claims data, particularly for LD and RMSF. There are limitations with administrative claims data, but health plans may help bridge data gaps and support the federal administration's vision of combining public and private data into one source.

  2. Deaths: Leading Causes for 2012.

    PubMed

    Heron, Melonie

    2015-08-31

    This report presents final 2012 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2012," the National Center for Health Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2012. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2012, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). These causes accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2012 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  3. Deaths: leading causes for 2007.

    PubMed

    Heron, Melonie

    2011-08-26

    This report presents final 2007 data on the 10 leading causes of death in the United States by age, race, sex, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2007. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2007, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Cerebrovascular diseases; Chronic lower respiratory diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Septicemia. They accounted for approximately 76 percent of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2007 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  4. Deaths: leading causes for 2009.

    PubMed

    Heron, Melonie

    2012-10-26

    This report presents final 2009 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2009. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2009, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). These causes accounted for approximately 75% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2009 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  5. Deaths: leading causes for 2008.

    PubMed

    Heron, Melonie

    2012-06-06

    This report presents final 2008 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2008. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. in 2008, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for approximately 76 percent of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2008 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  6. Geographic distribution of dementia mortality: elevated mortality rates for black and white Americans by place of birth.

    PubMed

    Glymour, M Maria; Kosheleva, Anna; Wadley, Virginia G; Weiss, Christopher; Manly, Jennifer J

    2011-01-01

    We hypothesized that patterns of elevated stroke mortality among those born in the United States Stroke Belt (SB) states also prevailed for mortality related to all-cause dementia or Alzheimer Disease. Cause-specific mortality (contributing cause of death, including underlying cause cases) rates in 2000 for United States-born African Americans and whites aged 65 to 89 years were calculated by linking national mortality records with population data based on race, sex, age, and birth state or state of residence in 2000. Birth in a SB state (NC, SC, GA, TN, AR, MS, or AL) was cross-classified against SB residence at the 2000 Census. Compared with those who were not born in the SB, odds of all-cause dementia mortality were significantly elevated by 29% for African Americans and 19% for whites born in the SB. These patterns prevailed among individuals who no longer lived in the SB at death. Patterns were similar for Alzheimer Disease-related mortality. Some non-SB states were also associated with significant elevations in dementia-related mortality. Dementia mortality rates follow geographic patterns similar to stroke mortality, with elevated rates among those born in the SB. This suggests important roles for geographically patterned childhood exposures in establishing cognitive reserve.

  7. Undocumented Immigration, Drug Problems, and Driving Under the Influence in the United States, 1990-2014.

    PubMed

    Light, Michael T; Miller, Ty; Kelly, Brian C

    2017-09-01

    To examine the influence of undocumented immigration in the United States on 4 different metrics of drug and alcohol problems: drug arrests, drug overdose fatalities, driving under the influence (DUI) arrests, and DUI deaths. We combined newly developed state-level estimates of the undocumented population between 1990 and 2014 from the Center for Migration Studies with arrest data from the Federal Bureau of Investigation Uniform Crime Reports and fatality information from the Fatality Analysis Reporting System and the Centers for Disease Control and Prevention Underlying Cause of Death database. We used fixed-effects regression models to examine the longitudinal association between increased undocumented immigration and drug problems and drunk driving. Increased undocumented immigration was significantly associated with reductions in drug arrests, drug overdose deaths, and DUI arrests, net of other factors. There was no significant relationship between increased undocumented immigration and DUI deaths. This study provides evidence that undocumented immigration has not increased the prevalence of drug or alcohol problems, but may be associated with reductions in these public health concerns.

  8. Deaths: leading causes for 2005.

    PubMed

    Heron, Melonie; Tejada-Vera, Betzaida

    2009-12-23

    This report presents final 2005 data on the 10 leading causes of death in the United States by age, race, sex, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2005. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2005, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Cerebrovascular diseases; Chronic lower respiratory diseases; Accidents (unintentional injuries); Diabetes mellitus; Alzheimer's disease; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Septicemia. They accounted for about 77 percent of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2005 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birthweight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Newborn affected by complications of placenta, cord and membranes; Accidents (unintentional injuries); Respiratory distress of newborn; Bacterial sepsis of newborn; Neonatal hemorrhage; and Necrotizing enterocolitis of newborn. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods.

  9. Measuring underreporting and under-ascertainment in infectious disease datasets: a comparison of methods

    PubMed Central

    2014-01-01

    Background Efficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true’ incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting. Methods Within the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens. Results MFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-, country-, age-, and sex-specific. Conclusions When routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is necessary to adjust for underestimation. MFs can be used to adjust notification and surveillance data to provide more realistic estimates of incidence. PMID:24517715

  10. 38 CFR 3.816 - Awards under the Nehmer Court Orders for disability or death caused by a condition presumptively...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Court Orders for disability or death caused by a condition presumptively associated with herbicide... with herbicide exposure. (a) Purpose. This section states effective-date rules required by orders of a... member means: (i) A Vietnam veteran who has a covered herbicide disease; or (ii) A surviving spouse...

  11. 38 CFR 3.816 - Awards under the Nehmer Court Orders for disability or death caused by a condition presumptively...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Court Orders for disability or death caused by a condition presumptively associated with herbicide... with herbicide exposure. (a) Purpose. This section states effective-date rules required by orders of a... member means: (i) A Vietnam veteran who has a covered herbicide disease; or (ii) A surviving spouse...

  12. 38 CFR 3.816 - Awards under the Nehmer Court Orders for disability or death caused by a condition presumptively...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Court Orders for disability or death caused by a condition presumptively associated with herbicide... with herbicide exposure. (a) Purpose. This section states effective-date rules required by orders of a... member means: (i) A Vietnam veteran who has a covered herbicide disease; or (ii) A surviving spouse...

  13. 38 CFR 3.816 - Awards under the Nehmer Court Orders for disability or death caused by a condition presumptively...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Court Orders for disability or death caused by a condition presumptively associated with herbicide... with herbicide exposure. (a) Purpose. This section states effective-date rules required by orders of a... member means: (i) A Vietnam veteran who has a covered herbicide disease; or (ii) A surviving spouse...

  14. 38 CFR 3.816 - Awards under the Nehmer Court Orders for disability or death caused by a condition presumptively...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Court Orders for disability or death caused by a condition presumptively associated with herbicide... with herbicide exposure. (a) Purpose. This section states effective-date rules required by orders of a... member means: (i) A Vietnam veteran who has a covered herbicide disease; or (ii) A surviving spouse...

  15. Revisiting Tax Benefits for Parents of Children with Special Needs, Part 1

    ERIC Educational Resources Information Center

    Brinker, Thomas M., Jr.; Sherman, W. Richard; Ivers, James F., III

    2010-01-01

    The Center for Disease Control (CDC) estimates that up to 500,000 individuals under the age of 21 have autism, Asperger's syndrome, and other neurological disorders. These increasing numbers are already beginning to impact state and local governmentally funded programs as they face shortfalls, forcing parents to absorb more of their children's…

  16. 77 FR 1388 - Lists of Regions Classified With Respect to Certain Animal Diseases and States Approved To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-10

    ...'s stores, airplane meals, and baggage containing pork or pork products, other than those articles... specified regions. (a) The meat of ruminants or swine, and other animal products, and ship stores, airplane... all parts of the carcass of any ruminant or swine, other than meat and articles regulated under part...

  17. Perspectives on Systems Modeling of Human Peripheral Blood Mononuclear Cells

    PubMed Central

    Sen, Partho; Kemppainen, Esko; Orešič, Matej

    2018-01-01

    Human peripheral blood mononuclear cells (PBMCs) are the key drivers of the immune responses. These cells undergo activation, proliferation and differentiation into various subsets. During these processes they initiate metabolic reprogramming, which is coordinated by specific gene and protein activities. PBMCs as a model system have been widely used to study metabolic and autoimmune diseases. Herein we review various omics and systems-based approaches such as transcriptomics, epigenomics, proteomics, and metabolomics as applied to PBMCs, particularly T helper subsets, that unveiled disease markers and the underlying mechanisms. We also discuss and emphasize several aspects of T cell metabolic modeling in healthy and disease states using genome-scale metabolic models. PMID:29376056

  18. Report on the Symposium “Molecular Mechanisms Involved in Neurodegeneration”

    PubMed Central

    Pentón-Rol, Giselle; Cervantes-Llanos, Majel

    2018-01-01

    The prevalence of neurodegenerative diseases is currently a major concern in public health because of the lack of neuroprotective and neuroregenerative drugs. The symposium on Molecular Mechanisms Involved in Neurodegeneration held in Varadero, Cuba, updated the participants on the basic mechanisms of neurodegeneration, on the different approaches for drug discovery, and on early research results on therapeutic approaches for the treatment of neurodegenerative diseases. Alzheimer’s disease and in silico research were covered by many of the presentations in the symposium, under the umbrella of the “State of the Art of Non-clinical Models for Neurodegenerative Diseases” International Congress, held from 20 to 24 June 2017. This paper summarizes the highlights of the symposium. PMID:29346273

  19. Improving Value for Patients with Eczema.

    PubMed

    Block, Julie

    2018-04-01

    Chronic diseases now represent a cost majority in the United States health care system. Contributing factors to rising costs include expensive novel and emerging therapies, under-treatment of disease, under-management of comorbidities, and patient dissatisfaction with care results. Critical to identifying replicable improvement methods is a reliable model to measure value. If we understand value within healthcare consumerism to be equal to a patient's health outcome improvement over costs associated with care (Value=Outcomes/Costs), we can use this equation to measure the improvement of value. Research and literature show that patient activation-the skills and confidence that equip patients to become actively engaged in their health care-impact health outcomes, costs, and patient experience. Reaching patient activation through engagement methods including shared decision-making (SDM) lead to improved value of care received. The National Eczema Association (NEA) Shared Decision-Making Resource Center can be a transformative strategy to measure and evaluate value of health care interventions for eczema patients to advance a value-driven health care system in the United States. Through this Resource Center, NEA will measure patient value through their own perceptions using validated PRO instruments and other patient-generated health data. Assessment of this data will reveal findings that can assist researchers in evaluating the impact this care framework on patient-perceived value across other chronic diseases. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  20. Global occurrence of infant botulism, 1976-2006.

    PubMed

    Koepke, Ruth; Sobel, Jeremy; Arnon, Stephen S

    2008-07-01

    To summarize the worldwide occurrence of reported infant (intestinal toxemia) botulism cases since first recognition of the disease in 1976. We collected information on infant botulism cases by active and passive surveillance, by provision of therapeutic Human Botulism Immune Globulin to suspected cases, and by searching the medical literature. We defined a case as laboratory-confirmed botulism that occurred in an infant

  1. Effect of biodiversity changes in disease risk: exploring disease emergence in a plant-virus system.

    PubMed

    Pagán, Israel; González-Jara, Pablo; Moreno-Letelier, Alejandra; Rodelo-Urrego, Manuel; Fraile, Aurora; Piñero, Daniel; García-Arenal, Fernando

    2012-01-01

    The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk) is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect), and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect). Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin) under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species.

  2. Estimation of AUC or Partial AUC under Test-Result-Dependent Sampling.

    PubMed

    Wang, Xiaofei; Ma, Junling; George, Stephen; Zhou, Haibo

    2012-01-01

    The area under the ROC curve (AUC) and partial area under the ROC curve (pAUC) are summary measures used to assess the accuracy of a biomarker in discriminating true disease status. The standard sampling approach used in biomarker validation studies is often inefficient and costly, especially when ascertaining the true disease status is costly and invasive. To improve efficiency and reduce the cost of biomarker validation studies, we consider a test-result-dependent sampling (TDS) scheme, in which subject selection for determining the disease state is dependent on the result of a biomarker assay. We first estimate the test-result distribution using data arising from the TDS design. With the estimated empirical test-result distribution, we propose consistent nonparametric estimators for AUC and pAUC and establish the asymptotic properties of the proposed estimators. Simulation studies show that the proposed estimators have good finite sample properties and that the TDS design yields more efficient AUC and pAUC estimates than a simple random sampling (SRS) design. A data example based on an ongoing cancer clinical trial is provided to illustrate the TDS design and the proposed estimators. This work can find broad applications in design and analysis of biomarker validation studies.

  3. Systems Biology Approaches to the Study of Biological Networks Underlying Alzheimer's Disease: Role of miRNAs.

    PubMed

    Roth, Wera; Hecker, David; Fava, Eugenio

    2016-01-01

    MicroRNAs (miRNAs) are emerging as significant regulators of mRNA complexity in the human central nervous system (CNS) thereby controlling distinct gene expression profiles in a spatio-temporal manner during development, neuronal plasticity, aging and (age-related) neurodegeneration, including Alzheimer's disease (AD). Increasing effort is expended towards dissecting and deciphering the molecular and genetic mechanisms of neurobiological and pathological functions of these brain-enriched miRNAs. Along these lines, recent data pinpoint distinct miRNAs and miRNA networks being linked to APP splicing, processing and Aβ pathology (Lukiw et al., Front Genet 3:327, 2013), and furthermore, to the regulation of tau and its cellular subnetworks (Lau et al., EMBO Mol Med 5:1613, 2013), altogether underlying the onset and propagation of Alzheimer's disease. MicroRNA profiling studies in Alzheimer's disease suffer from poor consensus which is an acknowledged concern in the field, and constitutes one of the current technical challenges. Hence, a strong demand for experimental and computational systems biology approaches arises, to incorporate and integrate distinct levels of information and scientific knowledge into a complex system of miRNA networks in the context of the transcriptome, proteome and metabolome in a given cellular environment. Here, we will discuss the state-of-the-art technologies and computational approaches on hand that may lead to a deeper understanding of the complex biological networks underlying the pathogenesis of Alzheimer's disease.

  4. Drug Development for Metastasis Prevention.

    PubMed

    Fontebasso, Yari; Dubinett, Steven M

    2015-01-01

    Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors.

  5. Outcome based state budget allocation for diabetes prevention programs using multi-criteria optimization with robust weights.

    PubMed

    Mehrotra, Sanjay; Kim, Kibaek

    2011-12-01

    We consider the problem of outcomes based budget allocations to chronic disease prevention programs across the United States (US) to achieve greater geographical healthcare equity. We use Diabetes Prevention and Control Programs (DPCP) by the Center for Disease Control and Prevention (CDC) as an example. We present a multi-criteria robust weighted sum model for such multi-criteria decision making in a group decision setting. The principal component analysis and an inverse linear programming techniques are presented and used to study the actual 2009 budget allocation by CDC. Our results show that the CDC budget allocation process for the DPCPs is not likely model based. In our empirical study, the relative weights for different prevalence and comorbidity factors and the corresponding budgets obtained under different weight regions are discussed. Parametric analysis suggests that money should be allocated to states to promote diabetes education and to increase patient-healthcare provider interactions to reduce disparity across the US.

  6. 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.

  7. Comparing methods of measuring geographic patterns in temporal trends: an application to county-level heart disease mortality in the United States, 1973 to 2010.

    PubMed

    Vaughan, Adam S; Kramer, Michael R; Waller, Lance A; Schieb, Linda J; Greer, Sophia; Casper, Michele

    2015-05-01

    To demonstrate the implications of choosing analytical methods for quantifying spatiotemporal trends, we compare the assumptions, implementation, and outcomes of popular methods using county-level heart disease mortality in the United States between 1973 and 2010. We applied four regression-based approaches (joinpoint regression, both aspatial and spatial generalized linear mixed models, and Bayesian space-time model) and compared resulting inferences for geographic patterns of local estimates of annual percent change and associated uncertainty. The average local percent change in heart disease mortality from each method was -4.5%, with the Bayesian model having the smallest range of values. The associated uncertainty in percent change differed markedly across the methods, with the Bayesian space-time model producing the narrowest range of variance (0.0-0.8). The geographic pattern of percent change was consistent across methods with smaller declines in the South Central United States and larger declines in the Northeast and Midwest. However, the geographic patterns of uncertainty differed markedly between methods. The similarity of results, including geographic patterns, for magnitude of percent change across these methods validates the underlying spatial pattern of declines in heart disease mortality. However, marked differences in degree of uncertainty indicate that Bayesian modeling offers substantially more precise estimates. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. [Disease versus disorder. Medical and socio-environmental aspects of mental suffering].

    PubMed

    Heinz, A

    2015-01-01

    A disease concept should be broad enough to provide social protection for all subjects suffering from this malady but at the same time it needs to be narrow enough to avoid pathologization of behavior that is merely socially undesirable. From a medical perspective a"disease" is present if functions are impaired that are relevant for individual survival. In the field of psychiatry and psychotherapy, such medically relevant functions include the ability to be alert and fully oriented, to ascribe one's own intentions to oneself and to modulate affects according to the situation. Beyond such medically relevant symptoms of a disease, any clinically relevant dysfunction should also be harmful for the individual if a mental malady is to be diagnosed. One such harmful consequence of a disease can be that the person feels ill and suffers from this state, another negative consequence for the individual can be due to an impairment of activities of daily living and social participation. These harmful consequences of a disease are usually discussed under the heading of the"illness experience" and the"sickness aspect" of any disorder. Beyond mental maladies characterized by disease symptoms that are accompanied either by an illness experience or impaired activities of daily living and social participation (sickness), there are many states of human suffering which can be objectified and classified but do not constitute a disease in the medical sense and should more aptly be named a disorder.

  9. Medical marijuana and the developing role of the pharmacist.

    PubMed

    Seamon, Matthew J; Fass, Jennifer A; Maniscalco-Feichtl, Maria; Abu-Shraie, Nada A

    2007-05-15

    The pharmacology, therapeutic uses, safety, drug-drug interactions, and drug-disease interactions of medical marijuana are reviewed, and the legal issues related to its use and the implications of medical marijuana for the pharmacist are presented. Marijuana contains more than 460 active chemicals and over 60 unique cannabinoids. The legal landscape surrounding marijuana is surprisingly complex and unsettled. In the United States, 11 states and several municipalities have legalized medical marijuana. Another state provides legislation that allows patients to claim a defense of medical necessity. Nevertheless, patients using medical marijuana may never interact with a pharmacist. Marijuana is a Schedule I controlled substance and its use is illegal under federal law. Marijuana has a number of purported therapeutic uses with a broad range of supporting evidence. There are five general indications for medical marijuana: (1) severe nausea and vomiting associated with cancer chemotherapy or other causes, (2) weight loss associated with debilitating illnesses, including HIV infection and cancer, (3) spasticity secondary to neurologic diseases, such as multiple sclerosis, (4) pain syndromes, and (5) other uses, such as for glaucoma. Marijuana is associated with adverse psychiatric, cardiovascular, respiratory, and immunologic events. Moreover, marijuana may interact with a number of prescription drugs and concomitant disease states. Several states have legalized the use of marijuana for chronic and debilitating medication conditions. Pharmacists need to understand the complex legal framework surrounding this issue so that they can protect themselves and better serve their patients.

  10. Trends in the leading causes of death in the United States, 1970-2002.

    PubMed

    Jemal, Ahmedin; Ward, Elizabeth; Hao, Yongping; Thun, Michael

    2005-09-14

    The decrease in overall death rates in the United States may mask changes in death rates from specific conditions. To examine temporal trends in the age-standardized death rates and in the number of deaths from the 6 leading causes of death in the United States. Analyses of vital statistics data on mortality in the United States from 1970 to 2002. The age-standardized death rate and number of deaths (coded as underlying cause) from each of the 6 leading causes of death: heart disease, stroke, cancer, chronic obstructive pulmonary disease, accidents (ie, related to transportation [motor vehicle, other land vehicles, and water, air, and space] and not related to transportation [falls, fire, and accidental posioning]), and diabetes mellitus. The age-standardized death rate (per 100,000 per year) from all causes combined decreased from 1242 in 1970 to 845 in 2002. The largest percentage decreases were in death rates from stroke (63%), heart disease (52%), and accidents (41%). The largest absolute decreases in death rates were from heart disease (262 deaths per 100,000), stroke (96 deaths per 100,000), and accidents (26 deaths per 100,000).The death rate from all types of cancer combined increased between 1970 and 1990 and then decreased through 2002, yielding a net decline of 2.7%. In contrast, death rates doubled from chronic obstructive pulmonary disease over the entire time interval and increased by 45% for diabetes since 1987. Despite decreases in age-standardized death rates from 4 of the 6 leading causes of death, the absolute number of deaths from these conditions continues to increase, although these deaths occur at older ages. The absolute number of deaths and age at death continue to increase in the United States. These temporal trends have major implications for health care and health care costs in an aging population.

  11. Metabolic and vascular origins of the BOLD effect: Implications for imaging pathology and resting-state brain function.

    PubMed

    Mark, Clarisse I; Mazerolle, Erin L; Chen, J Jean

    2015-08-01

    The blood oxygenation level-dependent (BOLD) phenomenon has profoundly revolutionized neuroscience, with applications ranging from normal brain development and aging, to brain disorders and diseases. While the BOLD effect represents an invaluable tool to map brain function, it does not measure neural activity directly; rather, it reflects changes in blood oxygenation resulting from the relative balance between cerebral oxygen metabolism (through neural activity) and oxygen supply (through cerebral blood flow and volume). As such, there are cases in which BOLD signals might be dissociated from neural activity, leading to misleading results. The emphasis of this review is to develop a critical perspective for interpreting BOLD results, through a comprehensive consideration of BOLD's metabolic and vascular underpinnings. We demonstrate that such an understanding is especially important under disease or resting conditions. We also describe state-of-the-art acquisition and analytical techniques to reveal physiological information on the mechanisms underlying measured BOLD signals. With these goals in mind, this review is structured to provide a fundamental understanding of: 1) the physiological and physical sources of the BOLD contrast; 2) the extraction of information regarding oxidative metabolism and cerebrovascular reactivity from the BOLD signal, critical to investigating neuropathology; and 3) the fundamental importance of metabolic and vascular mechanisms for interpreting resting-state BOLD measurements. © 2015 Wiley Periodicals, Inc.

  12. State of the Art Review: Depression, Stress, Anxiety, and Cardiovascular Disease

    PubMed Central

    Edmondson, Donald; Kronish, Ian M.

    2015-01-01

    The notion that psychological states can influence physical health is hardly new, and perhaps nowhere has the mind-body connection been better studied than in cardiovascular disease (CVD). Recently, large prospective epidemiologic studies and smaller basic science studies have firmly established a connection between CVD and several psychological conditions, including depression, chronic psychological stress, posttraumatic stress disorder (PTSD), and anxiety. In addition, numerous clinical trials have been conducted to attempt to prevent or lessen the impact of these conditions on cardiovascular health. In this article, we review studies connecting depression, stress/PTSD, and anxiety to CVD, focusing on findings from the last 5 years. For each mental health condition, we first examine the epidemiologic evidence establishing a link with CVD. We then describe studies of potential underlying mechanisms and finally discuss treatment trials and directions for future research. PMID:25911639

  13. Medicalization, wish-fulfilling medicine, and disease mongering: toward a brave new world?

    PubMed

    Blasco-Fontecilla, H

    2014-03-01

    Western societies are characterized by a growing medicalization of life events, such as pregnancy, aging, or even death. Three concepts -medicalization, wish-fulfilling medicine, and disease mongering- are key in understanding the current practise of Medicine. Quite surprisingly, not a single study has addressed the relationship between all three of these concepts. The term medicalization expanded under the open-ended concept of health developed by the World Health Organization in 1946. One of the consequences of medicalization is the transition from patients to clients. Physicians are under increasing pressure to meet the insatiable demands of their clients. The term wish-fulfilling medicine refers to the increasing tendency of medicine to be used to fulfill personal wishes (i.e. enhanced work performance). The insatiable demand for healthcare is troublesome, particularly in Europe, where the welfare states are more and more under pressure. Finally, the term disease mongering refers to attempts by pharmaceutical companies to artificially enlarge their “markets” by convincing people that they suffer from some sickness and thus need medical treatment. Typical examples of disease mongering are social anxiety disorder, low bone mineral density, and premature ejaculation. Currently, some Public Health Services could be on the brink of collapse as they “navigate” between the scarce resources available and the users’ insatiable health demands. Therefore, it appears necessary to generate clear-cut Public Health Services Port-folios.

  14. Public health implications of changing rodent importation patterns— United States, 1999–2013

    PubMed Central

    Lankau, Emily W.; Sinclair, Julie R.; Schroeder, Betsy A.; Galland, G. Gale; Marano, Nina

    2015-01-01

    Summary The United States imports a large volume of live wild and domestic animal species; these animals pose a demonstrated risk for introduction of zoonotic diseases. Rodents are imported for multiple purposes, including scientific research, zoo exhibits, and the pet trade. Current U.S. public health regulatory restrictions specific to rodent importation pertain only to those of African origin. To understand the impacts of these regulations and the potential public health risks of international rodent trade to the United States, we evaluated live rodent import records during 1999 –2013 by shipment volume and geographic origin, source (e.g., wild -caught versus captive-or commercially bred), intended purpose, and rodent taxonomy. Live rodent imports increased from 2,737 animals during 1999 to 173,761 animals during 2013. Increases in both the number and size of shipments contributed to this trend. The proportion of wild-captured imports declined from 75% during 1999 to <1% during 2013. Nearly all shipments during these years were imported for commercial purposes. Imports from Europe and other countries in North America experienced notable increases in volume. Gerbils and hamsters arriving from Europe and chinchillas, guinea pigs, and hamsters arriving from other countries in North America were predominant taxa underlying this trend . After 2003, African-origin imports became sporadic events under the federal permit process. These patterns suggest development of large -scale captive rodent breeding markets abroad for commercial sale in the United States. While the shift from wild-captured imports alleviates many conservation concerns and risks for novel disease emergence, such consolidated sourcing might elevate exposure risks for zoonotic diseases associated with high-density rodent breeding(e.g. , lymphocytic choriomeningitis or salmonellosis). A responsive border health system must periodically re-evaluate importation regulations in conjunction with key stakeholders to ensure a balance between the economic benefits of rodent trade against the potential public health risks. PMID:26245515

  15. Public Health Implications of Changing Rodent Importation Patterns - United States, 1999-2013.

    PubMed

    Lankau, E W; Sinclair, J R; Schroeder, B A; Galland, G G; Marano, N

    2017-04-01

    The United States imports a large volume of live wild and domestic animal species; these animals pose a demonstrated risk for introduction of zoonotic diseases. Rodents are imported for multiple purposes, including scientific research, zoo exhibits and the pet trade. Current U.S. public health regulatory restrictions specific to rodent importation pertain only to those of African origin. To understand the impacts of these regulations and the potential public health risks of international rodent trade to the United States, we evaluated live rodent import records during 1999-2013 by shipment volume and geographic origin, source (e.g. wild-caught versus captive- or commercially bred), intended purpose and rodent taxonomy. Live rodent imports increased from 2737 animals during 1999 to 173 761 animals during 2013. Increases in both the number and size of shipments contributed to this trend. The proportion of wild-captured imports declined from 75% during 1999 to <1% during 2013. Nearly all shipments during these years were imported for commercial purposes. Imports from Europe and other countries in North America experienced notable increases in volume. Gerbils and hamsters arriving from Europe and chinchillas, guinea pigs and hamsters arriving from other countries in North America were predominant taxa underlying this trend. After 2003, African-origin imports became sporadic events under the federal permit process. These patterns suggest development of large-scale captive rodent breeding markets abroad for commercial sale in the United States. While the shift from wild-captured imports alleviates many conservation concerns and risks for novel disease emergence, such consolidated sourcing might elevate exposure risks for zoonotic diseases associated with high-density rodent breeding (e.g. lymphocytic choriomeningitis or salmonellosis). A responsive border health system must periodically re-evaluate importation regulations in conjunction with key stakeholders to ensure a balance between the economic benefits of rodent trade against the potential public health risks. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  16. Phase-amplitude coupling and infraslow (<1 Hz) frequencies in the rat brain: relationship to resting state fMRI

    PubMed Central

    Thompson, Garth J.; Pan, Wen-Ju; Billings, Jacob C. W.; Grooms, Joshua K.; Shakil, Sadia; Jaeger, Dieter; Keilholz, Shella D.

    2014-01-01

    Resting state functional magnetic resonance imaging (fMRI) can identify network alterations that occur in complex psychiatric diseases and behaviors, but its interpretation is difficult because the neural basis of the infraslow BOLD fluctuations is poorly understood. Previous results link dynamic activity during the resting state to both infraslow frequencies in local field potentials (LFP) (<1 Hz) and band-limited power in higher frequency LFP (>1 Hz). To investigate the relationship between these frequencies, LFPs were recorded from rats under two anesthetics: isoflurane and dexmedetomidine. Signal phases were calculated from low-frequency LFP and compared to signal amplitudes from high-frequency LFP to determine if modulation existed between the two frequency bands (phase-amplitude coupling). Isoflurane showed significant, consistent phase-amplitude coupling at nearly all pairs of frequencies, likely due to the burst-suppression pattern of activity that it induces. However, no consistent phase-amplitude coupling was observed in rats that were anesthetized with dexmedetomidine. fMRI-LFP correlations under isoflurane using high frequency LFP were reduced when the low frequency LFP's influence was accounted for, but not vice-versa, or in any condition under dexmedetomidine. The lack of consistent phase-amplitude coupling under dexmedetomidine and lack of shared variance between high frequency and low frequency LFP as it relates to fMRI suggests that high and low frequency neural electrical signals may contribute differently, possibly even independently, to resting state fMRI. This finding suggests that researchers take care in interpreting the neural basis of resting state fMRI, as multiple dynamic factors in the underlying electrophysiology could be driving any particular observation. PMID:24904325

  17. A case for motor network contributions to schizophrenia symptoms: Evidence from resting-state connectivity.

    PubMed

    Bernard, Jessica A; Goen, James R M; Maldonado, Ted

    2017-09-01

    Though schizophrenia (SCZ) is classically defined based on positive symptoms and the negative symptoms of the disease prove to be debilitating for many patients, motor deficits are often present as well. A growing literature highlights the importance of motor systems and networks in the disease, and it may be the case that dysfunction in motor networks relates to the pathophysiology and etiology of SCZ. To test this and build upon recent work in SCZ and in at-risk populations, we investigated cortical and cerebellar motor functional networks at rest in SCZ and controls using publically available data. We analyzed data from 82 patients and 88 controls. We found key group differences in resting-state connectivity patterns that highlight dysfunction in motor circuits and also implicate the thalamus. Furthermore, we demonstrated that in SCZ, these resting-state networks are related to both positive and negative symptom severity. Though the ventral prefrontal cortex and corticostriatal pathways more broadly have been implicated in negative symptom severity, here we extend these findings to include motor-striatal connections, as increased connectivity between the primary motor cortex and basal ganglia was associated with more severe negative symptoms. Together, these findings implicate motor networks in the symptomatology of psychosis, and we speculate that these networks may be contributing to the etiology of the disease. Overt motor deficits in SCZ may signal underlying network dysfunction that contributes to the overall disease state. Hum Brain Mapp 38:4535-4545, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Enriched Housing Reduces Disease Susceptibility to Co-Infection with Porcine Reproductive and Respiratory Virus (PRRSV) and Actinobacillus pleuropneumoniae (A. pleuropneumoniae) in Young Pigs

    PubMed Central

    van Dixhoorn, Ingrid D. E.; Reimert, Inonge; Middelkoop, Jenny; Bolhuis, J. Elizabeth; Wisselink, Henk J.; Groot Koerkamp, Peter W. G.; Kemp, Bas; Stockhofe-Zurwieden, Norbert

    2016-01-01

    Until today, anti-microbial drugs have been the therapy of choice to combat bacterial diseases. Resistance against antibiotics is of growing concern in man and animals. Stress, caused by demanding environmental conditions, can reduce immune protection in the host, influencing the onset and outcome of infectious diseases. Therefore psychoneuro-immunological intervention may prove to be a successful approach to diminish the impact of diseases and antibiotics use. This study was designed to investigate the effect of social and environmental enrichment on the impact of disease, referred to as “disease susceptibility”, in pigs using a co-infection model of PRRSV and A. pleuropneumoniae. Twenty-eight pigs were raised in four pens under barren conditions and twenty-eight other pigs were raised in four pens under enriched conditions. In the enriched pens a combination of established social and environmental enrichment factors were introduced. Two pens of the barren (BH) and two pens of the enriched housed (EH) pigs were infected with PRRSV followed by A. pleuropneumoniae, the other two pens in each housing treatment served as control groups. We tested if differences in disease susceptibility in terms of pathological and clinical outcome were related to the different housing regimes and if this was reflected in differences in behavioural and immunological states of the animals. Enriched housed pigs showed a faster clearance of viral PRRSV RNA in blood serum (p = 0.014) and histologically 2.8 fold less interstitial pneumonia signs in the lungs (p = 0.014). More barren housed than enriched housed pigs developed lesions in the lungs (OR = 19.2, p = 0.048) and the lesions in the barren housed pigs showed a higher total pathologic tissue damage score (p<0.001) than those in enriched housed pigs. EH pigs showed less stress-related behaviour and differed immunologically and clinically from BH pigs. We conclude that enriched housing management reduces disease susceptibility to co-infection of PRRSV and A. pleuropneumoniae in pigs. Enrichment positively influences behavioural state, immunological response and clinical outcome in pigs. PMID:27606818

  19. Enriched Housing Reduces Disease Susceptibility to Co-Infection with Porcine Reproductive and Respiratory Virus (PRRSV) and Actinobacillus pleuropneumoniae (A. pleuropneumoniae) in Young Pigs.

    PubMed

    van Dixhoorn, Ingrid D E; Reimert, Inonge; Middelkoop, Jenny; Bolhuis, J Elizabeth; Wisselink, Henk J; Groot Koerkamp, Peter W G; Kemp, Bas; Stockhofe-Zurwieden, Norbert

    2016-01-01

    Until today, anti-microbial drugs have been the therapy of choice to combat bacterial diseases. Resistance against antibiotics is of growing concern in man and animals. Stress, caused by demanding environmental conditions, can reduce immune protection in the host, influencing the onset and outcome of infectious diseases. Therefore psychoneuro-immunological intervention may prove to be a successful approach to diminish the impact of diseases and antibiotics use. This study was designed to investigate the effect of social and environmental enrichment on the impact of disease, referred to as "disease susceptibility", in pigs using a co-infection model of PRRSV and A. pleuropneumoniae. Twenty-eight pigs were raised in four pens under barren conditions and twenty-eight other pigs were raised in four pens under enriched conditions. In the enriched pens a combination of established social and environmental enrichment factors were introduced. Two pens of the barren (BH) and two pens of the enriched housed (EH) pigs were infected with PRRSV followed by A. pleuropneumoniae, the other two pens in each housing treatment served as control groups. We tested if differences in disease susceptibility in terms of pathological and clinical outcome were related to the different housing regimes and if this was reflected in differences in behavioural and immunological states of the animals. Enriched housed pigs showed a faster clearance of viral PRRSV RNA in blood serum (p = 0.014) and histologically 2.8 fold less interstitial pneumonia signs in the lungs (p = 0.014). More barren housed than enriched housed pigs developed lesions in the lungs (OR = 19.2, p = 0.048) and the lesions in the barren housed pigs showed a higher total pathologic tissue damage score (p<0.001) than those in enriched housed pigs. EH pigs showed less stress-related behaviour and differed immunologically and clinically from BH pigs. We conclude that enriched housing management reduces disease susceptibility to co-infection of PRRSV and A. pleuropneumoniae in pigs. Enrichment positively influences behavioural state, immunological response and clinical outcome in pigs.

  20. Can Raman spectroscopy identify the origin of Paget disease?

    NASA Astrophysics Data System (ADS)

    Martin, A. A.; Marcelo, Moreno; Bitar, R.; Martinho, H., .; Santos, E. A. P.; Arisawa, E. A. L.

    2008-02-01

    The histogenesis of the breast Paget's disease was investigated by the optical diagnosis technique using Raman spectroscopy. A total of 15 spectra of the associated breast lesion, 21 spectra of the eczematoid skin lesion and 396 spectra of invasive breast cancer not otherwise specified were compared by clustering the spectral data between 800 - 1800 cm -1 at level of similarity of 95%, using a correlation distance measurement by computing the covariance matrix. The Raman spectral-biochemical characterization of invasive breast cancer and breast Paget's disease with eczematoid skin lesion associated with underlying invasive breast lesion tissues enabled one concludes that the parenchymal disease had similar characteristics to the skin's Paget lesion. This could indicate a similar histogenesis for both. Thus, the findings of the present work adds a relevant experimental evidence that agrees with the epidermotropic theory of Paget's disease, that states that the cells originate in the breast ducts and migrate to the nipple's skin.

  1. Dietary fatty acids linking postprandial metabolic response and chronic diseases.

    PubMed

    Ortega, Almudena; Varela, Lourdes M; Bermudez, Beatriz; Lopez, Sergio; Abia, Rocio; Muriana, Francisco J G

    2012-01-01

    Chronic diseases are by far one of the main causes of mortality in the world. One of the current global recommendations to counteract disability and premature death resulting from chronic diseases is to decrease the consumption of energy-dense high-fat diets, particularly those rich in saturated fatty acids (SFA). The most effective replacement for SFA in terms of risk factor outcomes for chronic disease are polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA). The biochemical basis for healthy benefits of such a dietary pattern has been widely evaluated under fasting conditions. However, the increasing amount of data available from multiple studies suggest that the postprandial state, i.e., "the period that comprises and follows a meal", plays an important, yet underappreciated, role in the genesis of numerous pathological conditions. In this review, the potential of MUFA, PUFA, and SFA to postprandially affect selected metabolic abnormalities related to chronic diseases is discussed.

  2. Neuropsychiatric symptoms and celiac disease.

    PubMed

    Urban-Kowalczyk, Małgorzata; OEmigielski, Janusz; Gmitrowicz, Agnieszka

    2014-01-01

    Neuropsychiatric symptoms may represent an atypical manifestation of celiac disease that occur before a gastroenterological diagnosis is made. Some studies suggest that a gluten-free diet is effective in treating the depression, anxiety, and neurological complications associated with celiac disease. The article describes the case of a patient suffering from chronic, treatment-resistant symptoms of depression and anxiety. The diagnosis of celiac disease and introduction of an elimination diet caused a significant improvement in mental state and everyday functioning in the presenting patient. The presence of persistent anxiety and depressive symptoms, with a poor reaction to pharmacological treatment, indicates a need to identify somatic reasons for the underlying condition. It is important to remember that celiac disease can occur at any age, not only in childhood. The presence of this somatic cause of persistent depressive and anxiety symptoms should be considered in the diagnostic process in adults.

  3. [Neurosis as a mental disease--controversies surrounding insurance certification].

    PubMed

    Jabłoński, Christian; Kobek, Mariusz; Kowalczyk-Jabłońska, Dorota

    2011-01-01

    In the years 2008-2009, experts from the Department of Forensic Medicine in Katowice issued a dozen of expert opinions on the nature of the neurosis, addressing the question whether neurosis is a mental disease as understood under the general insurance conditions or whether neurosis is a mental disease as such. All the submitted cases involved policemen who had been diagnosed as neurotic and were refused insurance payments since the insurance company claimed payments could not have been effected due to the diagnosis of mental disease, meaning neurosis in the discussed cases. The plaintiffs invoked the fact that medical terminology describes such states as "mental disorders". In the article, the authors present the adopted model of opinionating, make an attempt at explaining the controversy and discuss the subtleties of medical terminology and the core differences between the terms "mental disorder" and "mental disease" as employed in medico-legal opinionating in such cases.

  4. Epidemiological Trends of Dengue Disease in Mexico (2000–2011): A Systematic Literature Search and Analysis

    PubMed Central

    Dantés, Héctor Gómez; Farfán-Ale, José Arturo; Sarti, Elsa

    2014-01-01

    This systematic literature review describes the epidemiology of dengue disease in Mexico (2000–2011). The annual number of uncomplicated dengue cases reported increased from 1,714 in 2000 to 15,424 in 2011 (incidence rates of 1.72 and 14.12 per 100,000 population, respectively). Peaks were observed in 2002, 2007, and 2009. Coastal states were most affected by dengue disease. The age distribution pattern showed an increasing number of cases during childhood, a peak at 10–20 years, and a gradual decline during adulthood. All four dengue virus serotypes were detected. Although national surveillance is in place, there are knowledge gaps relating to asymptomatic cases, primary/secondary infections, and seroprevalence rates of infection in all age strata. Under-reporting of the clinical spectrum of the disease is also problematic. Dengue disease remains a serious public health problem in Mexico. PMID:25375162

  5. Hypertriglyceridemia Influences the Degree of Postprandial Lipemic Response in Patients with Metabolic Syndrome and Coronary Artery Disease: From the Cordioprev Study

    PubMed Central

    Alcala-Diaz, Juan F.; Delgado-Lista, Javier; Perez-Martinez, Pablo; Garcia-Rios, Antonio; Marin, Carmen; Quintana-Navarro, Gracia M.; Gomez-Luna, Purificacion; Camargo, Antonio; Almaden, Yolanda; Caballero, Javier; Tinahones, Francisco J.; Ordovas, Jose M.

    2014-01-01

    Objective To determine whether metabolic syndrome traits influence the postprandial lipemia response of coronary patients, and whether this influence depends on the number of MetS criteria. Materials and Methods 1002 coronary artery disease patients from the CORDIOPREV study were submitted to an oral fat load test meal with 0.7 g fat/kg body weight (12% saturated fatty acids, 10% polyunsaturated fatty acids, 43% monounsaturated fatty acids), 10% protein and 25% carbohydrates. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 hours during the postprandial state. Total and incremental area under the curves of the different postprandial parameters were calculated following the trapezoid rule to assess the magnitude of change during the postprandial state Results Postprandial lipemia response was directly related to the presence of metabolic syndrome. We found a positive association between the number of metabolic syndrome criteria and the response of postprandial plasma triglycerides (p<0.001), area under the curve of triglycerides (p<0.001) and incremental area under the curve of triglycerides (p<0.001). However, the influence of them on postprandial triglycerides remained statistically significant only in those patients without basal hypertriglyceridemia. Interestingly, in stepwise multiple linear regression analysis with the AUC of triglycerides as the dependent variable, only fasting triglycerides, fasting glucose and waist circumference appeared as significant independent (P<0.05) contributors. The multiple lineal regression (R) was 0.77, and fasting triglycerides showed the greatest effect on AUC of triglycerides with a standardized coefficient of 0.75. Conclusions Fasting triglycerides are the major contributors to the postprandial triglycerides levels. MetS influences the postprandial response of lipids in patients with coronary heart disease, particularly in non-hypertriglyceridemic patients. PMID:24802225

  6. Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson's disease.

    PubMed

    Le Heron, Campbell; Plant, Olivia; Manohar, Sanjay; Ang, Yuen-Siang; Jackson, Matthew; Lennox, Graham; Hu, Michele T; Husain, Masud

    2018-05-01

    Effort-based decision-making is a cognitive process crucial to normal motivated behaviour. Apathy is a common and disabling complication of Parkinson's disease, but its aetiology remains unclear. Intriguingly, the neural substrates associated with apathy also subserve effort-based decision-making in animal models and humans. Furthermore, the dopaminergic system plays a core role in motivating effortful behaviour for reward, and its dysfunction has been proposed to play a crucial role in the aetiology of apathy in Parkinson's disease. We hypothesized that disrupted effort-based decision-making underlies the syndrome of apathy in Parkinson's disease, and that this disruption may be modulated by the dopaminergic system. An effort-based decision-making task was administered to 39 patients with Parkinson's disease, with and without clinical apathy, ON and OFF their normal dopaminergic medications across two separate sessions, as well as 32 healthy age- and gender-matched controls. On a trial-by-trial basis, participants decided whether to accept or reject offers of monetary reward in return for exerting different levels of physical effort via handheld, individually calibrated dynamometers. Effort and reward were manipulated independently, such that offers spanned the full range of effort/reward combinations. Apathy was assessed using the Lille apathy rating scale. Motor effects of the dopamine manipulation were assessed using the Unified Parkinson's Disease Rating Scale part three motor score. The primary outcome variable was choice (accept/decline offer) analysed using a hierarchical generalized linear mixed effects model, and the vigour of squeeze (Newtons exerted above required force). Both apathy and dopamine depletion were associated with reduced acceptance of offers. However, these effects were driven by dissociable patterns of responding. While apathy was characterized by increased rejection of predominantly low reward offers, dopamine increased responding to high effort, high reward offers, irrespective of underlying motivational state. Dopamine also exerted a main effect on motor vigour, increasing force production independently of reward offered, while apathy did not affect this measure. The findings demonstrate that disrupted effort-based decision-making underlies Parkinson's disease apathy, but in a manner distinct to that caused by dopamine depletion. Apathy is associated with reduced incentivization by the rewarding outcomes of actions. In contrast, dopamine has a general effect in motivating behaviour for high effort, high reward options without altering the response pattern that characterizes the apathetic state. Thus, the motivational deficit observed in Parkinson's disease appears not to be simply secondary to dopaminergic depletion of mesocorticolimbic pathways, suggesting non-dopaminergic therapeutic strategies for apathy may be important future targets.

  7. Integrin antagonists as potential therapeutic options for the treatment of Crohn’s disease

    PubMed Central

    McLean, Leon P.; Cross, Raymond K.

    2016-01-01

    Introduction Anti-integrin therapy for the treatment of patients with Crohn’s disease is rapidly evolving. Two agents, natalizumab and vedolizumab, are approved by the United States Food and Drug Administration for the treatment of Crohn’s disease, with vedolizumab the primary anti-integrin used due to a more favorable safety profile. Several other anti-integrins are in various stages of development. Areas Covered This review discusses the current state of anti-integrin therapy as well as suggestions for positioning of these agents in clinical practice. Emerging anti-integrin therapies, their underlying mechanisms of action, and available safety and clinical data are also reviewed. Expert Opinion Anti-integrins are effective for the treatment of Crohn’s disease, even in patients refractory to other therapies. Their use should be considered in patients with Crohn’s disease who do not respond to, develop non-response to, or have contraindications to anti-TNF therapy. Anti-integrin therapies can be offered as a first biologic therapy, in particular for older patients, patients with concurrent multiple sclerosis (natalizumab only), and in patients with contraindications to anti-TNF therapy. In patients with more severe symptoms, providers should consider co-induction with corticosteroids if possible to hasten remission. PMID:26822204

  8. The main sceneries of Chagas disease transmission. The vectors, blood and oral transmissions - A comprehensive review

    PubMed Central

    Coura, José Rodrigues

    2015-01-01

    This review deals with transmission of Trypanosoma cruzi by the most important domestic vectors, blood transfusion and oral intake. Among the vectors, Triatoma infestans, Panstrongylus megistus, Rhodnius prolixus, Triatoma dimidiata, Triatoma brasiliensis, Triatoma pseudomaculata, Triatoma sordida, Triatoma maculata, Panstrongylus geniculatus, Rhodnius ecuadoriensis and Rhodnius pallescens can be highlighted. Transmission of Chagas infection, which has been brought under control in some countries in South and Central America, remains a great challenge, particularly considering that many endemic countries do not have control over blood donors. Even more concerning is the case of non-endemic countries that receive thousands of migrants from endemic areas that carry Chagas disease, such as the United States of America, in North America, Spain, in Europe, Japan, in Asia, and Australia, in Oceania. In the Brazilian Amazon Region, since Shaw et al. (1969) described the first acute cases of the disease caused by oral transmission, hundreds of acute cases of the disease due to oral transmission have been described in that region, which is today considered to be endemic for oral transmission. Several other outbreaks of acute Chagas disease by oral transmission have been described in different states of Brazil and in other South American countries. PMID:25466622

  9. First report of root rot of cowpea caused by Fusarium equiseti in Georgia in the United States

    USDA-ARS?s Scientific Manuscript database

    Root rot was observed on cowpea in Tift County, Georgia, in May of 2015. The disease occurred on approximately 10% of cowpea plants in 2 fields (2 ha). Symptoms appeared as sunken reddish brown lesions on roots and stems under the soil line, secondary roots became dark brown and rotted, and infected...

  10. Revisiting Tax Benefits for Parents of Children with Special Needs, Part 2

    ERIC Educational Resources Information Center

    Brinker, Thomas M., Jr.; Sherman, W. Richard; Ivers, James F., III

    2010-01-01

    The Center for Disease Control (CDC) estimates that up to 500,000 individuals under the age of 21 have autism, Asperger's syndrome, and other neurological disorders. This translates to an average of 1 in 110 children in the U.S. having an Autism Spectrum Disorder. Autism is now the sixth most commonly classified disability in the United States.…

  11. 76 FR 31499 - Lists of Regions Classified With Respect to Certain Animal Diseases and States Approved To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-01

    ... specified regions. (a) The meat of ruminants or swine, and other animal products, and ship stores, airplane... all parts of the carcass of any ruminant or swine, other than meat and articles regulated under part.... (a) The pork or pork products and ship's stores, airplane meals, and baggage containing pork or pork...

  12. Reflections on Math Reforms in the U.S.: "A Cross-National Perspective"

    ERIC Educational Resources Information Center

    Newton, Xiaoxia

    2007-01-01

    In traditional Chinese medicine, a key maxim is "Zhi Bing Yao Zhi Gen," which literally means, "To cure a disease one must cure the underlying cause." The author was reminded of this principle when she reflects on K-12 math education reform when the US. President Bush's 2006 State of the Union Address prompted yet another wave…

  13. Translation, cross-cultural adaptation and validation of an HIV/AIDS knowledge and attitudinal instrument.

    PubMed

    Zometa, Carlos S; Dedrick, Robert; Knox, Michael D; Westhoff, Wayne; Siri, Rodrigo Simán; Debaldo, Ann

    2007-06-01

    An instrument developed in the United States by the Centers for Disease Control and Prevention to assess HIV/AIDS knowledge and four attitudinal dimensions (Peer Pressure, Abstinence, Drug Use, and Threat of HIV Infection) and an instrument developed by Basen-Engquist et al. (1999) to measure abstinence and condom use were translated, cross-culturally adapted, and validated for use with Spanish-speaking high school students in El Salvador. A back-translation of the English version was cross-culturally adapted using two different review panels and pilot-tested with Salvadorian students. An expert panel established content validity, and confirmatory factor analysis provided support for construct validity. Results indicated that the methodology was successful in cross-culturally adapting the instrument developed by the Centers for Disease Control and Prevention and the instrument developed by Basen-Engquist et al. The psychometric properties of the knowledge section were acceptable and there was partial support for the four-factor attitudinal model underlying the CDC instrument and the two-factor model underlying the Basen-Engquist et al. instrument. Additional studies with Spanish-speaking populations (either in the United States or Latin America) are needed to evaluate the generalizability of the present results.

  14. Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology

    PubMed Central

    Joseph, Jacob; Loscalzo, Joseph

    2013-01-01

    Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or “methoxistasis”, exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure. PMID:23955381

  15. Acquired Amino Acid Deficiencies: A Focus on Arginine and Glutamine.

    PubMed

    Morris, Claudia R; Hamilton-Reeves, Jill; Martindale, Robert G; Sarav, Menaka; Ochoa Gautier, Juan B

    2017-04-01

    Nonessential amino acids are synthesized de novo and therefore not diet dependent. In contrast, essential amino acids must be obtained through nutrition since they cannot be synthesized internally. Several nonessential amino acids may become essential under conditions of stress and catabolic states when the capacity of endogenous amino acid synthesis is exceeded. Arginine and glutamine are 2 such conditionally essential amino acids and are the focus of this review. Low arginine bioavailability plays a pivotal role in the pathogenesis of a growing number of varied diseases, including sickle cell disease, thalassemia, malaria, acute asthma, cystic fibrosis, pulmonary hypertension, cardiovascular disease, certain cancers, and trauma, among others. Catabolism of arginine by arginase enzymes is the most common cause of an acquired arginine deficiency syndrome, frequently contributing to endothelial dysfunction and/or T-cell dysfunction, depending on the clinical scenario and disease state. Glutamine, an arginine precursor, is one of the most abundant amino acids in the body and, like arginine, becomes deficient in several conditions of stress, including critical illness, trauma, infection, cancer, and gastrointestinal disorders. At-risk populations are discussed together with therapeutic options that target these specific acquired amino acid deficiencies.

  16. Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

    PubMed Central

    Chotirmall, Sanjay H.; Al-Alawi, Mazen; Logan, P. Mark; Greene, Catherine M.; McElvaney, Noel G.

    2013-01-01

    Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit. PMID:23971044

  17. Role of information technology (IT) in public health, India (problems & prospects): Role of information communication technology (ICT) in disease surveillance under Integrated Disease Surveillance Project (IDSP).

    PubMed

    Sharma, Rajeev; Luthra, Pallavi; Karad, Amit; Dhariwal, A C; Ichhpujani, R L; Lal, Shiv

    2010-06-01

    Information Communication Technology (ICT) has proven to be a strong public health tool. Keeping the future need of country and building National Disease Surveillance System, Integrated Disease Surveillance Project (IDSP) was launched by Hon'ble Union Minister of Health & Family Welfare in November 2004. It is a decentralized, State based surveillance program in the country. It is intended to detect early warning signals of impending outbreaks and help initiate an effective response in a timely manner. One of the major components of the project is the - use of Information Technology for collection, collation, compilation, analysis and dissemination of data besides distance education and video conferencing. A network of 800 sites across India has been established through Satellite, Broadband and High end Video conferencing equipments. The network is managed by a team of data managers and data entry operators at all state surveillance units and district surveillance units respectively. The network was proven to be extremely useful to respond to the current influenza A H1N1 pandemic. It is proposed to extend the network to cover private sector and provide convergence with other National Health Programs.

  18. Sickle cell disease: renal manifestations and mechanisms

    PubMed Central

    Nath, Karl A.; Hebbel, Robert P.

    2015-01-01

    Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

  19. Genome Editing in Induced Pluripotent Stem Cells using CRISPR/Cas9.

    PubMed

    Ben Jehuda, Ronen; Shemer, Yuval; Binah, Ofer

    2018-06-01

    The development of the reprogramming technology led to generation of induced Pluripotent Stem Cells (iPSC) from a variety of somatic cells. Ever since, fast growing knowledge of different efficient protocols enabled the differentiation of these iPSCs into different cells types utilized for disease modeling. Indeed, iPSC-derived cells have been increasingly used for investigating molecular and cellular pathophysiological mechanisms underlying inherited diseases. However, a major barrier in the field of iPSC-based disease modeling relies on discriminating between the effects of the causative mutation and the genetic background of these cells. In the past decade, researchers have made great improvement in genome editing techniques, with one of the latest being CRISPR/Cas9. Using a single non-sequence specific protein combined with a small guiding RNA molecule, this state-of-the-art approach enables modifications of genes with high efficiency and accuracy. By so doing, this technique enables the generation of isogenic controls or isogenic mutated cell lines in order to focus on the pathologies caused by a specific mutation. In this article, we review the latest studies combining iPSC and CRISPR/Cas9 technologies for the investigation of the molecular and cellular mechanisms underlying inherited diseases including immunological, metabolic, hematological, neurodegenerative and cardiac diseases.

  20. Factors associated with chronic diseases among the elderly receiving treatment under the Family Health Strategy.

    PubMed

    Pimenta, Fernanda Batista; Pinho, Lucinéia; Silveira, Marise Fagundes; Botelho, Ana Cristina de Carvalho

    2015-08-01

    The profile of a sample population of elderly receiving treatment under the Family Health Strategy in the municipality of Teófilo Otoni, State of Minas Gerais, Brazil, is described, and the factors associated with diseases prevalence examined. Using simple random sampling, 385 elderly were interviewed using Form A and Elderly Form from the Primary Health Care Information System. The majority of the sample (83.1%) self-reported at least one disease, 69.9% had hypertension, and 17.7% had diabetes. Poisson regression analysis showed that the main factors associated with hypertension and other diseases were being non-white, having a low level of education, medication use, dental prosthesis use, and lack of a private health plan. The prevalence of diabetes was greater among women and individuals who depended on other people to live. It can be concluded that this sample population of elderly has a generally low socioeconomic status and are more susceptible to developing diseases, particularly hypertension. Diabetes should be controlled although had relatively low prevalence. It is suggested investments in structuring the health system network to provide adequate care for the elderly and in training health professionals to play an effective role in improving the quality of life of the elderly in Brazil.

  1. Impact of gastrointestinal disease states on oral drug absorption - implications for formulation design - a PEARRL review.

    PubMed

    Effinger, Angela; O'Driscoll, Caitriona M; McAllister, Mark; Fotaki, Nikoletta

    2018-05-16

    Drug product performance in patients with gastrointestinal (GI) diseases can be altered compared to healthy subjects due to pathophysiological changes. In this review, relevant differences in patients with inflammatory bowel diseases, coeliac disease, irritable bowel syndrome and short bowel syndrome are discussed and possible in vitro and in silico tools to predict drug product performance in this patient population are assessed. Drug product performance was altered in patients with GI diseases compared to healthy subjects, as assessed in a limited number of studies for some drugs. Underlying causes can be observed pathophysiological alterations such as the differences in GI transit time, the composition of the GI fluids and GI permeability. Additionally, alterations in the abundance of metabolising enzymes and transporter systems were observed. The effect of the GI diseases on each parameter is not always evident as it may depend on the location and the state of the disease. The impact of the pathophysiological change on drug bioavailability depends on the physicochemical characteristics of the drug, the pharmaceutical formulation and drug metabolism. In vitro and in silico methods to predict drug product performance in patients with GI diseases are currently limited but could be a useful tool to improve drug therapy. Development of suitable in vitro dissolution and in silico models for patients with GI diseases can improve their drug therapy. The likeliness of the models to provide accurate predictions depends on the knowledge of pathophysiological alterations, and thus, further assessment of physiological differences is essential. © 2018 Royal Pharmaceutical Society.

  2. The risk of bovine spongiform encephalopathy ('mad cow disease') to human health.

    PubMed

    Brown, P

    1997-09-24

    Some human cases of the transmissible neurodegenerative disorder Creutzfeldt-Jakob disease recently seen in Great Britain are thought to have resulted from eating beef infected with the agent of bovine spongiform encephalopathy. Reasons for and against this presumption are explained, and the question of a similar situation occurring in countries other than Britain-in particular, the United States-is discussed in terms of the existence of scrapie (in sheep) or unrecognized bovine spongiform encephalopathy (in cattle), the practice of recycling nonedible sheep and cattle tissue for animal nutrition, and precautionary measures already taken or under consideration by government agencies

  3. The role of the Department of Homeland Security, Science and Technology Directorate in the development of vaccines and diagnostics for Transboundary Animal Diseases.

    PubMed

    Colby, M; Coats, M; Brake, D; Fine, J

    2013-01-01

    The development of countermeasures to support an effective response to Transboundary Animal Diseases (TAD) poses a challenge on a global scale and necessitates the coordinated involvement of scientists from government, industry and academia, as well as regulatory entities. The Agricultural Defense Branch under the Chemical and Biological Defense Division (CBD) of the Department of Homeland Security (DHS), Science and Technology Directorate (S&T) supports this important mission within the United States. This article provides an overview of the Agricultural Defense Branch's vaccine and diagnostic TAD project.

  4. Deaths: Leading Causes for 2015.

    PubMed

    Heron, Melonie

    2017-11-01

    Objectives-This report presents final 2015 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2015," the National Center for Health Statistics' annual report of final mortality statistics. Methods-Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2015. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. Results-In 2015, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer's disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2015 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

  5. Deaths: Leading Causes for 2013.

    PubMed

    Heron, Melonie

    2016-02-16

    This report presents final 2013 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements "Deaths: Final Data for 2013," the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2013. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2013, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Accidents (unintentional injuries); Cerebrovascular diseases; Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2013 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Newborn affected by maternal complications of pregnancy; Sudden infant death syndrome; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

  6. Deaths: leading causes for 2010.

    PubMed

    Heron, Melonie

    2013-12-20

    This report presents final 2010 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the Division of Vital Statistics' annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2010. Causes of death classified by the International Classification of Diseases, Tenth Revision (ICD-10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2010, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer's disease; Diabetes mellitus; Nephritis, nephrotic syndrome and nephrosis; Influenza and pneumonia; and Intentional self-harm (suicide). These 10 causes accounted for 75% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2010 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Necrotizing enterocolitis of newborn. Important variations in the leading causes of infant death are noted for the neonatal and post-neonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

  7. Deaths: Leading Causes for 2011.

    PubMed

    Heron, Melonie

    2015-07-27

    This report presents final 2011 data on the 10 leading causes of death in the United States by age, sex, race, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements ‘‘Deaths: Final Data for 2011,’’ the National Center for Health Statistics’ annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 states and the District of Columbia in 2011. Causes of death classified by the International Classification of Diseases, 10th Revision (ICD–10) are ranked according to the number of deaths assigned to rankable causes. Cause-of-death statistics are based on the underlying cause of death. In 2011, the 10 leading causes of death were, in rank order: Diseases of heart; Malignant neoplasms; Chronic lower respiratory diseases; Cerebrovascular diseases; Accidents (unintentional injuries); Alzheimer’s disease; Diabetes mellitus; Influenza and pneumonia; Nephritis, nephrotic syndrome and nephrosis; and Intentional self-harm (suicide). They accounted for 74% of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2011 were, in rank order: Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Accidents (unintentional injuries); Newborn affected by complications of placenta, cord and membranes; Bacterial sepsis of newborn; Respiratory distress of newborn; Diseases of the circulatory system; and Neonatal hemorrhage. Important variations in the leading causes of infant death are noted for the neonatal and postneonatal periods. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

  8. Human skin pigmentation, migration and disease susceptibility

    PubMed Central

    Jablonski, Nina G.; Chaplin, George

    2012-01-01

    Human skin pigmentation evolved as a compromise between the conflicting physiological demands of protection against the deleterious effects of ultraviolet radiation (UVR) and photosynthesis of UVB-dependent vitamin D3. Living under high UVR near the equator, ancestral Homo sapiens had skin rich in protective eumelanin. Dispersals outside of the tropics were associated with positive selection for depigmentation to maximize cutaneous biosynthesis of pre-vitamin D3 under low and highly seasonal UVB conditions. In recent centuries, migrations and high-speed transportation have brought many people into UVR regimes different from those experienced by their ancestors and, accordingly, exposed them to new disease risks. These have been increased by urbanization and changes in diet and lifestyle. Three examples—nutritional rickets, multiple sclerosis (MS) and cutaneous malignant melanoma (CMM)—are chosen to illustrate the serious health effects of mismatches between skin pigmentation and UVR. The aetiology of MS in particular provides insight into complex and contingent interactions of genetic and environmental factors necessary to trigger lethal disease states. Low UVB levels and vitamin D deficiencies produced by changes in location and lifestyle pose some of the most serious disease risks of the twenty-first century. PMID:22312045

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

    NASA Astrophysics Data System (ADS)

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

    2016-11-01

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

  10. Subfractions of high-density lipoprotein (HDL) and dysfunctional HDL in chronic kidney disease patients.

    PubMed

    Rysz-Górzyńska, Magdalena; Banach, Maciej

    2016-08-01

    A number of studies have shown that chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease (CVD). Chronic kidney disease is characterized by significant disturbances in lipoprotein metabolism, including differences in quantitative and qualitative content of high-density lipoprotein (HDL) particles. Recent studies have revealed that serum HDL cholesterol levels do not predict CVD in CKD patients; thus CKD-induced modifications in high-density lipoprotein (HDL) may be responsible for the increase in CV risk in CKD patients. Various methods are available to separate several subclasses of HDL and confirm their atheroprotective properties. However, under pathological conditions associated with inflammation and oxidation, HDL can progressively lose normal biological activities and be converted into dysfunctional HDL. In this review, we highlight the current state of knowledge on subfractions of HDL and HDL dysfunction in CKD.

  11. Autoregulation of Parkin activity through its ubiquitin-like domain

    PubMed Central

    Chaugule, Viduth K; Burchell, Lynn; Barber, Kathryn R; Sidhu, Ateesh; Leslie, Simon J; Shaw, Gary S; Walden, Helen

    2011-01-01

    Parkin is an E3-ubiquitin ligase belonging to the RBR (RING–InBetweenRING–RING family), and is involved in the neurodegenerative disorder Parkinson's disease. Autosomal recessive juvenile Parkinsonism, which is one of the most common familial forms of the disease, is directly linked to mutations in the parkin gene. However, the molecular mechanisms of Parkin dysfunction in the disease state remain to be established. We now demonstrate that the ubiquitin-like domain of Parkin functions to inhibit its autoubiquitination. Moreover pathogenic Parkin mutations disrupt this autoinhibition, resulting in a constitutively active molecule. In addition, we show that the mechanism of autoregulation involves ubiquitin binding by a C-terminal region of Parkin. Our observations provide important molecular insights into the underlying basis of Parkinson's disease, and in the regulation of RBR E3-ligase activity. PMID:21694720

  12. Ghrelin and cachexia in chronic kidney disease.

    PubMed

    Suzuki, Hajime; Asakawa, Akihiro; Amitani, Haruka; Nakamura, Norifumi; Inui, Akio

    2013-04-01

    Ghrelin is a growth hormone (GH) secretagogue and a potent orexigenic factor that stimulates feeding by interacting with hypothalamic feeding-regulatory nuclei. Its multifaceted effects are potentially beneficial as a treatment in human disease states. In both adult and pediatric chronic kidney disease (CKD) patients, decreased appetite plays a major role in wasting, which in turn is linked to morbidity and mortality; wasting has also been linked to high levels of leptin and proinflammatory cytokines. The beneficial effects of ghrelin treatment in CKD are potentially mediated by multiple concurrent actions, including the stimulation of appetite-regulating centers, anti-inflammatory effects, and direct kidney effects. Further evaluation of this appetite-regulating hormone in CKD is needed to confirm previous findings and to determine the underlying mechanisms.

  13. Astroglial and microglial contributions to iron metabolism disturbance in Parkinson's disease.

    PubMed

    Song, Ning; Wang, Jun; Jiang, Hong; Xie, Junxia

    2018-03-01

    Understandings of the disturbed iron metabolism in Parkinson's disease (PD) are largely from the perspectives of neurons. Neurodegenerative processes in PD trigger universal and conserved astroglial dysfunction and microglial activation. In this review, we start with astroglia and microglia in PD with an emphasis on their roles in spreading α-synuclein pathology, and then focus on their contributions in iron metabolism under normal conditions and the diseased state of PD. Elevated iron in the brain regions affects glial features, meanwhile, glial effects on neuronal iron metabolism are largely dependent on their releasing factors. These advances might be valuable for better understanding and modulating iron metabolism disturbance in PD. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Crossed wires: 3D genome misfolding in human disease.

    PubMed

    Norton, Heidi K; Phillips-Cremins, Jennifer E

    2017-11-06

    Mammalian genomes are folded into unique topological structures that undergo precise spatiotemporal restructuring during healthy development. Here, we highlight recent advances in our understanding of how the genome folds inside the 3D nucleus and how these folding patterns are miswired during the onset and progression of mammalian disease states. We discuss potential mechanisms underlying the link among genome misfolding, genome dysregulation, and aberrant cellular phenotypes. We also discuss cases in which the endogenous 3D genome configurations in healthy cells might be particularly susceptible to mutation or translocation. Together, these data support an emerging model in which genome folding and misfolding is critically linked to the onset and progression of a broad range of human diseases. © 2017 Norton and Phillips-Cremins.

  15. Synaptic plasticity in sleep: learning, homeostasis, and disease

    PubMed Central

    Wang, Gordon; Grone, Brian; Colas, Damien; Appelbaum, Lior; Mourrain, Philippe

    2012-01-01

    Sleep is a fundamental and evolutionarily conserved aspect of animal life. Recent studies have shed light on the role of sleep in synaptic plasticity. Demonstrations of memory replay and synapse homeostasis suggest that one essential role of sleep is in the consolidation and optimization of synaptic circuits to retain salient memory traces despite the noise of daily experience. Here, we review this recent evidence, and suggest that sleep creates a heightened state of plasticity, which may be essential for this optimization. Furthermore, we discuss how sleep deficits seen in diseases such as Alzheimer’s disease and autism spectrum disorders might not just reflect underlying circuit malfunction, but could also play a direct role in the progression of those disorders. PMID:21840068

  16. Noncoding RNAs and chronic inflammation: Micro-managing the fire within.

    PubMed

    Alexander, Margaret; O'Connell, Ryan M

    2015-09-01

    Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age-associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets. © 2015 The Authors. BioEssays published by WILEY Periodicals, Inc.

  17. Affected sib pair tests in inbred populations.

    PubMed

    Liu, W; Weir, B S

    2004-11-01

    The affected-sib-pair (ASP) method for detecting linkage between a disease locus and marker loci was first established 50 years ago, and since then numerous modifications have been made. We modify two identity-by-state (IBS) test statistics of Lange (Lange, 1986a, 1986b) to allow for inbreeding in the population. We evaluate the power and false positive rates of the modified tests under three disease models, using simulated data. Before estimating false positive rates, we demonstrate that IBS tests are tests of both linkage and linkage disequilibrium between marker and disease loci. Therefore, the null hypothesis of IBS tests should be no linkage and no LD. When the population inbreeding coefficient is large, the false positive rates of Lange's tests become much larger than the nominal value, while those of our modified tests remain close to the nominal value. To estimate power with a controlled false positive rate, we choose the cutoff values based on simulated datasets under the null hypothesis, so that both Lange's tests and the modified tests generate same false positive rate. The powers of Lange's z-test and our modified z-test are very close and do not change much with increasing inbreeding. The power of the modified chi-square test also stays stable when the inbreeding coefficient increases. However, the power of Lange's chi-square test increases with increasing inbreeding, and is larger than that of our modified chi-square test for large inbreeding coefficients. The power is high under a recessive disease model for both Lange's tests and the modified tests, though the power is low for additive and dominant disease models. Allowing for inbreeding is therefore appropriate, at least for diseases known to be recessive.

  18. The role of industry in the development of a product for control of mycoplasmal plant diseases.

    PubMed

    Carroll, V J

    1982-01-01

    A number of mycoplasmal or mycoplasma-like diseases of plants have been treated with an oxytetracycline-based product. Remission of symptoms has generally resulted, and in some instances the local use of this product under temporary governmental registrations has been approved. The use of oxytetracycline for control of many such diseases is not commercially feasible because the potential market is relatively small and the costs of development are relatively high. However, oxytetracycline products may be useful when a disease problem becomes sufficiently serious to arouse academic attention and agricultural or public concern. The commercial use of oxytetracycline hydrochloride for remission and prevention of lethal yellowing of coconut palm was begun in 1974. Use of this product for control of pear decline disease followed shortly thereafter. To date, joint participation and cooperation of the drug and agricultural industries have also resulted in the control of two important mycoplasma-like diseases of peach trees in the United States.

  19. Essential veterinary education in emerging infections, modes of introduction of exotic animals, zoonotic diseases, bioterrorism, implications for human and animal health and disease manifestation.

    PubMed

    Chomel, B B; Marano, N

    2009-08-01

    A fundamental role of the veterinary profession is the protection of human health through wholesome food and control of diseases of animal origin, especially zoonoses. Therefore, training of veterinary students worldwide needs to face the new challenges posed by emerging infections, both from wildlife and domestic animals, as well as risks from bio/agroterrorism. New courses emphasising recognition, response, recovery and prevention must be developed to respond to natural or intentionally induced emerging diseases and zoonoses. Training programmes in applied epidemiology, zoonoses and foreign animal diseases are crucial for the development of a strong workforce to deal with microbial threats. Students should learn the reporting pathways for reportable diseases in their countries or states. Knowledge of the principles of ecology and ecosystems should be acquired during pre-veterinary studies. Elective classes on wildlife diseases, emphasising wildlife zoonotic diseases, should be offered during the veterinary curriculum, as well as a course on risk communication, since veterinarians are frequently in the position of having to convey complex information under adverse circumstances.

  20. Network Approach to Disease Diagnosis

    NASA Astrophysics Data System (ADS)

    Sharma, Amitabh; Bashan, Amir; Barabasi, Alber-Laszlo

    2014-03-01

    Human diseases could be viewed as perturbations of the underlying biological system. A thorough understanding of the topological and dynamical properties of the biological system is crucial to explain the mechanisms of many complex diseases. Recently network-based approaches have provided a framework for integrating multi-dimensional biological data that results in a better understanding of the pathophysiological state of complex diseases. Here we provide a network-based framework to improve the diagnosis of complex diseases. This framework is based on the integration of transcriptomics and the interactome. We analyze the overlap between the differentially expressed (DE) genes and disease genes (DGs) based on their locations in the molecular interaction network (''interactome''). Disease genes and their protein products tend to be much more highly connected than random, hence defining a disease sub-graph (called disease module) in the interactome. DE genes, even though different from the known set of DGs, may be significantly associated with the disease when considering their closeness to the disease module in the interactome. This new network approach holds the promise to improve the diagnosis of patients who cannot be diagnosed using conventional tools. Support was provided by HL066289 and HL105339 grants from the U.S. National Institutes of Health.

  1. Big Data and Heath Impacts of Drinking Water Quality Violation

    NASA Astrophysics Data System (ADS)

    Allaire, M.; Zheng, S.; Lall, U.

    2017-12-01

    Health impacts of drinking water quality violations are only understood at a coarse level in the United States. This limits identification of threats to water security in communities across the country. Substantial under-reporting is suspected due to requirements at U.S. public health institutes that water borne illnesses be confirmed by health providers. In the era of `big data', emerging information sources could offer insight into waterborne disease trends. In this study, we explore the use of fine-resolution sales data for over-the-counter medicine to estimate the health impacts of drinking water quality violations. We also demonstrate how unreported water quality issues can be detected by observing market behavior. We match a panel of supermarket sales data for the U.S. at the weekly level with geocoded violations data from 2006-2015. We estimate the change in anti-diarrheal medicine sale due to drinking water violations using a fixed effects model. We find that water quality violations have considerable effects on medicine sales. Sales nearly double due to Tier 1 violations, which pose an immediate health risk, and sales increase 15.1 percent due to violations related to microorganisms. Furthermore, our estimate of diarrheal illness cases associated with water quality violations indicates that the Centers for Disease Control and Prevention (CDC) reporting system may only capture about one percent of diarrheal cases due to impaired water. Incorporating medicine sales data could offer national public health institutes a game-changing way to improve monitoring of disease outbreaks. Since many disease cases are not formally diagnosed by health providers, consumption information could provide additional information to remedy under-reporting issues and improve water security in communities across the United States.

  2. Quantitative imaging of brain energy metabolisms and neuroenergetics using in vivo X-nuclear 2H, 17O and 31P MRS at ultra-high field.

    PubMed

    Zhu, Xiao-Hong; Lu, Ming; Chen, Wei

    2018-07-01

    Brain energy metabolism relies predominantly on glucose and oxygen utilization to generate biochemical energy in the form of adenosine triphosphate (ATP). ATP is essential for maintaining basal electrophysiological activities in a resting brain and supporting evoked neuronal activity under an activated state. Studying complex neuroenergetic processes in the brain requires sophisticated neuroimaging techniques enabling noninvasive and quantitative assessment of cerebral energy metabolisms and quantification of metabolic rates. Recent state-of-the-art in vivo X-nuclear MRS techniques, including 2 H, 17 O and 31 P MRS have shown promise, especially at ultra-high fields, in the quest for understanding neuroenergetics and brain function using preclinical models and in human subjects under healthy and diseased conditions. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Polyalanine expansions drive a shift into α-helical clusters without amyloid-fibril formation.

    PubMed

    Polling, Saskia; Ormsby, Angelique R; Wood, Rebecca J; Lee, Kristie; Shoubridge, Cheryl; Hughes, James N; Thomas, Paul Q; Griffin, Michael D W; Hill, Andrew F; Bowden, Quill; Böcking, Till; Hatters, Danny M

    2015-12-01

    Polyglutamine (polyGln) expansions in nine human proteins result in neurological diseases and induce the proteins' tendency to form β-rich amyloid fibrils and intracellular deposits. Less well known are at least nine other human diseases caused by polyalanine (polyAla)-expansion mutations in different proteins. The mechanisms of how polyAla aggregates under physiological conditions remain unclear and controversial. We show here that aggregation of polyAla is mechanistically dissimilar to that of polyGln and hence does not exhibit amyloid kinetics. PolyAla assembled spontaneously into α-helical clusters with diverse oligomeric states. Such clustering was pervasive in cells irrespective of visible aggregate formation, and it disrupted the normal physiological oligomeric state of two human proteins natively containing polyAla: ARX and SOX3. This self-assembly pattern indicates that polyAla expansions chronically disrupt protein behavior by imposing a deranged oligomeric status.

  4. Roles of Diffusion Dynamics in Stem Cell Signaling and Three-Dimensional Tissue Development.

    PubMed

    McMurtrey, Richard J

    2017-09-15

    Recent advancements in the ability to construct three-dimensional (3D) tissues and organoids from stem cells and biomaterials have not only opened abundant new research avenues in disease modeling and regenerative medicine but also have ignited investigation into important aspects of molecular diffusion in 3D cellular architectures. This article describes fundamental mechanics of diffusion with equations for modeling these dynamic processes under a variety of scenarios in 3D cellular tissue constructs. The effects of these diffusion processes and resultant concentration gradients are described in the context of the major molecular signaling pathways in stem cells that both mediate and are influenced by gas and nutrient concentrations, including how diffusion phenomena can affect stem cell state, cell differentiation, and metabolic states of the cell. The application of these diffusion models and pathways is of vital importance for future studies of developmental processes, disease modeling, and tissue regeneration.

  5. An epidemiological modeling and data integration framework.

    PubMed

    Pfeifer, B; Wurz, M; Hanser, F; Seger, M; Netzer, M; Osl, M; Modre-Osprian, R; Schreier, G; Baumgartner, C

    2010-01-01

    In this work, a cellular automaton software package for simulating different infectious diseases, storing the simulation results in a data warehouse system and analyzing the obtained results to generate prediction models as well as contingency plans, is proposed. The Brisbane H3N2 flu virus, which has been spreading during the winter season 2009, was used for simulation in the federal state of Tyrol, Austria. The simulation-modeling framework consists of an underlying cellular automaton. The cellular automaton model is parameterized by known disease parameters and geographical as well as demographical conditions are included for simulating the spreading. The data generated by simulation are stored in the back room of the data warehouse using the Talend Open Studio software package, and subsequent statistical and data mining tasks are performed using the tool, termed Knowledge Discovery in Database Designer (KD3). The obtained simulation results were used for generating prediction models for all nine federal states of Austria. The proposed framework provides a powerful and easy to handle interface for parameterizing and simulating different infectious diseases in order to generate prediction models and improve contingency plans for future events.

  6. A closed recirculated sea-water system

    USGS Publications Warehouse

    1967-01-01

    Study of a virus disease in the chinook salmon (Oncorhynchus tshawytscha) necessitated the use of a marine environment to study the long range effects of the disease and to complete the life cycle of its etiologic agent. A closed recirculated sea-water system was designed for use under experimental laboratory conditions so that controlled studies of the disease could be made. As others may wish to do marine environment studies in the laboratory, the design and operation of our system are presented. Other systems currently in use have been described by Chin (1959), DeWitt and Salo (1960), McCrimmon and Berst (1966), and the authors of collected papers edited by Clark and Clark (1964). Preparatory to the design and construction of the system in use in this laboratory, visits were made to marine systems in use at the University of Washington's College of Fisheries, Seattle, -washington, and Friday Harbor Laboratory, San Juan Island, Washington; the Washington State Department of Fisheries' Point whitney Shellfish Laboratory, Brinnon, Washington; Humboldt State College, Arcata, California; and the Steinhart Aquarium of the California Academy of Science, San Francisco, California.

  7. CAVEOLINS AND LUNG FUNCTION

    PubMed Central

    Maniatis, Nikolaos A.; Chernaya, Olga; Shinin, Vasily; Minshall, Richard D.

    2012-01-01

    The primary function of the mammalian lung is to facilitate diffusion of oxygen to venous blood and to ventilate carbon dioxide produced by catabolic reactions within cells. However, it is also responsible for a variety of other important functions, including host defense and production of vasoactive agents to regulate not only systemic blood pressure, but also water, electrolyte and acid-base balance. Caveolin-1 is highly expressed in the majority of cell types in the lung, including epithelial, endothelial, smooth muscle, connective tissue cells, and alveolar macrophages. Deletion of caveolin-1 in these cells results in major functional aberrations, suggesting that caveolin-1 may be crucial to lung homeostasis and development. Furthermore, generation of mutant mice that under-express caveolin-1 results in severe functional distortion with phenotypes covering practically the entire spectrum of known lung diseases, including pulmonary hypertension, fibrosis, increased endothelial permeability, and immune defects. In this Chapter, we outline the current state of knowledge regarding caveolin-1-dependent regulation of pulmonary cell functions and discuss recent research findings on the role of caveolin-1 in various pulmonary disease states, including obstructive and fibrotic pulmonary vascular and inflammatory diseases. PMID:22411320

  8. Memory-induced nonlinear dynamics of excitation in cardiac diseases.

    PubMed

    Landaw, Julian; Qu, Zhilin

    2018-04-01

    Excitable cells, such as cardiac myocytes, exhibit short-term memory, i.e., the state of the cell depends on its history of excitation. Memory can originate from slow recovery of membrane ion channels or from accumulation of intracellular ion concentrations, such as calcium ion or sodium ion concentration accumulation. Here we examine the effects of memory on excitation dynamics in cardiac myocytes under two diseased conditions, early repolarization and reduced repolarization reserve, each with memory from two different sources: slow recovery of a potassium ion channel and slow accumulation of the intracellular calcium ion concentration. We first carry out computer simulations of action potential models described by differential equations to demonstrate complex excitation dynamics, such as chaos. We then develop iterated map models that incorporate memory, which accurately capture the complex excitation dynamics and bifurcations of the action potential models. Finally, we carry out theoretical analyses of the iterated map models to reveal the underlying mechanisms of memory-induced nonlinear dynamics. Our study demonstrates that the memory effect can be unmasked or greatly exacerbated under certain diseased conditions, which promotes complex excitation dynamics, such as chaos. The iterated map models reveal that memory converts a monotonic iterated map function into a nonmonotonic one to promote the bifurcations leading to high periodicity and chaos.

  9. Memory-induced nonlinear dynamics of excitation in cardiac diseases

    NASA Astrophysics Data System (ADS)

    Landaw, Julian; Qu, Zhilin

    2018-04-01

    Excitable cells, such as cardiac myocytes, exhibit short-term memory, i.e., the state of the cell depends on its history of excitation. Memory can originate from slow recovery of membrane ion channels or from accumulation of intracellular ion concentrations, such as calcium ion or sodium ion concentration accumulation. Here we examine the effects of memory on excitation dynamics in cardiac myocytes under two diseased conditions, early repolarization and reduced repolarization reserve, each with memory from two different sources: slow recovery of a potassium ion channel and slow accumulation of the intracellular calcium ion concentration. We first carry out computer simulations of action potential models described by differential equations to demonstrate complex excitation dynamics, such as chaos. We then develop iterated map models that incorporate memory, which accurately capture the complex excitation dynamics and bifurcations of the action potential models. Finally, we carry out theoretical analyses of the iterated map models to reveal the underlying mechanisms of memory-induced nonlinear dynamics. Our study demonstrates that the memory effect can be unmasked or greatly exacerbated under certain diseased conditions, which promotes complex excitation dynamics, such as chaos. The iterated map models reveal that memory converts a monotonic iterated map function into a nonmonotonic one to promote the bifurcations leading to high periodicity and chaos.

  10. Courts to look again at assisted dying law.

    PubMed

    Griffith, Richard

    2017-05-02

    A man with motor neurone disease has been granted permission by the Court of Appeal to seek judicial review the criminalisation of assisted dying under the Suicide Act 1961, section 2(1). In this article, Richard Griffith reviews the Court of Appeal's decision in R (on the application of Conway) v Secretary of State for Justice [2017] and considers arguments for and against decriminalising assisted dying.

  11. The Associations between Infant Homicide, Homicide, and Suicide Rates: An Analysis of World Health Organization and Centers for Disease Control Statistics

    ERIC Educational Resources Information Center

    Large, Matthew; Nielssen, Olav; Lackersteen, Steven; Smith, Glen

    2010-01-01

    Previous studies have found that rates of homicide of children aged under one (infant homicide) are associated with rates of suicide, but not with rates of homicide. Linear regression was used to examine associations among infant homicide, homicide, and suicide in samples of regions in the United States and other countries. Infant homicide rates…

  12. [Current problems in the laboratory control of louse-borne typhus infection in Ukraine].

    PubMed

    Klymchuk, M D

    1996-01-01

    Surveys designed to study spread of typhus infection (persistent form and Brill's disease), and state of laboratory diagnosis in Ukraine showed an important role the laboratory diagnosis plays in the system of epidemiological surveillance aimed at preventing epidemic typhus. Main trends of activities on perfection of the system of laboratory control of the infection under present-day conditions are outlined.

  13. Modeling the economic outcomes of immuno-oncology drugs: alternative model frameworks to capture clinical outcomes.

    PubMed

    Gibson, E J; Begum, N; Koblbauer, I; Dranitsaris, G; Liew, D; McEwan, P; Tahami Monfared, A A; Yuan, Y; Juarez-Garcia, A; Tyas, D; Lees, M

    2018-01-01

    Economic models in oncology are commonly based on the three-state partitioned survival model (PSM) distinguishing between progression-free and progressive states. However, the heterogeneity of responses observed in immuno-oncology (I-O) suggests that new approaches may be appropriate to reflect disease dynamics meaningfully. This study explored the impact of incorporating immune-specific health states into economic models of I-O therapy. Two variants of the PSM and a Markov model were populated with data from one clinical trial in metastatic melanoma patients. Short-term modeled outcomes were benchmarked to the clinical trial data and a lifetime model horizon provided estimates of life years and quality adjusted life years (QALYs). The PSM-based models produced short-term outcomes closely matching the trial outcomes. Adding health states generated increased QALYs while providing a more granular representation of outcomes for decision making. The Markov model gave the greatest level of detail on outcomes but gave short-term results which diverged from those of the trial (overstating year 1 progression-free survival by around 60%). Increased sophistication in the representation of disease dynamics in economic models is desirable when attempting to model treatment response in I-O. However, the assumptions underlying different model structures and the availability of data for health state mapping may be important limiting factors.

  14. Eczema prevalence in the United States: Data from the 2003 National Survey of Children’s Health

    PubMed Central

    Shaw, Tatyana E.; Currie, Gabriel P.; Koudelka, Caroline W.; Simpson, Eric L.

    2011-01-01

    Using the 2003 National Survey of Children’s Health (NSCH) sponsored by the federal Maternal and Child Health Bureau, we calculated prevalence estimates of eczema nationally and for each state among a nationally representative sample of 102,353 children 17 years of age and under. Our objective was to determine the national prevalence of eczema/atopic dermatitis in the United States pediatric population and to further examine geographic and demographic associations previously reported in other countries. Overall, 10.7% of children were reported to have a diagnosis of eczema in the last 12 months. Prevalence ranged from 8.7% to 18.1% between states and districts, with the highest prevalence reported in many of the East Coast states, as well as Nevada, Utah, and Idaho. After adjusting for confounders, metropolitan living was found to be a significant factor in predicting a higher disease prevalence with an OR of 1.67 (95% confidence interval of 1.19-2.35, p=0.008). Black race (OR 1.70, p=0.005) and education level in the household greater than high school (OR 1.61, p=0.004) were also significantly associated with a higher prevalence of eczema. The wide range of prevalence suggests social or environmental factors may influence disease expression. PMID:20739951

  15. Federally-Assisted Healthcare Coverage among Male State Prisoners with Chronic Health Problems.

    PubMed

    Rosen, David L; Grodensky, Catherine A; Holley, Tara K

    2016-01-01

    Prisoners have higher rates of chronic diseases such as substance dependence, mental health conditions and infectious disease, as compared to the general population. We projected the number of male state prisoners with a chronic health condition who at release would be eligible or ineligible for healthcare coverage under the Affordable Care Act (ACA). We used ACA income guidelines in conjunction with reported pre-arrest social security benefits and income from a nationally representative sample of prisoners to estimate the number eligible for healthcare coverage at release. There were 643,290 US male prisoners aged 18-64 with a chronic health condition. At release, 73% in Medicaid-expansion states would qualify for Medicaid or tax credits. In non-expansion states, 54% would qualify for tax credits, but 22% (n = 69,827) had incomes of ≤ 100% the federal poverty limit and thus would be ineligible for ACA-mediated healthcare coverage. These prisoners comprise 11% of all male prisoners with a chronic condition. The ACA was projected to provide coverage to most male state prisoners with a chronic health condition; however, roughly 70,000 fall in the "coverage gap" and may require non-routine care at emergency departments. Mechanisms are needed to secure coverage for this at risk group and address barriers to routine utilization of health services.

  16. Criticality in epidemiology

    NASA Astrophysics Data System (ADS)

    Stollenwerk, Nico; Jansen, Vincent A. A.

    For a long time criticality has been considered in epidemiological models. We review the body of theory developed over the last twenty five years for the simplest models. It is at first glance difficult to imagine that an epidemiological system operates at a very fine tuned critical state as opposed to any other parameter region. However, the advent of self-organized criticality has given hints in how to interpret large fluctuations observed in many natural systems including epidemiological systems. We show some scenarios where criticality has been observed (e.g., measles under vaccination) and where evolution towards a critical state can explain fluctuations (e.g., meningococcal disease.)

  17. Video Release: 47th Vice President of the United States Joseph R. Biden Jr. Speech at HUPO2017 Global Leadership Gala | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    The Human Proteome Organization (HUPO) has released a video of the keynote speech given by the 47th Vice President of the United States of America Joseph R. Biden Jr. at the HUPO2017 Global Leadership Gala. Under the gala theme “International Cooperation in the Fight Against Cancer,” Biden recognized cancer as a collection of related diseases, the importance of data sharing and harmonization, and the need for collaboration across scientific disciplines as inflection points in cancer research.

  18. Arterial Stiffness in Children: Pediatric Measurement and Considerations

    PubMed Central

    Savant, Jonathan D.; Furth, Susan L.; Meyers, Kevin E.C.

    2014-01-01

    Background Arterial stiffness is a natural consequence of aging, accelerated in certain chronic conditions, and predictive of cardiovascular events in adults. Emerging research suggests the importance of arterial stiffness in pediatric populations. Methods There are different indices of arterial stiffness. The present manuscript focuses on carotid-femoral pulse wave velocity and pulse wave analysis, although other methodologies are discussed. Also reviewed are specific measurement considerations for pediatric populations and the literature describing arterial stiffness in children with certain chronic conditions (primary hypertension, obesity, diabetes, chronic kidney disease, hypercholesterolemia, genetic syndromes involving vasculopathy, and solid organ transplant recipients). Conclusions The measurement of arterial stiffness in children is feasible and, under controlled conditions, can give accurate information about the underlying state of the arteries. This potentially adds valuable information about the functionality of the cardiovascular system in children with a variety of chronic diseases well beyond that of the brachial artery blood pressure. PMID:26587447

  19. Preeclampsia and the Future Risk of Hypertension: The Pregnant Evidence

    PubMed Central

    Garovic, Vesna D.; August, Phyllis

    2013-01-01

    Cardiovascular death rates continue to rise for women under age 55, underlying the importance of focusing on female-specific conditions that may increase cardiovascular risk, including pregnancy-related disorders. Hypertension complicates about 5–10% of pregnancies. Preeclampsia, a pregnancy-specific condition, is characterized by hypertension and proteinuria after 20 weeks of gestation and remains one of the major causes of maternal deaths in the United States. In addition, preeclampsia may have an impact on women’s health beyond their pregnancies, and has been associated with increased risks for future hypertension and cardiovascular disease, such as coronary heart disease and stroke. In this review, we discuss the evidence supporting the association between preeclampsia and future hypertension; possible mechanisms that underlie this association; current approach to women with a history of preeclampsia; and future research that is needed in this field in order to deliver optimal and timely medical care to the affected women. PMID:23397213

  20. Processes Underlying Rabies Virus Incursions across US-Canada Border as Revealed by Whole-Genome Phylogeography.

    PubMed

    Trewby, Hannah; Nadin-Davis, Susan A; Real, Leslie A; Biek, Roman

    2017-09-01

    Disease control programs aim to constrain and reduce the spread of infection. Human disease interventions such as wildlife vaccination play a major role in determining the limits of a pathogen's spatial distribution. Over the past few decades, a raccoon-specific variant of rabies virus (RRV) has invaded large areas of eastern North America. Although expansion into Canada has been largely prevented through vaccination along the US border, several outbreaks have occurred in Canada. Applying phylogeographic approaches to 289 RRV whole-genome sequences derived from isolates collected in Canada and adjacent US states, we examined the processes underlying these outbreaks. RRV incursions were attributable predominantly to systematic virus leakage of local strains across areas along the border where vaccination has been conducted but also to single stochastic events such as long-distance translocations. These results demonstrate the utility of phylogeographic analysis of pathogen genomes for understanding transboundary outbreaks.

  1. Vascular structural and functional changes: their association with causality in hypertension: models, remodeling and relevance.

    PubMed

    Lee, Robert Mkw; Dickhout, Jeffrey G; Sandow, Shaun L

    2017-04-01

    Essential hypertension is a complex multifactorial disease process that involves the interaction of multiple genes at various loci throughout the genome, and the influence of environmental factors such as diet and lifestyle, to ultimately determine long-term arterial pressure. These factors converge with physiological signaling pathways to regulate the set-point of long-term blood pressure. In hypertension, structural changes in arteries occur and show differences within and between vascular beds, between species, models and sexes. Such changes can also reflect the development of hypertension, and the levels of circulating humoral and vasoactive compounds. The role of perivascular adipose tissue in the modulation of vascular structure under various disease states such as hypertension, obesity and metabolic syndrome is an emerging area of research, and is likely to contribute to the heterogeneity described in this review. Diversity in structure and related function is the norm, with morphological changes being causative in some beds and states, and in others, a consequence of hypertension. Specific animal models of hypertension have advantages and limitations, each with factors influencing the relevance of the model to the human hypertensive state/s. However, understanding the fundamental properties of artery function and how these relate to signalling mechanisms in real (intact) tissues is key for translating isolated cell and model data to have an impact and relevance in human disease etiology. Indeed, the ultimate aim of developing new treatments to correct vascular dysfunction requires understanding and recognition of the limitations of the methodologies used.

  2. [Exercise for prevention of osteoporosis and other lifestyle-related diseases].

    PubMed

    Suzuki, Takao

    2011-05-01

    The prevalence of lifestyle-related diseases including hypertension, dyslipidemia (hyperlipidemia) and diabetes increases with aging, and all these conditions are risk factors of arteriosclerotic diseases such as cerebrovascular event (stroke) and myocardial infarction. The term "metabolic domino" has been used to describe the collective concept of the development and progression of these lifestyle-related diseases, the sequence of events, and the progression process of complications. Like the first tile of a domino toppling game, undesirable lifestyle such as overeating and underexercising first triggers obesity, and is followed in succession by onset of an insulin resistance state (underlied by a genetic background indigenous to Japanese) , hypertension, hyperlipidemia, and further postprandial hyperglycemia (the pre-diabetic state) , the so-called metabolic syndrome, at around the same time. On the other hand, apart from the other lifestyle-related diseases, the prevalence of osteoporosis also increases rapidly accompanying aging. Osteoporosis is known to be strongly related to disorders due to the metabolic domino such as arteriosclerosis and vascular calcification, and a new disease category called "osteo-vascular interaction" has attracted attention recently. Regarding "osteo-vascular interaction" , a close relation between bone density loss or osteoporotic changes and vascular lesion-associated lifestyle-related diseases such as hypertension, dyslipidemia and diabetes has been reported. Therefore, as a common preventive factor for bone mass loss or osteoporosis and lifestyle-related diseases including hypertension, dyslipidemia and diabetes (osteo-vascular interaction) , exercise has been recognized anew as an important non-pharmaceutical therapy that should take top priority. This article overviews the evidence of exercise therapy for the prevention of osteoporosis and other lifestyle-related diseases, from the viewpoint of health promotion, especially of the skeletal system (motor system) .

  3. Decision analytic models for Alzheimer's disease: state of the art and future directions.

    PubMed

    Cohen, Joshua T; Neumann, Peter J

    2008-05-01

    Decision analytic policy models for Alzheimer's disease (AD) enable researchers and policy makers to investigate questions about the costs and benefits of a wide range of existing and potential screening, testing, and treatment strategies. Such models permit analysts to compare existing alternatives, explore hypothetical scenarios, and test the strength of underlying assumptions in an explicit, quantitative, and systematic way. Decision analytic models can best be viewed as complementing clinical trials both by filling knowledge gaps not readily addressed by empirical research and by extrapolating beyond the surrogate markers recorded in a trial. We identified and critiqued 13 distinct AD decision analytic policy models published since 1997. Although existing models provide useful insights, they also have a variety of limitations. (1) They generally characterize disease progression in terms of cognitive function and do not account for other distinguishing features, such as behavioral symptoms, functional performance, and the emotional well-being of AD patients and caregivers. (2) Many describe disease progression in terms of a limited number of discrete states, thus constraining the level of detail that can be used to characterize both changes in patient status and the relationships between disease progression and other factors, such as residential status, that influence outcomes of interest. (3) They have focused almost exclusively on evaluating drug treatments, thus neglecting other disease management strategies and combinations of pharmacologic and nonpharmacologic interventions. Future AD models should facilitate more realistic and compelling evaluations of various interventions to address the disease. An improved model will allow decision makers to better characterize the disease, to better assess the costs and benefits of a wide range of potential interventions, and to better evaluate the incremental costs and benefits of specific interventions used in conjunction with other disease management strategies.

  4. 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

  5. Nanostructured TiO2 surfaces promote polarized activation of microglia, but not astrocytes, toward a proinflammatory profile

    NASA Astrophysics Data System (ADS)

    de Astis, Silvia; Corradini, Irene; Morini, Raffaella; Rodighiero, Simona; Tomasoni, Romana; Lenardi, Cristina; Verderio, Claudia; Milani, Paolo; Matteoli, Michela

    2013-10-01

    Activation of glial cells, including astrocytes and microglia, has been implicated in the inflammatory responses underlying brain injury and neurodegenerative diseases including Alzheimer's and Parkinson's diseases. The classic activation state (M1) is characterized by high capacity to present antigens, high production of nitric oxide (NO) and reactive oxygen species (ROS) and proinflammatory cytokines. Classically activated cells act as potent effectors that drive the inflammatory response and may mediate detrimental effects on neural cells. The second phenotype (M2) is an alternative, apparently beneficial, activation state, more related to a fine tuning of inflammation, scavenging of debris, promotion of angiogenesis, tissue remodeling and repair. Specific environmental chemical signals are able to induce these different polarization states. We provide here evidence that nanostructured substrates are able, exclusively in virtue of their physical properties, to push microglia toward the proinflammatory activation phenotype, with an efficacy which reflects the graded nanoscale rugosity. The acquisition of a proinflammatory phenotype appears specific for microglia and not astrocytes, indicating that these two cell types, although sharing common innate immune responses, respond differently to external physical stimuli.

  6. Cryptococcus gattii infections in multiple states outside the US Pacific Northwest.

    PubMed

    Harris, Julie R; Lockhart, Shawn R; Sondermeyer, Gail; Vugia, Duc J; Crist, Matthew B; D'Angelo, Melissa Tobin; Sellers, Brenda; Franco-Paredes, Carlos; Makvandi, Monear; Smelser, Chad; Greene, John; Stanek, Danielle; Signs, Kimberly; Nett, Randall J; Chiller, Tom; Park, Benjamin J

    2013-10-01

    Clonal VGII subtypes (outbreak strains) of Cryptococcus gattii have caused an outbreak in the US Pacific Northwest since 2004. Outbreak-associated infections occur equally in male and female patients (median age 56 years) and usually cause pulmonary disease in persons with underlying medical conditions. Since 2009, a total of 25 C. gattii infections, 23 (92%) caused by non-outbreak strain C. gattii, have been reported from 8 non-Pacific Northwest states. Sixteen (64%) patients were previously healthy, and 21 (84%) were male; median age was 43 years (range 15-83 years). Ten patients who provided information reported no past-year travel to areas where C. gattii is known to be endemic. Nineteen (76%) patients had central nervous system infections; 6 (24%) died. C. gattii infection in persons without exposure to known disease-endemic areas suggests possible endemicity in the United States outside the outbreak-affected region; these infections appear to differ in clinical and demographic characteristics from outbreak-associated C. gattii. Clinicians outside the outbreak-affected areas should be aware of locally acquired C. gattii infection and its varied signs and symptoms.

  7. Cryptococcus gattii Infections in Multiple States Outside the US Pacific Northwest

    PubMed Central

    Lockhart, Shawn R.; Sondermeyer, Gail; Vugia, Duc J.; Crist, Matthew B.; D’Angelo, Melissa Tobin; Sellers, Brenda; Franco-Paredes, Carlos; Makvandi, Monear; Smelser, Chad; Greene, John; Stanek, Danielle; Signs, Kimberly; Nett, Randall J.; Chiller, Tom; Park, Benjamin J.

    2013-01-01

    Clonal VGII subtypes (outbreak strains) of Cryptococcus gattii have caused an outbreak in the US Pacific Northwest since 2004. Outbreak-associated infections occur equally in male and female patients (median age 56 years) and usually cause pulmonary disease in persons with underlying medical conditions. Since 2009, a total of 25 C. gattii infections, 23 (92%) caused by non–outbreak strain C. gattii, have been reported from 8 non–Pacific Northwest states. Sixteen (64%) patients were previously healthy, and 21 (84%) were male; median age was 43 years (range 15–83 years). Ten patients who provided information reported no past-year travel to areas where C. gattii is known to be endemic. Nineteen (76%) patients had central nervous system infections; 6 (24%) died. C. gattii infection in persons without exposure to known disease-endemic areas suggests possible endemicity in the United States outside the outbreak-affected region; these infections appear to differ in clinical and demographic characteristics from outbreak-associated C. gattii. Clinicians outside the outbreak-affected areas should be aware of locally acquired C. gattii infection and its varied signs and symptoms. PMID:24050410

  8. The contemporary management of prostate cancer in the United States: lessons from the cancer of the prostate strategic urologic research endeavor (CapSURE), a national disease registry.

    PubMed

    Cooperberg, Matthew R; Broering, Jeanette M; Litwin, Mark S; Lubeck, Deborah P; Mehta, Shilpa S; Henning, James M; Carroll, Peter R

    2004-04-01

    The epidemiology and treatment of prostate cancer have changed dramatically in the prostate specific antigen era. A large disease registry facilitates the longitudinal observation of trends in disease presentation, management and outcomes. The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) is a national disease registry of more than 10000 men with prostate cancer accrued at 31 primarily community based sites across the United States. Demographic, clinical, quality of life and resource use variables are collected on each patient. We reviewed key findings from the data base in the last 8 years in the areas of disease management trends, and oncological and quality of life outcomes. Prostate cancer is increasingly diagnosed with low risk clinical characteristics. With time patients have become less likely to receive pretreatment imaging tests, less likely to pursue watchful waiting and more likely to receive brachytherapy or hormonal therapy. Relatively few patients treated with radical prostatectomy in the database are under graded or under staged before surgery, whereas the surgical margin rate is comparable to that in academic series. CaPSURE data confirm the usefulness of percent positive biopsies in risk assessment and they have further been used to validate multiple preoperative nomograms. CaPSURE results strongly affirm the necessity of patient reported quality of life assessment. Multiple studies have compared the quality of life impact of various treatment options, particularly in terms of urinary and sexual function, and bother. The presentation and management of prostate cancer have changed substantially in the last decade. CaPSURE will continue to track these trends as well as oncological and quality of life outcomes, and will continue to be an invaluable resource for the study of prostate cancer at the national level.

  9. Introduction of a second dose of measles in national immunization program in India: a major step towards eradication.

    PubMed

    Verma, Ramesh; Khanna, Pardeep; Bairwa, Mohan; Chawla, Suraj; Prinja, Shankar; Rajput, Meena

    2011-10-01

    Measles is a highly infectious, acute respiratory illness that is caused by a virus of the genus Morbillivirus. The disease infects nearly 30 million children each year, and deaths usually occur from complications related to pneumonia, diarrhea and malnutrition. A systematic review of published Indian literature depicts the median case fatality ratio (CFR) of measles to be 1.6%. Through immunization, measles deaths dropped a remarkable 78% from 733,000 in 2000 to 164,000 in 2008. As of 2008, 192 of 193 Member States of WHO use 2 doses of measles vaccine in their national immunization programs, India being the only exception. The Millennium Development Goal (MDG) 4 aims to reduce by two-thirds between 1990 and 2015 the under-five mortality rate (U5MR) in the world. Per the draft comprehensive Multi Year Strategic Plan (cMYP, 2010–17) for immunization of India, the country aims to reduce measles-related mortality by 90% by 2013 when compared to 2000. As recommended by the National Technical Advisory Group on Immunization (NTAGI), the implementation strategy of the second dose of measles vaccine at the state level is determined by the underlying performance of the routine immunization program. The second dose in the national immunization schedule gives extra immunity against measles infection that renders children more susceptible to secondary pneumonia and diarrheal diseases, which are the primary causes of under-5 child mortality in India.

  10. Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

    PubMed

    Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

    2017-09-01

    Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

  11. The mitochondrial and kidney disease phenotypes of kd/kd mice under germfree conditions

    PubMed Central

    Hallman, Troy M.; Peng, Min; Meade, Ray; Hancock, Wayne W.; Madaio, Michael P.; Gasser, David L.

    2008-01-01

    Interstitial nephritis occurs spontaneously in kd/kd mice, but the mechanisms leading to this disease have not been fully elucidated. The earliest manifestation of a phenotype is the appearance of ultrastructural defects in the mitochondria of mice as young as 42 days of age. To examine the influence of the environment on the phenotype, homozygous B6.kd/kd mice were transferred from specific pathogen-free (SPF) conditions to a germfree (GF) environment, and the development of the disease was observed. The GF state resulted in a highly significant reduction in the frequency of tubulointerstitial nephritis. In addition, GF conditions markedly reduced the appearance of the mitochondrial phenotype, with no sign of mitochondrial abnormalities in GF mice of up to 155 days of age. These results suggest that environmental factors are involved in the progression of all known manifestations of this disease phenotype. PMID:16337774

  12. Antiphospholipid Antibody Syndrome Associated with Graves’ Disease Presenting As Inferior Vena Cava Thrombosis with Bilateral Lower Limb DVT

    PubMed Central

    Jain, Ankur

    2014-01-01

    We report a case of a 60-year-old lady who presented with bilateral lower limb swelling and a thyroid swelling with clinical features consistent with thyrotoxicosis. Investigations revealed the presence of a thrombus in bilateral external, internal iliac veins, and inferior vena cava extending up to its infrahepatic part. Hormone profile and radioiodine uptake scan confirmed the diagnosis of Graves’ disease. Further workup revealed the presence of antiphospholipid antibodies (confirmed after a repeat test at 12 weeks). The patient was treated with antithyroid drugs and anticoagulants. The patient improved with normalization of thyroid function and partial recanalization of the infrahepatic part of inferior vena cava. Hyperthyroidism has been implicated as a potential hypercoagulable state; however, the association of Graves’ disease with antiphospholipid antibody syndrome is limited to isolated case reports. This case highlights a new mechanism underlying hypercoagulability associated with Graves’ disease. PMID:24812529

  13. Biomarker-guided translation of brain imaging into disease pathway models

    PubMed Central

    Younesi, Erfan; Hofmann-Apitius, Martin

    2013-01-01

    The advent of state-of-the-art brain imaging technologies in recent years and the ability of such technologies to provide high-resolution information at both structural and functional levels has spawned large efforts to introduce novel non-invasive imaging biomarkers for early prediction and diagnosis of brain disorders; however, their utility in both clinic and drug development at their best resolution remains limited to visualizing and monitoring disease progression. Given the fact that efficient translation of valuable information embedded in brain scans into clinical application is of paramount scientific and public health importance, a strategy is needed to bridge the current gap between imaging and molecular biology, particularly in neurodegenerative diseases. As an attempt to address this issue, we present a novel computational method to link readouts of imaging biomarkers to their underlying molecular pathways with the aim of guiding clinical diagnosis, prognosis and even target identification in drug discovery for Alzheimer's disease. PMID:24287435

  14. Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

    PubMed Central

    DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

  15. Biomarker for early renal microvascular and diabetic kidney diseases.

    PubMed

    Futrakul, Narisa; Futrakul, Prasit

    2017-11-01

    Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

  16. Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases

    PubMed Central

    Kalyani, Rita Rastogi; Corriere, Mark; Ferrucci, Luigi

    2014-01-01

    The term sarcopenia refers to the loss of muscle mass that occurs with ageing. On the basis of study results showing that muscle mass is only moderately related to functional outcomes, international working groups have proposed that loss of muscle strength or physical function should also be included in the definition. Irrespective of how sarcopenia is defined, both low muscle mass and poor muscle strength are clearly highly prevalent and important risk factors for disability and potentially mortality in individuals as they age. Many chronic diseases, in addition to ageing, could also accelerate decrease of muscle mass and strength, and this effect could be a main underlying mechanism by which chronic diseases cause physical disability. In this Review, we address both age-related and disease-related muscle loss, with a focus on diabetes and obesity but including other disease states, and potential common mechanisms and treatments. Development of treatments for age-related and disease-related muscle loss might improve active life expectancy in older people, and lead to substantial health-care savings and improved quality of life. PMID:24731660

  17. Protecting the waters of Wisconsin from microbiological threats.

    PubMed

    Standridge, Jon

    2003-01-01

    Wisconsin is blessed with an abundance of high quality water that has played a significant role in the economic and social development of the state. The quality of life for Wisconsinites is often at least partially defined by pristine inland lakes, a portion of the Great Lakes shoreline, or great-tasting well water. While no one likes to associate water with disease, especially waters like those we enjoy in Wisconsin, the historical reality is that there is a strong connection. Until the 1920s, intestinal diseases such as typhoid fever and cholera often spread through water and were a leading cause of death in the United States. While easy access to modern medical care combined with improved water treatment technologies have greatly decreased waterborne disease, the microbiology of Wisconsin's waters still deserves continued vigilance and attention. The World Health Organization currently estimates that, on a global basis, 4 billion annual cases of waterborne diarrhea result in more than 2 million deaths per year--the equivalent of 20 jumbo jet crashes per day. Most of these deaths are in children under 5 years of age. The daily global death toll from waterborne disease is at least 1000 times greater than from the Severe Acute Respiratory Syndrome epidemic that recently made headline news. Waterborne disease is not just a problem in underdeveloped countries. Scientists who study disease transmission believe that 10%-30% of the vomiting and diarrhea illness in North America, including Wisconsin, may be acquired from water.

  18. Prognosis parameters and polarimetric properties of erythrocytes of the patients suffering from arterial hypertension and coronary heart disease at various patterns of left ventricular remodeling

    NASA Astrophysics Data System (ADS)

    Ivaschuk, Oleg I.; Kolomoiets, M. Y.; Mikhaliev, K. O.; Chursina, T. Ya.

    2011-09-01

    The results of examination of 35 arterial hypertension and coronary heart disease patients are presented. The clinical, paraclinical and echocardiographic examinations were performed, and the parameters of prognosis (survival) according to Seattle Heart Failure Model, as well as the optical (polarimetric) properties of erythrocytic suspension were determined. The group of patients under examination was stratified by patterns of remodeling of left ventricle (LV). It was determined that increasing of anisotropy of erythrocytic suspension along LV remodeling patterns continuum correlates with aggravation of structural and functional state of LV and is associated with unfavorable prognosis.

  19. Successful Treatment of Disseminated Cryptococcal Infection in a Pediatric Acute Lymphoblastic Leukemia Patient During Induction

    PubMed Central

    Heath, Jessica L.; Yin, Dwight E.; Wechsler, Daniel S.; Turner, David A.

    2015-01-01

    Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between anti-fungal and anti-neoplastic therapy. This balance is particularly important early in the course of leukemia, since both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy. PMID:22258349

  20. From hemobiology to vascular disease: a review of the potential of gliclazide to influence the pathogenesis of diabetic vascular disease.

    PubMed

    Jennings, P E

    1994-01-01

    Patients with type II diabetes commonly die from thrombotic vascular disease. Large vessel occlusion due to thrombosis or atherosclerotic stenosis is a process accelerated by diabetes and results in premature death. Diabetic small vessel disease, with its unique microangiopathic process, underlies many of the large vessel changes as well as causing retinopathy and nephropathy. The microangiopathic changes produce a prothrombotic tendency that has been widely reported in type II diabetes. There is reduced endothelial cell production of prostacyclin and the activators of fibrinolysis, together with increased platelet reactivity. In addition, there is increased lipid peroxidation and oxidative stress due to excess free-radical activity and impaired antioxidant defenses particularly in the presence of microvascular disease. The development of many of these abnormalities is associated with poor long-term glycemic control. However, the changes are also seen in atherosclerosis in nondiabetic patients where the progression of the disease can be modified by antiplatelet agents and antioxidants. The process of vascular damage is accelerated by diabetes, often due to co-existing disease and aging, although it is not clear that improvement in long-term glycemic control by lowering blood glucose levels to near to the nondiabetic state reduces the development of small and large vessel disease. Although the biochemical mechanism underlying this observation remains uncertain, protein glycosylation and increased platelet reactivity are implicated and interrelated. Increased oxidative stress due to excess free-radical activity may be central to diabetic vascular disease as endothelial cell damage, lipoprotein oxidation, modification of both platelet reactivity and arachidonic acid cascade are all properties of free radicals and their reaction products lipid peroxides.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Brightness-preserving fuzzy contrast enhancement scheme for the detection and classification of diabetic retinopathy disease.

    PubMed

    Datta, Niladri Sekhar; Dutta, Himadri Sekhar; Majumder, Koushik

    2016-01-01

    The contrast enhancement of retinal image plays a vital role for the detection of microaneurysms (MAs), which are an early sign of diabetic retinopathy disease. A retinal image contrast enhancement method has been presented to improve the MA detection technique. The success rate on low-contrast noisy retinal image analysis shows the importance of the proposed method. Overall, 587 retinal input images are tested for performance analysis. The average sensitivity and specificity are obtained as 95.94% and 99.21%, respectively. The area under curve is found as 0.932 for the receiver operating characteristics analysis. The classifications of diabetic retinopathy disease are also performed here. The experimental results show that the overall MA detection method performs better than the current state-of-the-art MA detection algorithms.

  2. Heparin-induced thrombocytopenia

    PubMed Central

    2017-01-01

    Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets and monocytes to propagate a hypercoagulable state culminating in life-threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies develop commonly after heparin exposure, but only a subset of sensitized patients progress to life-threatening complications of thrombocytopenia and thrombosis. Recent scientific developments have clarified mechanisms underlying PF4/heparin immunogenicity, disease susceptibility, and clinical manifestations of disease. Insights from clinical and laboratory findings have also been recently harnessed for disease prevention. This review will summarize our current understanding of HIT by reviewing pathogenesis, essential clinical and laboratory features, and management. PMID:28416511

  3. Noncoding RNAs and chronic inflammation: Micro‐managing the fire within

    PubMed Central

    Alexander, Margaret

    2015-01-01

    Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age‐associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets. Copyright Line: © 2015 The Authors BioEssays Published by Wiley‐VCH Verlag GmbH & Co. KGaA. PMID:26249326

  4. REMEDIAL APPLICATIONS OF EXOSOMES IN CANCER, INFECTIONS AND DIABETES.

    PubMed

    Wang, Qianhuai; Ding, Xiaoqing; Zhen, Fei; Ma, Jianwei; Meng, Fanxing

    2017-03-01

    Different cell types under normal and diseased states constantly secrete numerous membrane vesicles including exosomes into extracellular space wkich can be isolated from various biological fluids and cell culture supernatants. Exosomal diameter ranges between 40-100 nm. In current research, exosomes are being exploited as biomarkers for pathological diagnosis and potential remedy against various disease conditions such as infections and autoimmune disorders. In cancer immunotherapy, exosomes have promisingly been employed due to the identical immunogenic antigens of exosomes produced by neoplastic cells and the originating tissues. Antigen-specific T-cell activation and immunomodulatory activity is observed to be performed by exosomes isolated from tumor and dendritic cells (DCs). However, more research is still required to uncover the realistic uses of exosomes, particularly as drug delivery tool in autoimmune diseases, cancers and diabetes.

  5. Surveillance for Lyme Disease - United States, 2008-2015.

    PubMed

    Schwartz, Amy M; Hinckley, Alison F; Mead, Paul S; Hook, Sarah A; Kugeler, Kiersten J

    2017-11-10

    Lyme disease is the most commonly reported vectorborne disease in the United States but is geographically focal. The majority of Lyme disease cases occur in the Northeast, mid-Atlantic, and upper Midwest regions. Lyme disease can cause varied clinical manifestations, including erythema migrans, arthritis, facial palsy, and carditis. Lyme disease occurs most commonly among children and older adults, with a slight predominance among males. 2008-2015. Lyme disease has been a nationally notifiable condition in the United States since 1991. Possible Lyme disease cases are reported to local and state health departments by clinicians and laboratories. Health department staff conduct case investigations to classify cases according to the national surveillance case definition. Those that qualify as confirmed or probable cases of Lyme disease are reported to CDC through the National Notifiable Diseases Surveillance System. States with an average annual incidence during this reporting period of ≥10 confirmed Lyme disease cases per 100,000 population were classified as high incidence. States that share a border with those states or that are located between areas of high incidence were classified as neighboring states. All other states were classified as low incidence. During 2008-2015, a total of 275,589 cases of Lyme disease were reported to CDC (208,834 confirmed and 66,755 probable). Although most cases continue to be reported from states with high incidence in the Northeast, mid-Atlantic, and upper Midwest regions, case counts in most of these states have remained stable or decreased during the reporting period. In contrast, case counts have increased in states that neighbor those with high incidence. Overall, demographic characteristics associated with confirmed cases were similar to those described previously, with a slight predominance among males and a bimodal age distribution with peaks among young children and older adults. Yet, among the subset of cases reported from states with low incidence, infection occurred more commonly among females and older adults. In addition, probable cases occurred more commonly among females and with a higher modal age than confirmed cases. Lyme disease continues to be the most commonly reported vectorborne disease in the United States. Although concentrated in historically high-incidence areas, the geographic distribution is expanding into neighboring states. The trend of stable to decreasing case counts in many states with high incidence could be a result of multiple factors, including actual stabilization of disease incidence or artifact due to modifications in reporting practices employed by some states to curtail the resource burden associated with Lyme disease surveillance. This report highlights the continuing public health challenge of Lyme disease in states with high incidence and demonstrates its emergence in neighboring states that previously experienced few cases. Educational efforts should be directed accordingly to facilitate prevention, early diagnosis, and appropriate treatment. As Lyme disease emerges in neighboring states, clinical suspicion of Lyme disease in a patient should be based on local experience rather than incidence cutoffs used for surveillance purposes. A diagnosis of Lyme disease should be considered in patients with compatible clinical signs and a history of potential exposure to infected ticks, not only in states with high incidence but also in areas where Lyme disease is known to be emerging. These findings underscore the ongoing need to implement personal prevention practices routinely (e.g., application of insect repellent and inspection for and removal of ticks) and to develop other effective interventions.

  6. Surveillance for Lyme Disease — United States, 2008–2015

    PubMed Central

    Schwartz, Amy M.; Hinckley, Alison F.; Mead, Paul S.; Hook, Sarah A.

    2017-01-01

    Problem/Condition Lyme disease is the most commonly reported vectorborne disease in the United States but is geographically focal. The majority of Lyme disease cases occur in the Northeast, mid-Atlantic, and upper Midwest regions. Lyme disease can cause varied clinical manifestations, including erythema migrans, arthritis, facial palsy, and carditis. Lyme disease occurs most commonly among children and older adults, with a slight predominance among males. Reporting Period 2008–2015. Description of System Lyme disease has been a nationally notifiable condition in the United States since 1991. Possible Lyme disease cases are reported to local and state health departments by clinicians and laboratories. Health department staff conduct case investigations to classify cases according to the national surveillance case definition. Those that qualify as confirmed or probable cases of Lyme disease are reported to CDC through the National Notifiable Diseases Surveillance System. States with an average annual incidence during this reporting period of ≥10 confirmed Lyme disease cases per 100,000 population were classified as high incidence. States that share a border with those states or that are located between areas of high incidence were classified as neighboring states. All other states were classified as low incidence. Results During 2008–2015, a total of 275,589 cases of Lyme disease were reported to CDC (208,834 confirmed and 66,755 probable). Although most cases continue to be reported from states with high incidence in the Northeast, mid-Atlantic, and upper Midwest regions, case counts in most of these states have remained stable or decreased during the reporting period. In contrast, case counts have increased in states that neighbor those with high incidence. Overall, demographic characteristics associated with confirmed cases were similar to those described previously, with a slight predominance among males and a bimodal age distribution with peaks among young children and older adults. Yet, among the subset of cases reported from states with low incidence, infection occurred more commonly among females and older adults. In addition, probable cases occurred more commonly among females and with a higher modal age than confirmed cases. Interpretation Lyme disease continues to be the most commonly reported vectorborne disease in the United States. Although concentrated in historically high-incidence areas, the geographic distribution is expanding into neighboring states. The trend of stable to decreasing case counts in many states with high incidence could be a result of multiple factors, including actual stabilization of disease incidence or artifact due to modifications in reporting practices employed by some states to curtail the resource burden associated with Lyme disease surveillance. Public Health Action This report highlights the continuing public health challenge of Lyme disease in states with high incidence and demonstrates its emergence in neighboring states that previously experienced few cases. Educational efforts should be directed accordingly to facilitate prevention, early diagnosis, and appropriate treatment. As Lyme disease emerges in neighboring states, clinical suspicion of Lyme disease in a patient should be based on local experience rather than incidence cutoffs used for surveillance purposes. A diagnosis of Lyme disease should be considered in patients with compatible clinical signs and a history of potential exposure to infected ticks, not only in states with high incidence but also in areas where Lyme disease is known to be emerging. These findings underscore the ongoing need to implement personal prevention practices routinely (e.g., application of insect repellent and inspection for and removal of ticks) and to develop other effective interventions. PMID:29120995

  7. Diarrheal diseases and hospitalization of children under five years of age according to population-based surveys in the State of Pernambuco, Brazil, in the years 1997 and 2006.

    PubMed

    Vasconcelos, Maria Josemere Oliveira Borba; Rissin, Anete; Figueiroa, José Natal; Lira, Pedro Israel Cabral de; Batista Filho, Malaquias

    2018-03-01

    The scope of this paper was to assess the temporal and geographical trends of diarrhea and its implications on the demands of hospitalizations of children under five years of age in the state of Pernambuco in 1997 and 2006. Databases of two population-based surveys were assessed with probabilistic samples of 2078 children (1997) and 1650 children (2006) evaluated in 18 municipalities of Pernambuco, including the Metropolitan Region of Recife, Urban Interior and Rural Interior. Prevalence was considered to involve the occurrence of cases on the day or in the two weeks prior to the interview and as admissions, service cases with minimal hospital stay of 24 hours in the period, covering up to one year before the interview. The prevalence of diarrhea in Pernambuco had a statistically non-significant decline (19.8% to 18.1%; p = 0.192). However, a statistically-significant reduction was observed (16.9% to 10.5%; p = 0.003) in the Metropolitan Region of Recife. The number of admissions increased by more than double (2.7% to 5.5% in the State and from 1.6% to 3.8% within the Metropolitan Region of Recife), in contrast with national trends. Therefore, diarrhea in the State appears as the main component of the demands of pediatric hospitalizations during the period under scrutiny.

  8. Projections of the current and future disease burden of hepatitis C virus infection in Malaysia.

    PubMed

    McDonald, Scott A; Dahlui, Maznah; Mohamed, Rosmawati; Naning, Herlianna; Shabaruddin, Fatiha Hana; Kamarulzaman, Adeeba

    2015-01-01

    The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods. An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed. In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039. The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia.

  9. Projections of the Current and Future Disease Burden of Hepatitis C Virus Infection in Malaysia

    PubMed Central

    McDonald, Scott A.; Dahlui, Maznah; Mohamed, Rosmawati; Naning, Herlianna; Shabaruddin, Fatiha Hana; Kamarulzaman, Adeeba

    2015-01-01

    Background The prevalence of hepatitis C virus (HCV) infection in Malaysia has been estimated at 2.5% of the adult population. Our objective, satisfying one of the directives of the WHO Framework for Global Action on Viral Hepatitis, was to forecast the HCV disease burden in Malaysia using modelling methods. Methods An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed. Results In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039. Conclusions The HCV-related disease burden is already high and is forecast to rise steeply over the coming decades under current levels of antiviral treatment. Increased governmental resources to improve HCV screening and treatment rates and to reduce transmission are essential to address the high projected HCV disease burden in Malaysia. PMID:26042425

  10. Automated Assessment of Existing Patient's Revised Cardiac Risk Index Using Algorithmic Software.

    PubMed

    Hofer, Ira S; Cheng, Drew; Grogan, Tristan; Fujimoto, Yohei; Yamada, Takashige; Beck, Lauren; Cannesson, Maxime; Mahajan, Aman

    2018-05-25

    Previous work in the field of medical informatics has shown that rules-based algorithms can be created to identify patients with various medical conditions; however, these techniques have not been compared to actual clinician notes nor has the ability to predict complications been tested. We hypothesize that a rules-based algorithm can successfully identify patients with the diseases in the Revised Cardiac Risk Index (RCRI). Patients undergoing surgery at the University of California, Los Angeles Health System between April 1, 2013 and July 1, 2016 and who had at least 2 previous office visits were included. For each disease in the RCRI except renal failure-congestive heart failure, ischemic heart disease, cerebrovascular disease, and diabetes mellitus-diagnosis algorithms were created based on diagnostic and standard clinical treatment criteria. For each disease state, the prevalence of the disease as determined by the algorithm, International Classification of Disease (ICD) code, and anesthesiologist's preoperative note were determined. Additionally, 400 American Society of Anesthesiologists classes III and IV cases were randomly chosen for manual review by an anesthesiologist. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were determined using the manual review as a gold standard. Last, the ability of the RCRI as calculated by each of the methods to predict in-hospital mortality was determined, and the time necessary to run the algorithms was calculated. A total of 64,151 patients met inclusion criteria for the study. In general, the incidence of definite or likely disease determined by the algorithms was higher than that detected by the anesthesiologist. Additionally, in all disease states, the prevalence of disease was always lowest for the ICD codes, followed by the preoperative note, followed by the algorithms. In the subset of patients for whom the records were manually reviewed, the algorithms were generally the most sensitive and the ICD codes the most specific. When computing the modified RCRI using each of the methods, the modified RCRI from the algorithms predicted in-hospital mortality with an area under the receiver operating characteristic curve of 0.70 (0.67-0.73), which compared to 0.70 (0.67-0.72) for ICD codes and 0.64 (0.61-0.67) for the preoperative note. On average, the algorithms took 12.64 ± 1.20 minutes to run on 1.4 million patients. Rules-based algorithms for disease in the RCRI can be created that perform with a similar discriminative ability as compared to physician notes and ICD codes but with significantly increased economies of scale.

  11. Derivation of vascular endothelial cells from human embryonic stem cells under GMP-compliant conditions: towards clinical studies in ischaemic disease.

    PubMed

    Kaupisch, A; Kennedy, L; Stelmanis, V; Tye, B; Kane, N M; Mountford, J C; Courtney, A; Baker, A H

    2012-10-01

    Revascularisation of ischaemic tissue remains an area of substantial unmet clinical need in cardiovascular disease. Strategies to induce therapeutic angiogenesis are therefore attractive. Our recent focus has been on human embryonic stem cell (hESC) strategies since hESC can be maintained in a pluripotent state or differentiated into any desired cell type, including endothelial cells (EC), under defined differentiation culture conditions. We recently published a protocol for non-good manufacturing practice (GMP) feeder- and serum-free hESC-EC-directed monolayer differentiation to vascular EC demonstrating the potential to generate hESC-derived EC in a GMP-compliant manner suitable for use in clinical trials. In this study we modified that laboratory protocol to GMP compliance. EC production was confirmed by flow cytometry, qRT-PCR and production of vascular structures in Matrigel®, yielding approximately 30 % mature VE-cadherin(+)/PECAM-1(+) cells using the GMP-compliant hESC line RC13. In conclusion, we have successfully demonstrated the production of vascular EC under GMP-compliant conditions suitable for clinical evaluation.

  12. Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis

    NASA Astrophysics Data System (ADS)

    Čupić, Željko; Marković, Vladimir M.; Maćešić, Stevan; Stanojević, Ana; Damjanović, Svetozar; Vukojević, Vladana; Kolar-Anić, Ljiljana

    2016-03-01

    Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamic-pituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations.

  13. Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis.

    PubMed

    Weaver, Lehn K; Behrens, Edward M

    2017-03-01

    Cytokine storm syndromes require rapid diagnosis and treatment to limit the morbidity and mortality caused by the hyperinflammatory state that characterizes these devastating conditions. Herein, we discuss the current knowledge that guides our therapeutic decision-making and personalization of treatment for patients with cytokine storm syndromes. Firstly, ICU-level supportive care is often required to stabilize patients with fulminant disease while additional diagnostic evaluations proceed to determine the underlying cause of cytokine storm. Pharmacologic interventions should be focused on removing the inciting trigger of inflammation and initiation of an individualized immunosuppressive regimen when immune activation is central to the underlying disease pathophysiology. Monitoring for a clinical response is required to ensure that changes in the therapeutic regimen can be made as clinically warranted. Escalation of immunosuppression may be required if patients respond poorly to the initial therapeutic interventions, while a slow wean of immunosuppression in patients who improve can limit medication-related toxicities. In certain scenarios, a decision must be made whether an individual patient requires hematopoietic cell transplantation to prevent recurrence of disease. Despite these interventions, significant morbidity and mortality remains for cytokine storm patients. Therefore, we use this review to propose a clinical schema to guide current and future attempts to design rational therapeutic interventions for patients suffering from these devastating conditions, which we believe speeds the diagnosis of disease, limits medication-related toxicities, and improves clinical outcomes by targeting the heterogeneous and dynamic mechanisms driving disease in each individual patient.

  14. 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.

  15. Changes of intranetwork and internetwork functional connectivity in Alzheimer’s disease and mild cognitive impairment

    NASA Astrophysics Data System (ADS)

    Zhu, Haoze; Zhou, Peng; Alcauter, Sarael; Chen, Yuanyuan; Cao, Hongbao; Tian, Miao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Zhao, Xin; He, Feng; Ni, Hongyan; Gao, Wei

    2016-08-01

    Objective. Alzheimer’s disease (AD) is a serious neurodegenerative disorder characterized by deficits of working memory, attention, language and many other cognitive functions. Although different stages of the disease are relatively well characterized by clinical criteria, stage-specific pathological changes in the brain remain relatively poorly understood, especially at the level of large-scale functional networks. In this study, we aimed to characterize the potential disruptions of large-scale functional brain networks based on a sample including amnestic mild cognition impairment (aMCI) and AD patients to help delineate the underlying stage-dependent AD pathology. Approach. We sought to identify the neural connectivity mechanisms of aMCI and AD through examination of both intranetwork and internetwork interactions among four of the brain’s key networks, namely dorsal attention network (DAN), default mode network (DMN), executive control network (ECN) and salience network (SAL). We analyzed functional connectivity based on resting-state functional magnetic resonance imaging (rs-fMRI) data from 25 Alzheimer’s disease patients, 20 aMCI patients and 35 elderly normal controls (NC). Main results. Intranetwork functional disruptions within the DAN and ECN were detected in both aMCI and AD patients. Disrupted intranetwork connectivity of DMN and anti-correlation between DAN and DMN were observed in AD patients. Moreover, aMCI-specific alterations in the internetwork functional connectivity of SAL were observed. Significance. Our results confirmed previous findings that AD pathology was related to dysconnectivity both within and between resting-state networks but revealed more spatial details. Moreover, the SAL network, reportedly flexibly coupling either with the DAN or DMN networks during different brain states, demonstrated interesting alterations specifically in the early stage of the disease.

  16. Incidence of cassava mosaic disease and associated whitefly vectors in South West and North Central Nigeria: Data exploration.

    PubMed

    Eni, Angela O; Efekemo, Oghenevwairhe P; Soluade, Mojisola G; Popoola, Segun I; Atayero, Aderemi A

    2018-08-01

    Cassava mosaic disease (CMD) is one of the most economically important viral diseases of cassava, an important staple food for over 800 million people in the tropics. Although several Cassava mosaic virus species associated with CMD have been isolated and characterized over the years, several new super virulent strains of these viruses have evolved due to genetic recombination between diverse species. In this data article, field survey data collected from 184 cassava farms in 12 South Western and North Central States of Nigeria in 2015 are presented and extensively explored. In each State, one cassava farm was randomly selected as the first farm and subsequent farms were selected at 10 km intervals, except in locations were cassava farms are sporadically located. In each selected farm, 30 cassava plants were sampled along two diagonals and all selected plant was scored for the presence or absence of CMD symptoms. Cassava mosaic disease incidence and associated whitefly vectors in South West and North Central Nigeria are explored using relevant descriptive statistics, box plots, bar charts, line graphs, and pie charts. In addition, correlation analysis, Analysis of Variance (ANOVA), and multiple comparison post-hoc tests are performed to understand the relationship between the numbers of whiteflies counted, uninfected farms, infected farms, and the mean of symptom severity in and across the States under investigation. The data exploration provided in this data article is considered adequate for objective assessment of the incidence and symptom severity of cassava mosaic disease and associated whitefly vectors in farmers' fields in these parts of Nigeria where cassava is heavily cultivated.

  17. Disease Risk in a Dynamic Environment: The Spread of Tick-Borne Pathogens in Minnesota, USA

    PubMed Central

    Robinson, Stacie J.; Neitzel, David F.; Moen, Ronald A.; Craft, Meggan E.; Hamilton, Karin E.; Johnson, Lucinda B.; Mulla, David J.; Munderloh, Ulrike G.; Redig, Patrick T.; Smith, Kirk E.; Turner, Clarence L.; Umber, Jamie K.; Pelican, Katharine M.

    2015-01-01

    As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease. PMID:25281302

  18. Disease risk in a dynamic environment: the spread of tick-borne pathogens in Minnesota, USA.

    PubMed

    Robinson, Stacie J; Neitzel, David F; Moen, Ronald A; Craft, Meggan E; Hamilton, Karin E; Johnson, Lucinda B; Mulla, David J; Munderloh, Ulrike G; Redig, Patrick T; Smith, Kirk E; Turner, Clarence L; Umber, Jamie K; Pelican, Katharine M

    2015-03-01

    As humans and climate change alter the landscape, novel disease risk scenarios emerge. Understanding the complexities of pathogen emergence and subsequent spread as shaped by landscape heterogeneity is crucial to understanding disease emergence, pinpointing high-risk areas, and mitigating emerging disease threats in a dynamic environment. Tick-borne diseases present an important public health concern and incidence of many of these diseases are increasing in the United States. The complex epidemiology of tick-borne diseases includes strong ties with environmental factors that influence host availability, vector abundance, and pathogen transmission. Here, we used 16 years of case data from the Minnesota Department of Health to report spatial and temporal trends in Lyme disease (LD), human anaplasmosis, and babesiosis. We then used a spatial regression framework to evaluate the impact of landscape and climate factors on the spread of LD. Finally, we use the fitted model, and landscape and climate datasets projected under varying climate change scenarios, to predict future changes in tick-borne pathogen risk. Both forested habitat and temperature were important drivers of LD spread in Minnesota. Dramatic changes in future temperature regimes and forest communities predict rising risk of tick-borne disease.

  19. Evaluating the utility of companion animal tick surveillance practices for monitoring spread and occurrence of human Lyme disease in West Virginia, 2014-2016.

    PubMed

    Hendricks, Brian; Mark-Carew, Miguella; Conley, Jamison

    2017-11-13

    Domestic dogs and cats are potentially effective sentinel populations for monitoring occurrence and spread of Lyme disease. Few studies have evaluated the public health utility of sentinel programmes using geo-analytic approaches. Confirmed Lyme disease cases diagnosed by physicians and ticks submitted by veterinarians to the West Virginia State Health Department were obtained for 2014-2016. Ticks were identified to species, and only Ixodes scapularis were incorporated in the analysis. Separate ordinary least squares (OLS) and spatial lag regression models were conducted to estimate the association between average numbers of Ix. scapularis collected on pets and human Lyme disease incidence. Regression residuals were visualised using Local Moran's I as a diagnostic tool to identify spatial dependence. Statistically significant associations were identified between average numbers of Ix. scapularis collected from dogs and human Lyme disease in the OLS (β=20.7, P<0.001) and spatial lag (β=12.0, P=0.002) regression. No significant associations were identified for cats in either regression model. Statistically significant (P≤0.05) spatial dependence was identified in all regression models. Local Moran's I maps produced for spatial lag regression residuals indicated a decrease in model over- and under-estimation, but identified a higher number of statistically significant outliers than OLS regression. Results support previous conclusions that dogs are effective sentinel populations for monitoring risk of human exposure to Lyme disease. Findings reinforce the utility of spatial analysis of surveillance data, and highlight West Virginia's unique position within the eastern United States in regards to Lyme disease occurrence.

  20. Drinking despite health problems among individuals with liver disease across the United States.

    PubMed

    Elliott, Jennifer C; Stohl, Malka; Hasin, Deborah S

    2017-07-01

    Heavy drinking is harmful for individuals with liver disease. However, some of these individuals drink despite knowledge of the risks. The current study aims to identify factors underlying drinking despite health problems among individuals with liver disease. The current study utilizes a subsample of individuals reporting past-year liver disease and at least one drink in the past year (n=331), taken from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III), a large nationally representative survey of the United States. Participants reported on drinking despite health problems, symptoms of psychopathology, and family history of alcohol problems in a cross-sectional survey. Drug use disorders (Adjusted Odds Ratio [AOR]=2.68), as well as borderline, antisocial, and schizotypal personality disorders (AORs=2.50-4.10), were associated with increased likelihood of drinking despite health problems among individuals with liver disease, all ps<0.05. Any anxiety disorder trended toward significance (AOR=2.22), p=0.06, but major depressive disorder was not associated with increased risk, (AOR=0.99), ps=0.97. Individuals with a family history of alcohol problems were also more likely to drink despite health problems (AOR=2.79), p<0.05. Several types of psychopathology, as well as a family history of alcohol problems, increased the likelihood of drinking despite health problems among individuals with liver disease. These findings highlight the need to intervene with heavily drinking individuals with liver disease, who may be drinking due to familial risk and/or comorbid psychopathology. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Effect of kshara basti and nirgundi ghana vati on amavata (rheumatoid arthritis).

    PubMed

    Thanki, Krishna; Bhatt, Nilesh; Shukla, V D

    2012-01-01

    Ayurveda has taken the foremost place in the management of crippling disease, one of them is Amavata which can be compared with Rheumatoid Arthritis due to its clinical appearance. Due to wide spectrum of disease, much prevalence in the society and lack of effective medicament, the disease is being chosen for the study. The line of treatment described for the disease in Chakradatta can be summarized under following captions. i.e to bring Agni to normal state to digest Ama, and eliminate vitiated Vata and Ama. Thus, here Kshara Basti is selected for the present study as Samshodhana process which corrects all of above captions. It is mentioned in Chikitsa Sutra described by Chakradatta. Nirgundi has Amavatahara property which is stated by Bhavaprakasha, considering which Nirgundi Patra Ghanavati is selected as Shamana drug. Total 50 randomly selected patients of Amavata were registered among them 45 were completed the treatment. Kshara Basti in the format of Kala Basti was given to these patients and Nirgundi Ghana Vati was given for one month. Statistically significant improvement was found in ESR, RA factor (quantitative) and also highly significant results were found in symptoms of Amavata. Moderate improvement was seen in 40% of patients, 35.56% patients got marked improvement, while mild improvement was found in 24.44% of patients.

  2. Effect of Kshara Basti and Nirgundi Ghana Vati on Amavata (Rheumatoid Arthritis)

    PubMed Central

    Thanki, Krishna; Bhatt, Nilesh; Shukla, V. D.

    2012-01-01

    Ayurveda has taken the foremost place in the management of crippling disease, one of them is Amavata which can be compared with Rheumatoid Arthritis due to its clinical appearance. Due to wide spectrum of disease, much prevalence in the society and lack of effective medicament, the disease is being chosen for the study. The line of treatment described for the disease in Chakradatta can be summarized under following captions. i.e to bring Agni to normal state to digest Ama, and eliminate vitiated Vata and Ama. Thus, here Kshara Basti is selected for the present study as Samshodhana process which corrects all of above captions. It is mentioned in Chikitsa Sutra described by Chakradatta. Nirgundi has Amavatahara property which is stated by Bhavaprakasha, considering which Nirgundi Patra Ghanavati is selected as Shamana drug. Total 50 randomly selected patients of Amavata were registered among them 45 were completed the treatment. Kshara Basti in the format of Kala Basti was given to these patients and Nirgundi Ghana Vati was given for one month. Statistically significant improvement was found in ESR, RA factor (quantitative) and also highly significant results were found in symptoms of Amavata. Moderate improvement was seen in 40% of patients, 35.56% patients got marked improvement, while mild improvement was found in 24.44% of patients. PMID:23049184

  3. The lyme disease pathogen has no effect on the survival of its rodent reservoir host.

    PubMed

    Voordouw, Maarten J; Lachish, Shelly; Dolan, Marc C

    2015-01-01

    Zoonotic pathogens that cause devastating morbidity and mortality in humans may be relatively harmless in their natural reservoir hosts. The tick-borne bacterium Borrelia burgdorferi causes Lyme disease in humans but few studies have investigated whether this pathogen reduces the fitness of its reservoir hosts under natural conditions. We analyzed four years of capture-mark-recapture (CMR) data on a population of white-footed mice, Peromyscus leucopus, to test whether B. burgdorferi and its tick vector affect the survival of this important reservoir host. We used a multi-state CMR approach to model mouse survival and mouse infection rates as a function of a variety of ecologically relevant explanatory factors. We found no effect of B. burgdorferi infection or tick burden on the survival of P. leucopus. Our estimates of the probability of infection varied by an order of magnitude (0.051 to 0.535) and were consistent with our understanding of Lyme disease in the Northeastern United States. B. burgdorferi establishes a chronic avirulent infection in their rodent reservoir hosts because this pathogen depends on rodent mobility to achieve transmission to its sedentary tick vector. The estimates of B. burgdorferi infection risk will facilitate future theoretical studies on the epidemiology of Lyme disease.

  4. Burden of Outdoor Air Pollution in Kerala, India—A First Health Risk Assessment at State Level.

    PubMed

    Tobollik, Myriam; Razum, Oliver; Wintermeyer, Dirk; Plass, Dietrich

    2015-08-28

    Ambient air pollution causes a considerable disease burden, particularly in South Asia. The objective of the study is to test the feasibility of applying the environmental burden of disease method at state level in India and to quantify a first set of disease burden estimates due to ambient air pollution in Kerala. Particulate Matter (PM) was used as an indicator for ambient air pollution. The disease burden was quantified in Years of Life Lost (YLL) for the population (30 + years) living in urban areas of Kerala. Scenario analyses were performed to account for uncertainties in the input parameters. 6108 (confidence interval (95% CI): 4150-7791) of 81,636 total natural deaths can be attributed to PM, resulting in 96,359 (95% CI: 65,479-122,917) YLLs due to premature mortality (base case scenario, average for 2008-2011). Depending on the underlying assumptions the results vary between 69,582 and 377,195 YLLs. Around half of the total burden is related to cardiovascular deaths. Scenario analyses show that a decrease of 10% in PM concentrations would save 15,904 (95% CI: 11,090-19,806) life years. The results can be used to raise awareness about air quality standards at a local level and to support decision-making processes aiming at cleaner and healthier environments.

  5. Cancer epidemiology in the freely associated U.S. Pacific Island jurisdictions: challenges and methodologic issues.

    PubMed

    Katz, Alan R; Palafox, Neal A; Johnson, David B; Yamada, Seiji; Ou, Alan C; Minami, Jill S

    2004-09-01

    The health care systems of the U.S.-associated Pacific Island jurisdictions, especially the three freely associated states (Federated States of Micronesia, Republic of the Marshall Islands, and Republic of Belau), are faced with problems similar to developing countries such as malnutrition and infectious diseases, as well as diseases relating to westernization such as diabetes, heart disease, and cancer. Although cancer has emerged as an important cause of morbidity and mortality in the Pacific, little population-based data are currently available. This paper addresses some of the practical and methodological challenges to obtaining accurate and reliable cancer data in these jurisdictions. This paper discusses the use of annualized period prevalence to allow for some measurement of cancer burden when cancer incidence cannot be accurately calculated. This method, however, has its own limitations as cancer prevalence relates to both incidence and duration of illness, and numerous factors impact survival potential (i.e., preexisting diseases, lifestyle practices, and access to treatment). In addition, under-ascertainment and data quality issues will impact any cancer morbidity or mortality measurements. Thus, improvement in the health care systems, including the creation and ongoing support of active cancer registries would be the optimal approach to better delineating cancer occurrence and risk for the populations of these Pacific Island jurisdictions.

  6. Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation.

    PubMed

    Da Cunha, Claudio; Boschen, Suelen L; Gómez-A, Alexander; Ross, Erika K; Gibson, William S J; Min, Hoon-Ki; Lee, Kendall H; Blaha, Charles D

    2015-11-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Beneficial and detrimental role of adenosine signaling in diseases and therapy

    PubMed Central

    Liu, Hong

    2015-01-01

    Adenosine is a major signaling nucleoside that orchestrates cellular and tissue adaptation under energy depletion and ischemic/hypoxic conditions by activation of four G protein-coupled receptors (GPCR). The regulation and generation of extracellular adenosine in response to stress are critical in tissue protection. Both mouse and human studies reported that extracellular adenosine signaling plays a beneficial role during acute states. However, prolonged excess extracellular adenosine is detrimental and contributes to the development and progression of various chronic diseases. In recent years, substantial progress has been made to understand the role of adenosine signaling in different conditions and to clarify its significance during the course of disease progression in various organs. These efforts have and will identify potential therapeutic possibilities for protection of tissue injury at acute stage by upregulation of adenosine signaling or attenuation of chronic disease progression by downregulation of adenosine signaling. This review is to summarize current progress and the importance of adenosine signaling in different disease stages and its potential therapeutic effects. PMID:26316513

  8. Toward sophisiticated basal ganglia neuromodulation: review on basal gaglia deep brain stimulation

    PubMed Central

    Da Cunha, Claudio; Boschen, Suelen L.; Gómez-A, Alexander; Ross, Erika K.; Gibson, William S. J.; Min, Hoon-Ki; Lee, Kendall H.; Blaha, Charles D.

    2015-01-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727

  9. Acute coronary syndromes in patients with renal failure.

    PubMed

    McCullough, Peter A

    2003-07-01

    As the rates of obesity and diabetes continue to rise sharply in the United States, there is a secondary epidemic of diabetic nephropathy, chronic kidney disease, and end-stage renal disease requiring renal replacement therapy. Cardiovascular disease is the leading cause of death in patients with renal disease. Many sources of information support the concept that the metabolic condition caused by renal failure is an independent cardiac risk factor with a direct relationship to the pathogenesis of atherosclerosis, acute coronary syndromes (ACS), heart failure, and arrhythmias. An estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) has consistently been shown to be the most powerful predictor of adverse outcomes in ACS. This paper focuses on ACS and highlights the major issues with respect to diagnosis and treatment in patients with underlying renal failure. Because patients with renal disease are routinely excluded from clinical trials of ACS, we draw upon a variety of clinical data sets to gather an evidenced-based approach to this important and growing population of patients.

  10. Hormonal control of angiotensinogen production.

    PubMed

    Dzau, V J; Herrmann, H C

    The renin-angiotensin-aldosterone system appears to be under neural and hormonal control. Plasma angiotensinogen concentration is elevated in Cushing's disease, during pregnancy and in women taking oral contraceptives. An in vitro liver slice system was used to study the hormonal control of angiotensinogen synthesis and release in the rat. Dexamethasone administration in vivo resulted in increase in the in vitro rate of release of angiotensinogen by liver slices into the incubation media. This increase was inhibited by actinomycin D, an inhibitor of protein synthesis and vincristine which blocks secretion. Similarly, ethinyl estradiol treatment resulted in a 50% increase in angiotensinogen production. Hyperthyroid state was achieved by injecting rats with L-thyroxine daily for seven days. Hepatic production rate of angiotensinogen rose 21/2-fold above control and was accompanied by increases in plasma angiotensinogen concentration and plasma renin activity. In contrast, plasma angiotensinogen concentration and plasma renin activity were reduced in thyroidectomized rats. The rate of angiotensinogen production by liver slices of these rats decreased by five-fold below that of intact animals. These changes were largely corrected when thyroidectomized rats were treated with replacement doses of L-thyroxine. We conclude that hepatic angiotensinogen biosynthesis is under hormonal control. Glucocorticoid, estrogen and thyroid hormones all stimulate angiotensinogen production. These results may in part explain the pathogenesis of hypertension associated with certain disease states.

  11. Apathy and noradrenaline: silent partners to mild cognitive impairment in Parkinson's disease?

    PubMed

    Loued-Khenissi, Leyla; Preuschoff, Kerstin

    2015-08-01

    Mild cognitive impairment (MCI) is a comorbid factor in Parkinson's disease. The aim of this review is to examine the recent neuroimaging findings in the search for Parkinson's disease MCI (PD-MCI) biomarkers to gain insight on whether MCI and specific cognitive deficits in Parkinson's disease implicate striatal dopamine or another system. The evidence implicates a diffuse pathophysiology in PD-MCI rather than acute dopaminergic involvement. On the one hand, performance in specific cognitive domains, notably in set-shifting and learning, appears to vary with dopaminergic status. On the other hand, motivational states in Parkinson's disease along with their behavioral and physiological indices suggest a noradrenergic contribution to cognitive deficits in Parkinson's disease. Finally, Parkinson's disease's pattern of neurodegeneration offers an avenue for continued research in nigrostriatal dopamine's role in distinct behaviors, as well as the specification of dorsal and ventral striatal functions. The search for PD-MCI biomarkers has employed an array of neuroimaging techniques, but still yields divergent findings. This may be due in part to MCI's broad definition, encompassing heterogeneous cognitive domains, only some of which are affected in Parkinson's disease. Most domains falling under the MCI umbrella include fronto-dependent executive functions, whereas others, notably learning, rely on the basal ganglia. Given the deterioration of the nigrostriatal dopaminergic system in Parkinson's disease, it has been the prime target of PD-MCI investigation. By testing well defined cognitive deficits in Parkinson's disease, distinct functions can be attributed to specific neural systems, overcoming conflicting results on PD-MCI. Apart from dopamine, other systems such as the neurovascular or noradrenergic systems are affected in Parkinson's disease. These factors may be at the basis of specific facets of PD-MCI for which dopaminergic involvement has not been conclusive. Finally, the impact of both dopaminergic and noradrenergic deficiency on motivational states in Parkinson's disease is examined in light of a plausible link between apathy and cognitive deficits.

  12. Validity of the rheumatoid arthritis impact of disease (RAID) score and definition of cut-off points for disease activity states in a population-based European cohort of patients with rheumatoid arthritis.

    PubMed

    Salaffi, Fausto; Di Carlo, Marco; Vojinovic, Jelena; Tincani, Angela; Sulli, Alberto; Soldano, Stefano; Andreoli, Laura; Dall'Ara, Francesca; Ionescu, Ruxandra; Simić Pašalić, Katarina; Balčune, Ineta; Ferraz-Amaro, Iván; Tlustochowicz, Malgorzata; Butrimienė, Irena; Punceviciene, Egle; Toroptsova, Natalia; Grazio, Simeon; Morović-Vergles, Jadranka; Masaryk, Pavol; Otsa, Kati; Bernardes, Miguel; Boyadzhieva, Vladimira; Cutolo, Maurizio

    2018-05-01

    To assess the validity of the rheumatoid arthritis impact of disease (RAID) for measuring disease activity of rheumatoid arthritis (RA) and to determine cut-off values for defining the disease activity states. A total of 622 RA patients from an European database have been included. Cross-validation was based on assessment of convergent and discriminant validity. Optimal cut-offs were determined against external criteria by calculating the respective 25th and 75th percentiles mean values of RAID. External criteria included definitions for remission (REM), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA), cut-offs of the 28-joint disease activity score-C-reactive protein (DAS28-CRP) score. The RAID showed a moderate degree of correlation with respect to DAS28-CRP (rho=0.417; P<0.0001). The receiver operating characteristic (ROC) curves to discriminate the ability of RAID to distinguish patients with active and non-active disease was very good with an area under the curve (AUC) of 0.847 (95% confidence interval [CI]: 0.816 to 0.878; P<0.0001). Based on the distributions of RAID in the different disease activity groups, we propose the following cut-off values for REM: RAID ≤3; for LDA: RAID >3 and ≤4; for MDA: RAID >4 and ≤6; for HDA: RAID >6. Mean RAID differed significantly between patients classified as REM, LDA, MDA or HDA (P=0.001). The cut-offs revealed good measurement characteristics in cross-validation analysis, had great discriminatory performance in distinguishing patients with different levels of disease activity and are suited for widespread use in everyday practice application and research. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  13. Advances in Meningeal Immunity.

    PubMed

    Rua, Rejane; McGavern, Dorian B

    2018-06-01

    The central nervous system (CNS) is an immunologically specialized tissue protected by a blood-brain barrier. The CNS parenchyma is enveloped by a series of overlapping membranes that are collectively referred to as the meninges. The meninges provide an additional CNS barrier, harbor a diverse array of resident immune cells, and serve as a crucial interface with the periphery. Recent studies have significantly advanced our understanding of meningeal immunity, demonstrating how a complex immune landscape influences CNS functions under steady-state and inflammatory conditions. The location and activation state of meningeal immune cells can profoundly influence CNS homeostasis and contribute to neurological disorders, but these cells are also well equipped to protect the CNS from pathogens. In this review, we discuss advances in our understanding of the meningeal immune repertoire and provide insights into how this CNS barrier operates immunologically under conditions ranging from neurocognition to inflammatory diseases. Published by Elsevier Ltd.

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

    Smith, S; Danganan, L; Tammero, L

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed advanced rapid diagnostics that may be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the potential to improve our nation's ability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect animal populations of high economic importance in themore » United States. Under 2005 DHS funding we have developed multiplexed (MUX) nucleic-acid-based PCR assays that combine foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease (SVD) and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1 or Infectious Bovine Rhinotracheitus IBR), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus BPSV, Orf of sheep, and Pseudocowpox). Under 2006 funding we have developed a Multiplexed PCR [MUX] porcine assay for detection of FMDV with rule out tests for VESV and SVD foreign animal diseases in addition to one other domestic vesicular animal disease vesicular stomatitis virus (VSV) and one domestic animal disease of swine porcine reproductive and respiratory syndrome (PRRS). We have also developed a MUX bovine assay for detection of FMDV with rule out tests for the two bovine foreign animal diseases malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses which are of two bovine types bovine papular stomatitis virus (BPSV) and psuedocowpox (PCP). This document provides details of signature generation, evaluation, and testing, as well as the specific methods and materials used. A condensed summary of the development, testing and performance of the multiplexed assay panel was presented in a 126 page separate document, entitled 'Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out'. This supplemental document provides additional details of large amount of data collected for signature generation, evaluation, and testing, as well as the specific methods and materials used for all steps in the assay development and utilization processes. In contrast to last years effort, the development of the bovine and porcine panels is pending additional work to complete analytical characterization of FMDV, VESV, VSV, SVD, RPV and MCF. The signature screening process and final panel composition impacts this effort. The unique challenge presented this year was having strict predecessor limitations in completing characterization, where efforts at LLNL must preceed efforts at PIADC, such challenges were alleviated in the 2006 reporting by having characterization data from the interlaboratory comparison and at Plum Island under AgDDAP project. We will present an addendum at a later date with additional data on the characterization of the porcine and bovine multiplex assays when that data is available.« less

  15. Precipitation and the occurrence of lyme disease in the Northeastern United States

    USGS Publications Warehouse

    McCabe, G.J.; Bunnell, J.E.

    2004-01-01

    The occurrence of Lyme disease is a growing concern in the United States, and various studies have been performed to understand the factors related to Lyme disease occurrence. In the United States, Lyme disease has occurred most frequently in the northeastern United States. Positive correlations between the number of cases of Lyme disease reported in the northeastern United States during the 1992-2002 period indicate that late spring/early summer precipitation was a significant climate factor affecting the occurrence of Lyme disease. When late spring/early summer precipitation was greater than average, the occurrence of Lyme disease was above average, possibly due to increased tick activity and survival rate during wet conditions. Temperature did not seem to explain the variability in Lyme disease reports for the northeastern United States. ?? Mary Ann Liebert, Inc.

  16. When structure affects function--the need for partial volume effect correction in functional and resting state magnetic resonance imaging studies.

    PubMed

    Dukart, Juergen; Bertolino, Alessandro

    2014-01-01

    Both functional and also more recently resting state magnetic resonance imaging have become established tools to investigate functional brain networks. Most studies use these tools to compare different populations without controlling for potential differences in underlying brain structure which might affect the functional measurements of interest. Here, we adapt a simulation approach combined with evaluation of real resting state magnetic resonance imaging data to investigate the potential impact of partial volume effects on established functional and resting state magnetic resonance imaging analyses. We demonstrate that differences in the underlying structure lead to a significant increase in detected functional differences in both types of analyses. Largest increases in functional differences are observed for highest signal-to-noise ratios and when signal with the lowest amount of partial volume effects is compared to any other partial volume effect constellation. In real data, structural information explains about 25% of within-subject variance observed in degree centrality--an established resting state connectivity measurement. Controlling this measurement for structural information can substantially alter correlational maps obtained in group analyses. Our results question current approaches of evaluating these measurements in diseased population with known structural changes without controlling for potential differences in these measurements.

  17. Autocrine release of angiopoietin-2 mediates cerebrovascular disintegration in Moyamoya disease

    PubMed Central

    Blecharz, Kinga G; Frey, Dietmar; Schenkel, Tobias; Prinz, Vincent; Bedini, Gloria; Krug, Susanne M; Czabanka, Marcus; Wagner, Josephin; Fromm, Michael; Bersano, Anna

    2016-01-01

    Moyamoya disease is a rare steno-occlusive cerebrovascular disorder often resulting in hemorrhagic and ischemic strokes. Although sharing the same ischemic stimulus with atherosclerotic cerebrovascular disease, Moyamoya disease is characterized by a highly instable cerebrovascular system which is prone to rupture due to pathological neovascularization. To understand the molecular mechanisms underlying this instability, angiopoietin-2 gene expression was analyzed in middle cerebral artery lesions obtained from Moyamoya disease and atherosclerotic cerebrovascular disease patients. Angiopoietin-2 was significantly up-regulated in Moyamoya vessels, while serum concentrations of soluble angiopoietins were not changed. For further evaluations, cerebral endothelial cells incubated with serum from these patients in vitro were applied. In contrast to atherosclerotic cerebrovascular disease serum, Moyamoya disease serum induced an angiopoietin-2 overexpression and secretion, accompanied by loss of endothelial integrity. These effects were absent or inverse in endothelial cells of non-brain origin suggesting brain endothelium specificity. The destabilizing effects on brain endothelial cells to Moyamoya disease serum were partially suppressed by the inhibition of angiopoietin-2. Our findings define brain endothelial cells as the potential source of vessel-destabilizing factors inducing the high plasticity state and disintegration in Moyamoya disease in an autocrine manner. We also provide new insights into Moyamoya disease pathophysiology that may be helpful for preventive treatment strategies in future. PMID:27381827

  18. Morgellons disease: Analysis of a population with clinically confirmed microscopic subcutaneous fibers of unknown etiology.

    PubMed

    Savely, Virginia R; Stricker, Raphael B

    2010-05-13

    Morgellons disease is a controversial illness in which patients complain of stinging, burning, and biting sensations under the skin. Unusual subcutaneous fibers are the unique objective finding. The etiology of Morgellons disease is unknown, and diagnostic criteria have yet to be established. Our goal was to identify prevalent symptoms in patients with clinically confirmed subcutaneous fibers in order to develop a case definition for Morgellons disease. Patients with subcutaneous fibers observed on physical examination (designated as the fiber group) were evaluated using a data extraction tool that measured clinical and demographic characteristics. The prevalence of symptoms common to the fiber group was then compared with the prevalence of these symptoms in patients with Lyme disease and no complaints of skin fibers. The fiber group consisted of 122 patients. Significant findings in this group were an association with tick-borne diseases and hypothyroidism, high numbers from two states (Texas and California), high prevalence in middle-aged Caucasian women, and an increased prevalence of smoking and substance abuse. Although depression was noted in 29% of the fiber patients, pre-existing delusional disease was not reported. After adjusting for nonspecific symptoms, the most common symptoms reported in the fiber group were: crawling sensations under the skin; spontaneously appearing, slow-healing lesions; hyperpigmented scars when lesions heal; intense pruritus; seed-like objects, black specks, or "fuzz balls" in lesions or on intact skin; fine, thread-like fibers of varying colors in lesions and intact skin; lesions containing thick, tough, translucent fibers that are highly resistant to extraction; and a sensation of something trying to penetrate the skin from the inside out. This study of the largest clinical cohort reported to date provides the basis for an accurate and clinically useful case definition for Morgellons disease.

  19. Epidemiology of Infectious Disease–Related Death After Release from Prison, Washington State, United States, and Queensland, Australia: A Cohort Study

    PubMed Central

    Blatchford, Patrick J.; Forsyth, Simon J.; Stern, Marc F.; Kinner, Stuart A.

    2016-01-01

    Objectives People in prison may be at high risk for infectious diseases and have an elevated risk of death immediately after release compared with later; their risk of death is elevated for at least a decade after release. We compared rates, characteristics, and prison-related risk factors for infectious disease–related mortality among people released from prisons in Queensland, Australia, and Washington State, United States, regions with analogous available data. Methods We analyzed data from retrospective cohort studies of people released from prison in Queensland (1997–2007, n=37,180) and Washington State (1999–2009, n=76,208) and linked identifiers from each cohort to its respective national death index. We estimated infectious disease–related mortality rates (deaths per person-years in community) and examined associations using Cox proportional hazard models. Results The most frequent infectious disease–related underlying cause of death after release from prison was pneumonia (43%, 23/54 deaths) in the Australian cohort and viral hepatitis (40%, 69/171 deaths) in the U.S. cohort. The infectious disease–related mortality rate was significantly higher in the U.S. cohort than in the Australian cohort (51.2 vs. 26.5 deaths per 100,000 person-years; incidence rate ratio = 1.93, 95% confidence interval 1.42, 2.62). In both cohorts, increasing age was strongly associated with mortality from infectious diseases. Conclusion Differences in the epidemiology of infectious disease–related mortality among people released from prison may reflect differences in patterns of community health service delivery in each region. These findings highlight the importance of preventing and treating hepatitis C and other infectious diseases during the transition from prison to the community. PMID:27453602

  20. Elimination of Neglected Diseases in Latin America and the Caribbean: A Mapping of Selected Diseases

    PubMed Central

    Schneider, Maria Cristina; Aguilera, Ximena Paz; Barbosa da Silva Junior, Jarbas; Ault, Steven Kenyon; Najera, Patricia; Martinez, Julio; Requejo, Raquel; Nicholls, Ruben Santiago; Yadon, Zaida; Silva, Juan Carlos; Leanes, Luis Fernando; Periago, Mirta Roses

    2011-01-01

    In Latin America and the Caribbean, around 195 million people live in poverty, a situation that increases the burden of some infectious diseases. Neglected diseases, in particular, are often restricted to poor, marginalized sections of the population. Tools exist to combat these diseases, making it imperative to work towards their elimination. In 2009, the Pan American Health Organization (PAHO) received a mandate to support the countries in the Region in eliminating neglected diseases and other poverty-related infections. The objective of this study is to analyze the presence of selected diseases using geo-processing techniques. Five diseases with information available at the first sub-national level (states) were mapped, showing the presence of the disease (“hotspots”) and overlap of diseases (“major hotspots”). In the 45 countries/territories (approximately 570 states) of the Region, there is: lymphatic filariasis in four countries (29 states), onchocerciasis in six countries (25 states), schistosomiasis in four countries (39 states), trachoma in three countries (29 states), and human rabies transmitted by dogs in ten countries (20 states). Of the 108 states with one or more of the selected diseases, 36 states present the diseases in overlapping areas (“major hotspots”). Additional information about soil-transmitted helminths was included. The analysis suggests a majority of the selected diseases are not widespread and can be considered part of an unfinished agenda with elimination as a goal. Integrated plans and a comprehensive approach, ensuring access to existing diagnostic and treatment methods, and establishing a multi-sectoral agenda that addresses social determinants, including access to adequate water and sanitation, are required. Future studies can include additional diseases, socio-economic and environmental variables. PMID:21358810

  1. [Advances in the knowledge of the use of micronutrients in artificial nutrition].

    PubMed

    Muñoz García, M; Pérez Menéndez-Conde, C; Bermejo Vicedo, T

    2011-01-01

    Micronutrients are defined as those compounds necessary for the adequate physiological status of the organism and that may be administered through the daily diet either enteral or parenteral. The term micronutrient encompasses the vitamins and oligoelements, also termed trace elements. Vitamins cannot be synthesized by the organism and are categorized in two groups: water-soluble vitamins (the vitamin B group, C, folic acid, and biotin) and lipid-soluble vitamins (A, D, E, and K). Oligoelements are found in small amounts in the human body, and copper, cobalt, chrome, iron, iodine, manganese, molybdenum, nickel, selenium, and zinc are considered to be essential. The important role of micronutrients in critically-ill patients has been demonstrated, and their influence on the immune system, cancer, burnt, septic, and poly-traumatized patients has extensively been put in evidence. It is important to establish the micronutrients demands for each individual in order to achieve an adequate intake. However, there is little evidence on the necessary intake to achieve proper physiological functioning under different pathologies; therefore, studies bringing light to this situation are needed. The aim of this review is to update the current state of knowledge on micronutrients supplementation in the adult population with pathologies such as cancer, coronary and cardiovascular disease, bowel inflammatory disease, short-bowel syndrome, cystic fibrosis, liver disease, renal failure, respiratory failure, the surgical patient, big-burnt patient, pancreatitis, poly-traumatized patients, sepsis and HIV. After the bibliographical search, we describe the current state of knowledge regarding micronutrients intake in artificial nutrition under the above-mentioned pathologies.

  2. Epigenetic Principles and Mechanisms Underlying Nervous System Functions in Health and Disease

    PubMed Central

    Mehler, Mark F.

    2009-01-01

    Epigenetics and epigenomic medicine encompass a new science of brain and behavior that are already providing unique insights into the mechanisms underlying brain development, evolution, neuronal and network plasticity and homeostasis, senescence, the etiology of diverse neurological diseases and neural regenerative processes. Epigenetic mechanisms include DNA methylation, histone modifications, nucleosome repositioning, higher-order chromatin remodeling, non-coding RNAs, and RNA and DNA editing. RNA is centrally involved in directing these processes, implying that the transcriptional state of the cell is the primary determinant of epigenetic memory. This transcriptional state can be modified by internal and external cues affecting gene expression and post-transcriptional processing, but also by RNA and DNA editing through activity-dependent intracellular transport and modulation of RNAs and RNA regulatory supercomplexes, and through trans-neuronal and systemic trafficking of functional RNA subclasses. These integrated processes promote dynamic reorganization of nuclear architecture and the genomic landscape to modulate functional gene and neural networks with complex temporal and spatial trajectories. Epigenetics represents the long sought after molecular interface mediating gene-environmental interactions during critical periods throughout the lifecycle. The discipline of environmental epigenomics has begun to identify combinatorial profiles of environmental stressors modulating the latency, initiation and progression of specific neurological disorders, and more selective disease biomarkers and graded molecular responses to emerging therapeutic interventions. Pharmacoepigenomic therapies will promote accelerated recovery of impaired and seemingly irrevocably lost cognitive, behavioral, sensorimotor functions through epigenetic reprogramming of endogenous regional neural stem cell fate decisions, targeted tissue remodeling and restoration of neural network integrity, plasticity and connectivity. PMID:18940229

  3. Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study.

    PubMed

    de Almeida, Fernando Antonio; Ciambelli, Giuliano Serafino; Bertoco, André Luz; Jurado, Marcelo Mai; Siqueira, Guilherme Vasconcelos; Bernardo, Eder Augusto; Pavan, Maria Valeria; Gianini, Reinaldo José

    2015-02-01

    In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

  4. Developing new treatments for Alzheimer’s disease

    PubMed Central

    Lyketsos, Constantine G.; Szekely, Christine A.; Mielke, Michelle M.; Rosenberg, Paul B.; Zandi, Peter P.

    2008-01-01

    This synthetic review presents an approach to the use of biomarkers for the development of new treatments for Alzheimer’s disease (AD). After reviewing the process of translation as applied to AD, the paper provides a general update on what is known about the biology of the disease, and highlights currently available treatments. This is followed by a discussion of future drug development for AD emphasizing the roles that biomarkers are likely to play in this process: (1) Define patients who are going to progress rapidly for the purpose of trial enrichment; (2) Differentiate disease and therapeutically relevant AD subtypes; (3) Assess the potential activity of specific therapies in vivo or ex vivo; and (4) Measure the underlying disease state, so as to (a) detect disease and assess drug response in asymptomatic patients, (b) serve as a secondary outcome measures in clinical trials of symptomatic patients, (c) decide if further development of a treatment should be stopped as it is not likely to be effective. Several examples are used to illustrate each biomarker utility in the AD context. PMID:18498669

  5. Guns, germs, and stealing: exploring the link between infectious disease and crime.

    PubMed

    Shrira, Ilan; Wisman, Arnaud; Webster, Gregory

    2013-03-27

    Can variation in crime rates be traced to the threat of infectious disease? Pathogens pose an ongoing challenge to survival, leading humans to adapt defenses to manage this threat. In addition to the biological immune system, humans have psychological and behavioral responses designed to protect against disease. Under persistent disease threat, xenophobia increases and people constrict social interactions to known in-group members. Though these responses reduce disease transmission, they can generate favorable crime conditions in two ways. First, xenophobia reduces inhibitions against harming and exploiting out-group members. Second, segregation into in-group factions erodes people's concern for the welfare of their community and weakens the collective ability to prevent crime. The present study examined the effects of infection incidence on crime rates across the United States. Infection rates predicted violent and property crime more strongly than other crime covariates. Infections also predicted homicides against strangers but not family or acquaintances, supporting the hypothesis that in-group-out-group discrimination was responsible for the infections-crime link. Overall, the results add to evidence that disease threat shapes interpersonal behavior and structural characteristics of groups.

  6. Target Control in Logical Models Using the Domain of Influence of Nodes.

    PubMed

    Yang, Gang; Gómez Tejeda Zañudo, Jorge; Albert, Réka

    2018-01-01

    Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system's state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins, and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in Boolean network models of biomolecular networks. Specifically, we define the domain of influence (DOI) of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence (LDOI) of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose DOI can cover the desired target node states. We perform greedy randomized adaptive search in node state space to find such solutions. We apply our strategy to in silico biological network models of real systems to demonstrate its effectiveness.

  7. The Role of Neutrophils in the Event of Intestinal Inflammation

    PubMed Central

    Mumy, Karen L.; McCormick, Beth A.

    2009-01-01

    The transmigration of polymorphonuclear leukocytes (PMNs; neutrophils) into the intestinal lumen is a classical phenomenon associated with a wide variety of disease states, including those of both pathogenic and autoimmune/idiopathic origin. While PMNs are highly effective at killing invading pathogens by releasing microbiocidal products, excessive or unnecessary release of these substances can cause substantial damage to the intestinal epithelium. Therefore, it is necessary to understand the underlying mechanisms that lure neutrophils into the lumen allowing them to perform their desired functions, so that researchers may begin to identify which processes may be potential targets for inhibiting the transmigration of PMNs during non-infectious states. PMID:19854677

  8. Portal Vein Embolization: State-of-the-Art Technique and Options to Improve Liver Hypertrophy.

    PubMed

    Huang, Steven Y; Aloia, Thomas A

    2017-12-01

    Portal vein embolization (PVE) is associated with a high technical and clinical success rate for induction of future liver remnant hypertrophy prior to surgical resection. The degree of hypertrophy is variable and depends on multiple factors, including technical aspects of the procedure and underlying chronic liver disease. For patients with insufficient liver volume following PVE, adjunctive techniques, such as intra-portal administration of stem cells, dietary supplementation, transarterial embolization, and hepatic vein embolization, are available. Our purpose is to review the state-of-the-art technique associated with high-quality PVE and to discuss options to improve hypertrophy of the future liver remnant.

  9. Protein particulates: another generic form of protein aggregation?

    PubMed

    Krebs, Mark R H; Devlin, Glyn L; Donald, A M

    2007-02-15

    Protein aggregation is a problem with a multitude of consequences, ranging from affecting protein expression to its implication in many diseases. Of recent interest is the specific form of aggregation leading to the formation of amyloid fibrils, structures associated with diseases such as Alzheimer's disease. The ability to form amyloid fibrils is now regarded as a property generic to all polypeptide chains. Here we show that around the isoelectric point a different generic form of aggregation can also occur by studying seven widely different, nonrelated proteins that are also all known to form amyloid fibrils. Under these conditions gels consisting of relatively monodisperse spherical particulates are formed. Although these gels have been described before for beta-lactoglobulin, our results suggest that the formation of particulates in the regime where charge on the molecules is minimal is a common property of all proteins. Because the proteins used here also form amyloid fibrils, we further propose that protein misfolding into clearly defined aggregates is a generic process whose outcome depends solely on the general properties of the state the protein is in when aggregation occurs, rather than the specific amino acid sequence. Thus under conditions of high net charge, amyloid fibrils form, whereas under conditions of low net charge, particulates form. This observation furthermore suggests that the rules of soft matter physics apply to these systems.

  10. Humans as holobionts: implications for prevention and therapy.

    PubMed

    van de Guchte, Maarten; Blottière, Hervé M; Doré, Joël

    2018-05-01

    The human gut microbiota is increasingly recognized for its important or even decisive role in health. As it becomes clear that microbiota and host mutually affect and depend on each other in an intimate relationship, a holistic view of the gut microbiota-host association imposes itself. Ideally, a stable state of equilibrium, homeostasis, is maintained and serves health, but signs are that perturbation of this equilibrium beyond the limits of resilience can propel the system into an alternative stable state, a pre-disease state, more susceptible to the development of chronic diseases. The microbiota-host equilibrium of a large and growing proportion of individuals in Western society may represent such a pre-disease state and explain the explosive development of chronic diseases such as inflammatory bowel disease, obesity, and other inflammatory diseases. These diseases themselves represent other alternative stable states again and are therefore hard to cure. The holistic view of the microbiota-host association where feedback loops between microbiota and host are thought to maintain the system in a stable state-be it a healthy, pre-disease, or disease state-implies that integrated approaches, addressing host processes and microbiota, should be used to treat or prevent (pre-)disease.

  11. Costs of Chronic Diseases at the State Level: The Chronic Disease Cost Calculator

    PubMed Central

    Murphy, Louise B.; Khavjou, Olga A.; Li, Rui; Maylahn, Christopher M.; Tangka, Florence K.; Nurmagambetov, Tursynbek A.; Ekwueme, Donatus U.; Nwaise, Isaac; Chapman, Daniel P.; Orenstein, Diane

    2015-01-01

    Introduction Many studies have estimated national chronic disease costs, but state-level estimates are limited. The Centers for Disease Control and Prevention developed the Chronic Disease Cost Calculator (CDCC), which estimates state-level costs for arthritis, asthma, cancer, congestive heart failure, coronary heart disease, hypertension, stroke, other heart diseases, depression, and diabetes. Methods Using publicly available and restricted secondary data from multiple national data sets from 2004 through 2008, disease-attributable annual per-person medical and absenteeism costs were estimated. Total state medical and absenteeism costs were derived by multiplying per person costs from regressions by the number of people in the state treated for each disease. Medical costs were estimated for all payers and separately for Medicaid, Medicare, and private insurers. Projected medical costs for all payers (2010 through 2020) were calculated using medical costs and projected state population counts. Results Median state-specific medical costs ranged from $410 million (asthma) to $1.8 billion (diabetes); median absenteeism costs ranged from $5 million (congestive heart failure) to $217 million (arthritis). Conclusion CDCC provides methodologically rigorous chronic disease cost estimates. These estimates highlight possible areas of cost savings achievable through targeted prevention efforts or research into new interventions and treatments. PMID:26334712

  12. Modeling the economic outcomes of immuno-oncology drugs: alternative model frameworks to capture clinical outcomes

    PubMed Central

    Gibson, EJ; Begum, N; Koblbauer, I; Dranitsaris, G; Liew, D; McEwan, P; Tahami Monfared, AA; Yuan, Y; Juarez-Garcia, A; Tyas, D; Lees, M

    2018-01-01

    Background Economic models in oncology are commonly based on the three-state partitioned survival model (PSM) distinguishing between progression-free and progressive states. However, the heterogeneity of responses observed in immuno-oncology (I-O) suggests that new approaches may be appropriate to reflect disease dynamics meaningfully. Materials and methods This study explored the impact of incorporating immune-specific health states into economic models of I-O therapy. Two variants of the PSM and a Markov model were populated with data from one clinical trial in metastatic melanoma patients. Short-term modeled outcomes were benchmarked to the clinical trial data and a lifetime model horizon provided estimates of life years and quality adjusted life years (QALYs). Results The PSM-based models produced short-term outcomes closely matching the trial outcomes. Adding health states generated increased QALYs while providing a more granular representation of outcomes for decision making. The Markov model gave the greatest level of detail on outcomes but gave short-term results which diverged from those of the trial (overstating year 1 progression-free survival by around 60%). Conclusion Increased sophistication in the representation of disease dynamics in economic models is desirable when attempting to model treatment response in I-O. However, the assumptions underlying different model structures and the availability of data for health state mapping may be important limiting factors. PMID:29563820

  13. Federally-Assisted Healthcare Coverage among Male State Prisoners with Chronic Health Problems

    PubMed Central

    Rosen, David L.; Grodensky, Catherine A.; Holley, Tara K.

    2016-01-01

    Prisoners have higher rates of chronic diseases such as substance dependence, mental health conditions and infectious disease, as compared to the general population. We projected the number of male state prisoners with a chronic health condition who at release would be eligible or ineligible for healthcare coverage under the Affordable Care Act (ACA). We used ACA income guidelines in conjunction with reported pre-arrest social security benefits and income from a nationally representative sample of prisoners to estimate the number eligible for healthcare coverage at release. There were 643,290 US male prisoners aged 18–64 with a chronic health condition. At release, 73% in Medicaid-expansion states would qualify for Medicaid or tax credits. In non-expansion states, 54% would qualify for tax credits, but 22% (n = 69,827) had incomes of ≤ 100% the federal poverty limit and thus would be ineligible for ACA-mediated healthcare coverage. These prisoners comprise 11% of all male prisoners with a chronic condition. The ACA was projected to provide coverage to most male state prisoners with a chronic health condition; however, roughly 70,000 fall in the “coverage gap” and may require non-routine care at emergency departments. Mechanisms are needed to secure coverage for this at risk group and address barriers to routine utilization of health services. PMID:27479089

  14. Tuberculosis Among Temporary Visa Holders Working in the Tourism Industry - United States, 2012-2014.

    PubMed

    Weinberg, Meghan P; Cherry, Cara; Lipnitz, Julie; Nienstadt, Linus; King-Todd, April; Haddad, Maryam B; Russell, Michelle; Wong, David; Davidson, Peter; McFadden, Jevon; Miller, Corinne

    2016-03-25

    Tuberculosis (TB) is a contagious bacterial disease of global concern. During 2013, an estimated nine million incident TB cases occurred worldwide (1). The majority (82%) were diagnosed in 22 countries, including South Africa and the Philippines, where annual incidence was 860 TB cases per 100,000 persons and 292 TB cases per 100,000 persons, respectively (1). The 2013 TB incidence in the United States was three cases per 100,000 persons (2). Under the Immigration and Nationality Act, TB screening is required for persons seeking permanent residence in the United States (i.e., immigrants and refugees), but it is not routinely required for nonimmigrants who are issued temporary visas for school or work (3). A portion of the U.S. tourism industry relies on temporary visa holders to accommodate seasonal and fluctuating demand for service personnel (4). This report describes three foreign-born persons holding temporary visas who had infectious TB while working at tourist destinations in the United States during 2012-2014. Multiple factors, including dormitory-style housing, transient work patterns, and diagnostic delays might have contributed to increased opportunity for TB transmission. Clinicians in seasonally driven tourist destinations should be aware of the potential for imported TB disease in foreign-born seasonal workers and promptly report suspected cases to health officials.

  15. The impact of new (orphan) drug approvals on premature mortality from rare diseases in the United States and France, 1999-2007.

    PubMed

    Lichtenberg, Frank R

    2013-02-01

    This paper investigates the impact of the introduction of new orphan drugs on premature mortality from rare diseases using longitudinal, disease-level data obtained from a number of major databases. The analysis is performed using data from two countries: the United States (during the period 1999-2006) and France (during the period 2000-2007). For both countries, we estimate models using two alternative definitions of premature mortality, several alternative criteria for inclusion in the set of rare diseases, and several values of the potential lag between new drug approvals and premature mortality reduction. Both the United States and French estimates indicate that, overall, premature mortality from rare diseases is unrelated to the cumulative number of drugs approved 0-2 years earlier but is significantly inversely related to the cumulative number of drugs approved 3-4 years earlier. This delay is not surprising, since most patients probably do not have access to a drug until several years after it has been launched. Although the estimates for the two countries are qualitatively similar, the estimated magnitudes of the US coefficients are about four times as large as the magnitudes of the French coefficients. This may be partly due to greater errors in measuring dates of drug introduction in France. Also, access to new drugs may be more restricted in France than it is in the United States. Our estimates indicate that, in the United States, potential years of life lost to rare diseases before age 65 (PYLL65) declined at an average annual rate of 3.3% and that, in the absence of lagged new drug approvals, PYLL65 would have increased at a rate of 0.9%. Since the US population aged 0-64 was increasing at the rate of 1.0% per year, this means that PYLL65 per person under 65 would have remained approximately constant. The reduction in the US growth rate of PYLL65 attributable to lagged new drug approvals was 4.2%. In France, PYLL65 declined at an average annual rate of 1.8%. The estimates imply that, in the absence of lagged new drug approvals, it would have declined at a rate of 0.6%. The reduction in the French growth rate of PYLL65 attributable to lagged new drug approvals was 1.1%. Earlier access to orphan drugs could result in earlier reductions in premature mortality from rare diseases.

  16. Comparison of survival patterns of northern and southern genotypes of the North American tick Ixodes scapularis (Acari: Ixodidae) under northern and southern conditions

    USGS Publications Warehouse

    Ginsberg, Howard S.; Rulison, Eric L.; Azevedo, Alexandra; Pang, Genevieve C.; Kuczaj, Isis M.; Tsao, Jean I.; LeBrun, Roger A.

    2014-01-01

    BackgroundSeveral investigators have reported genetic differences between northern and southern populations of Ixodes scapularis in North America, as well as differences in patterns of disease transmission. Ecological and behavioral correlates of these genetic differences, which might have implications for disease transmission, have not been reported. We compared survival of northern with that of southern genotypes under both northern and southern environmental conditions in laboratory trials.MethodsSubadult I. scapularis from laboratory colonies that originated from adults collected from deer from several sites in the northeastern, north central, and southern U.S. were exposed to controlled conditions in environmental chambers. Northern and southern genotypes were exposed to light:dark and temperature conditions of northern and southern sites with controlled relative humidities, and mortality through time was recorded.ResultsTicks from different geographical locations differed in survival patterns, with larvae from Wisconsin surviving longer than larvae from Massachusetts, South Carolina or Georgia, when held under the same conditions. In another experiment, larvae from Florida survived longer than larvae from Michigan. Therefore, survival patterns of regional genotypes did not follow a simple north–south gradient. The most consistent result was that larvae from all locations generally survived longer under northern conditions than under southern conditions.ConclusionsOur results suggest that conditions in southern North America are less hospitable than in the north to populations of I. scapularis. Southern conditions might have resulted in ecological or behavioral adaptations that contribute to the relative rarity of I. scapularis borne diseases, such as Lyme borreliosis, in the southern compared to the northern United States.

  17. [Oxygen-dependent energy deficit as related to the problems of ontogenetic development disorders and human sociobiological adaptation (theoretical and applied aspects)].

    PubMed

    Ilyukhina, V A; Kataeva, G V; Korotkov, A D; Chernysheva, E M

    2015-01-01

    The review states and argues theoretical propositions on the pathogenetic role of pre- and perinatal hypoxic-ischemic brain damage in the formation of sustained oxygen-dependent energy deficit underlying in further ontogenesis the following neurobiological abnormalities: a) a decline in the level of health and compensatory-adaptive capacities of the organism, b) disorders of the psycho-speech development and adaptive behavior in children, c) early development of neuropsychic diseases, g) addition of other types of brain energy metabolism (including glucose metabolism) disorders in chronic polyetiologic diseases young and middle-aged individuals. We highlight and theoretically substantiate the integrated physiological parameters of the oxygen-dependent energy deficit types. We address the features of abnormalities in neuroreflectory and neurohumora regulatory mechanisms of the wakefulness level and its vegetative and hemodynamic provision in different types of energy deficit in children with DSMD, ADHD and school maladjustment. The use of the state-of-the-art neuroimaging techniques significantly increased the possibility of the disintegration of regulatory processes and cognitive functions in children with psycho-speech delays and in a wide range of chronic polyetiologic diseases.

  18. Alterations in protein phosphorylation in the amygdala of the 5XFamilial Alzheimer's disease animal model.

    PubMed

    Yang, Eun-Jeong; Mahmood, Usman; Kim, Hyunju; Choi, Moonseok; Choi, Yunjung; Lee, Jean-Pyo; Chang, Moon-Jeong; Kim, Hye-Sun

    2017-04-01

    Alzheimer's disease is the most common disease underlying dementia in humans. Two major neuropathological hallmarks of AD are neuritic plaques primarily composed of amyloid beta peptide and neurofibrillary tangles primarily composed of hyperphosphorylated tau. In addition to impaired memory function, AD patients often display neuropsychiatric symptoms and abnormal emotional states such as confusion, delusion, manic/depressive episodes and altered fear status. Brains from AD patients show atrophy of the amygdala which is involved in fear expression and emotional processing as well as hippocampal atrophy. However, which molecular changes are responsible for the altered emotional states observed in AD remains to be elucidated. Here, we observed that the fear response as assessed by evaluating fear memory via a cued fear conditioning test was impaired in 5XFamilial AD (5XFAD) mice, an animal model of AD. Compared to wild-type mice, 5XFAD mice showed changes in the phosphorylation of twelve proteins in the amygdala. Thus, our study provides twelve potential protein targets in the amygdala that may be responsible for the impairment in fear memory in AD. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  19. The antimasturbation crusade in antebellum American medicine.

    PubMed

    Hodges, Frederick M

    2005-09-01

    The antimasturbation fervor that swept through the English-speaking world during the 19th century raged with particular intensity and unequaled duration in the United States. American medical leaders were convinced that masturbation was the underlying cause of nearly all social problems and diseases. Even after the discovery and general acceptance of the germ theory of disease in the late 19th century, the U.S. medical establishment continued to maintain well into the middle of the 20th century that masturbation was both a pathological act and a cause of mental and physical disease. This article explores the dominant themes in the medical doctrines about masturbation that prevailed in the first half of the 19th century, by examining the case reports of five prominent American physicians: Benjamin Rush, Samuel Bayard Woodward, Alfred Hitchcock, Alonzo Garwood, and Edward H. Dixon.

  20. [Practice guideline neuroendocrine tumors - AWMF-Reg. 021-27].

    PubMed

    2018-06-01

    This guideline was created for the first time and is intended as a practical aid for the diagnosis and therapy of neuroendocrine tumors. The aim is to represent the current state of science, promote the recognition of the disease and improve the treatment of patients. The guideline was created under the leadership of the DGVS and with participation of neighbouring scientific societies. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Patient Care Outcomes: Implications for the Military Health Services Systems

    DTIC Science & Technology

    1991-05-05

    understanding the crisis in health care costs is a sense of the effects of the aging population in the United States on the health care system. People ...are living longer. Consequently, the time o,,r which people 2 qualify for health care coverage under Medicare has also increased. Not surprisingly, the...increased life span has two concomitant health care implications. First, people are more likely to develop and live with chronic diseases that

  2. Agroterrorism as a Potential Military Threat

    DTIC Science & Technology

    2010-03-01

    paper are those of the author and do not reflect the official policy or position of the US government or the Department of Defense. In Accordance...priority, and lastly category C includes (but not limited to) such agents as the West Nile fever, Hantavirus , and new and emerging diseases. 44 This is...entirety states, “Whoever, except in cases and under circumstances expressly authorized by the Constitution or Act of Congress, willfully uses any

  3. 9 CFR 82.19 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... bacterial disease of birds and poultry, characterized by respiratory and systemic infection. The disease is... disease. Interstate. From one State into or through any other State. Moved. Shipped, transported or...- and poultry-disease control and eradication programs. State representative. An individual employed in...

  4. Access to essential medicines: a Hobbesian social contract approach.

    PubMed

    Ashcroft, Richard E

    2005-05-01

    Medicines that are vital for the saving and preserving of life in conditions of public health emergency or endemic serious disease are known as essential medicines. In many developing world settings such medicines may be unavailable, or unaffordably expensive for the majority of those in need of them. Furthermore, for many serious diseases (such as HIV/AIDS and tuberculosis) these essential medicines are protected by patents that permit the patent-holder to operate a monopoly on their manufacture and supply, and to price these medicines well above marginal cost. Recent international legal doctrine has placed great stress on the need to globalise intellectual property rights protections, and on the rights of intellectual property rights holders to have their property rights enforced. Although international intellectual property rights law does permit compulsory licensing of protected inventions in the interests of public health, the use of this right by sovereign states has proved highly controversial. In this paper I give an argument in support of states' sovereign right to expropriate private intellectual property in conditions of public health emergency. This argument turns on a social contract argument for the legitimacy of states. The argument shows, further, that under some circumstances states are not merely permitted compulsory to license inventions, but are actually obliged to do so, on pain of failure of their legitimacy as sovereign states. The argument draws freely on a loose interpretation of Thomas Hobbes's arguments in his Leviathan, and on an analogy between his state of War and the situation of public health disasters.

  5. Recent Advances in Type-2-Cell-Mediated Immunity: Insights from Helminth Infection.

    PubMed

    Harris, Nicola L; Loke, P'ng

    2017-12-19

    Type-2-cell-mediated immune responses play a critical role in mediating both host-resistance and disease-tolerance mechanisms during helminth infections. Recently, type 2 cell responses have emerged as major regulators of tissue repair and metabolic homeostasis even under steady-state conditions. In this review, we consider how studies of helminth infection have contributed toward our expanding cellular and molecular understanding of type-2-cell-mediated immunity, as well as new areas such as the microbiome. By studying how these successful parasites form chronic infections without overt pathology, we are gaining additional insights into allergic and inflammatory diseases, as well as normal physiology. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Neutrophils in Homeostasis, Immunity, and Cancer.

    PubMed

    Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

    2017-01-17

    Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Implications of cellular models of dopamine neurons for disease

    PubMed Central

    Evans, Rebekah C.; Oster, Andrew M.; Pissadaki, Eleftheria K.; Drion, Guillaume; Kuznetsov, Alexey S.; Gutkin, Boris S.

    2016-01-01

    This review addresses the present state of single-cell models of the firing pattern of midbrain dopamine neurons and the insights that can be gained from these models into the underlying mechanisms for diseases such as Parkinson's, addiction, and schizophrenia. We will explain the analytical technique of separation of time scales and show how it can produce insights into mechanisms using simplified single-compartment models. We also use morphologically realistic multicompartmental models to address spatially heterogeneous aspects of neural signaling and neural metabolism. Separation of time scale analyses are applied to pacemaking, bursting, and depolarization block in dopamine neurons. Differences in subpopulations with respect to metabolic load are addressed using multicompartmental models. PMID:27582295

  8. Recipient selection process and listing for lung transplantation

    PubMed Central

    Dupont, Lieven; Yserbyt, Jonas; Schaevers, Veronique; Van Raemdonck, Dirk; Neyrinck, Arne; Vos, Robin

    2017-01-01

    Lung transplantation remains the ultimate treatment option for selected patients with end-stage (cardio) pulmonary disease. Given the current organ shortage, it is without any doubt that careful selection of potential transplant candidates is essential as this may greatly influence survival after the procedure. In this paper, we will review the current guidelines for referral and listing of lung transplant candidates in general, and in more depth for the specific underlying diseases. Needless to state that these are not absolute guidelines, and that decisions depend upon center’s activity, waiting list, etc. Therefore, every patient should be discussed with the transplant center before any definite decision is made to accept or decline a patient for lung transplantation. PMID:29221322

  9. [Embryonic stem cells. Future perspectives].

    PubMed

    Groebner, M; David, R; Franz, W M

    2006-05-01

    Embryonic stem cells (ES cells) are able to differentiate into any cell type, and therefore represent an excellent source for cellular replacement therapies in the case of widespread diseases, for example heart failure, diabetes, Parkinson's disease and spinal cord injury. A major prerequisite for their efficient and safe clinical application is the availability of pure populations for direct cell transplantation or tissue engineering as well as the immunological compatibility of the transplanted cells. The expression of human surface markers under the control of cell type specific promoters represents a promising approach for the selection of cardiomyocytes and other cell types for therapeutic applications. The first human clinical trial using ES cells will start in the United States this year.

  10. Mechanisms of Cachexia in Chronic Disease States

    PubMed Central

    Yoshida, Tadashi; Delafontaine, Patrice

    2015-01-01

    Sarcopenia and cachexia are muscle wasting syndromes associated with aging and with many chronic diseases such as congestive heart failure (CHF), diabetes, cancer, chronic obstructive pulmonary disease and chronic kidney disease (CKD). While mechanisms are complex these conditions are often accompanied by elevated angiotensin II (Ang II). Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme (ACE) inhibitor treatment improves weight loss. We found that Ang II infusion in rodents leads to skeletal muscle wasting. Ang II increases cytokines and circulating hormones such as tumor necrosis factor-α, interleukin-6, serum amyloid-A and glucocorticoids, which regulate muscle protein synthesis and degradation. Ang II-induced muscle wasting is caused by alterations in insulin-like growth factor-1 signaling, enhanced muscle protein breakdown via the ubiquitin-proteasome system, and decreased appetite resulting from downregulation of hypothalamic orexigenic neuropeptides such as Npy and orexin. Ang II also inhibits 5′ AMP-activated protein kinase (AMPK) activity and disrupts normal energy balance via activation of AMPK phosphatase PP2Cα. Furthermore, Ang II inhibits skeletal muscle stem (satellite) cell proliferation, leading to lowered muscle regenerative capacity. Distinct satellite cell angiotensin receptor subtypes have different effects on different stages of differentiation and are critical for regulation of muscle regeneration. These data suggest that the renin-angiotensin system (RAS) plays a critical role in mechanisms underlying cachexia in chronic disease states, and is a promising target for the treatment of muscle atrophy in patients with diseases such as CHF and CKD. PMID:26083652

  11. Mechanisms of Cachexia in Chronic Disease States.

    PubMed

    Yoshida, Tadashi; Delafontaine, Patrice

    2015-10-01

    Sarcopenia and cachexia are muscle wasting syndromes associated with aging and with many chronic diseases, such as congestive heart failure (CHF), diabetes, cancer, chronic obstructive pulmonary disease and chronic kidney disease (CKD). While mechanisms are complex, these conditions are often accompanied by elevated angiotensin II (Ang II). Patients with advanced CHF or CKD often have increased Ang II levels and cachexia, and angiotensin-converting enzyme inhibitor treatment improves weight loss. It was found that Ang II infusion in rodents leads to skeletal muscle wasting. Ang II increases cytokines and circulating hormones, such as tumor necrosis factor-α, interleukin-6, serum amyloid-A and glucocorticoids, which regulate muscle protein synthesis and degradation. Ang II-induced muscle wasting is caused by alterations in insulin-like growth factor-1 signaling, enhanced muscle protein breakdown via the ubiquitin-proteasome system and decreased appetite resulting from the downregulation of hypothalamic orexigenic neuropeptides, such as Npy and orexin. Ang II also inhibits 5' adenosine monophosphate-activated protein kinase activity and disrupts normal energy balance via the activation of 5' adenosine monophosphate-activated protein kinase phosphatase PP2Cα. Furthermore, Ang II inhibits skeletal muscle stem (satellite) cell proliferation, leading to lowered muscle regenerative capacity. Distinct satellite cell angiotensin receptor subtypes have different effects on different stages of differentiation and are critical for the regulation of muscle regeneration. These data suggest that the renin-angiotensin system plays a critical role in mechanisms underlying cachexia in chronic disease states, and it is a promising target for the treatment of muscle atrophy in patients with diseases such as CHF and CKD.

  12. Hierarchical Interactions Model for Predicting Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD) Conversion

    PubMed Central

    Li, Han; Liu, Yashu; Gong, Pinghua; Zhang, Changshui; Ye, Jieping

    2014-01-01

    Identifying patients with Mild Cognitive Impairment (MCI) who are likely to convert to dementia has recently attracted increasing attention in Alzheimer's disease (AD) research. An accurate prediction of conversion from MCI to AD can aid clinicians to initiate treatments at early stage and monitor their effectiveness. However, existing prediction systems based on the original biosignatures are not satisfactory. In this paper, we propose to fit the prediction models using pairwise biosignature interactions, thus capturing higher-order relationship among biosignatures. Specifically, we employ hierarchical constraints and sparsity regularization to prune the high-dimensional input features. Based on the significant biosignatures and underlying interactions identified, we build classifiers to predict the conversion probability based on the selected features. We further analyze the underlying interaction effects of different biosignatures based on the so-called stable expectation scores. We have used 293 MCI subjects from Alzheimer's Disease Neuroimaging Initiative (ADNI) database that have MRI measurements at the baseline to evaluate the effectiveness of the proposed method. Our proposed method achieves better classification performance than state-of-the-art methods. Moreover, we discover several significant interactions predictive of MCI-to-AD conversion. These results shed light on improving the prediction performance using interaction features. PMID:24416143

  13. Initial condition of stochastic self-assembly

    NASA Astrophysics Data System (ADS)

    Davis, Jason K.; Sindi, Suzanne S.

    2016-02-01

    The formation of a stable protein aggregate is regarded as the rate limiting step in the establishment of prion diseases. In these systems, once aggregates reach a critical size the growth process accelerates and thus the waiting time until the appearance of the first critically sized aggregate is a key determinant of disease onset. In addition to prion diseases, aggregation and nucleation is a central step of many physical, chemical, and biological process. Previous studies have examined the first-arrival time at a critical nucleus size during homogeneous self-assembly under the assumption that at time t =0 the system was in the all-monomer state. However, in order to compare to in vivo biological experiments where protein constituents inherited by a newly born cell likely contain intermediate aggregates, other possibilities must be considered. We consider one such possibility by conditioning the unique ergodic size distribution on subcritical aggregate sizes; this least-informed distribution is then used as an initial condition. We make the claim that this initial condition carries fewer assumptions than an all-monomer one and verify that it can yield significantly different averaged waiting times relative to the all-monomer condition under various models of assembly.

  14. Trichomonas vaginalis: Clinical relevance, pathogenicity and diagnosis.

    PubMed

    Edwards, Thomas; Burke, Patricia; Smalley, Helen; Hobbs, Glyn

    2016-05-01

    Trichomonas vaginalis is the etiological agent of trichomoniasis, the most prevalent non-viral sexually transmitted disease worldwide. Trichomoniasis is a widespread, global health concern and occurring at an increasing rate. Infections of the female genital tract can cause a range of symptoms, including vaginitis and cervicitis, while infections in males are generally asymptomatic. The relatively mild symptoms, and lack of evidence for any serious sequelae, have historically led to this disease being under diagnosed, and under researched. However, growing evidence that T. vaginalis infection is associated with other disease states with high morbidity in both men and women has increased the efforts to diagnose and treat patients harboring this parasite. The pathology of trichomoniasis results from damage to the host epithelia, caused by a variety of processes during infection and recent work has highlighted the complex interactions between the parasite and host, commensal microbiome and accompanying symbionts. The commercial release of a number of nucleic acid amplification tests (NAATs) has added to the available diagnostic options. Immunoassay based Point of Care testing is currently available, and a recent initial evaluation of a NAAT Point of Care system has given promising results, which would enable testing and treatment in a single visit.

  15. Johnson v. Superior Court.

    PubMed

    2000-01-01

    Court Decision: 95 California Reporter, 2d Series 864; 18 May 2000 (date of decision). The Court of Appeal, Second District held that parents and their child, conceived with sperm from an anonymous donor, could compel the donor's deposition and production of documents in an effort to discover information relevant to their action against the sperm bank, California Cryobank, Inc. Cryobank sold Diane and Ronald Johnson sperm that it falsely claimed was fully tested and genetically screened. The sperm, from donor John Doe, genetically transmitted a kidney disease to the Johnson's child. The Johnsons sought information and a deposition from Doe in their action against Cryobank; Doe refused. The court first held that communications between Cryobank and Doe were not protected under the physician-patient privilege because Doe was not a patient and he visited Cryobank with the sole purpose of selling his sperm. The court also found that the agreement between Cryobank and the Johnsons did not preclude the disclosure of Doe's identity under all circumstances because such preclusion is against public policy. Under state law, parties are allowed to inspect insemination records under certain circumstances. To prevent inspection under all circumstances conflicts with a compelling state interest in the health and welfare of children. Finally, the court did not find its holding in violation of Doe's right of privacy because, although Doe's medical records are protected under the right of privacy, compelling state interests in relevant disclosure in court proceedings, seeking the truth in court proceedings, and ensuring full redress of those injured override Doe's interest. The court specified that Doe's identity need not be automatically disclosed, and suggested the trial court construct an order protecting Doe's identity as much as possible.

  16. Happiness and neurological diseases.

    PubMed

    Barak, Yoram; Achiron, Anat

    2009-04-01

    Happiness is an emotional state reflecting positive feelings and satisfaction with life, which, as an outcome in disease states or as an end point in clinical trials, is a neglected concept in most therapeutic areas. In neurological disease, happiness is important as it can be diminished either as a direct result of damage to neuronal tissue or as a reaction to a poor prognosis. The monitoring and maintenance of happiness and wellbeing have historically been considered to be peripheral to medicine. However, as happiness interacts with the patient's physical health, it is an important parameter to assess alongside all aspects of any given disease. Happiness provides a reliable overview of the patient's general status over and above standard parameters for quality of life, and is more wide-ranging than the narrow measures of disease activity or treatment efficacy that are the focus of most clinical trials. In many studies, happiness has been associated with health and success in most areas of life, including performance at work, sporting achievement and social functioning. For approximately a decade, previously studied aspects of psychology have been grouped under the label of positive psychology (PoP). Principles of this discipline are now being used to guide some treatments in neurological and psychiatric diseases. PoP aims to define patient wellbeing in scientific terms and to increase understanding of happiness, meaning in life, resilience and character strengths, as well as to determine how this knowledge can be applied clinically to promote health. Some evidence has emerged recently suggesting that improvements in patient status can result from interventions to improve the patient's level of happiness in diseases, including epilepsy, Huntington's disease, multiple sclerosis, Parkinson's disease and stroke. Several effective approaches to increase happiness employ activities to engage and stimulate patients who might otherwise be unoccupied and isolated. In addition, specific interventions to increase happiness developed by PoP clinicians have demonstrated efficacy and validity. Several measurement scales now exist that reliably measure happiness as a long-term state, rather than as a fluctuating condition resulting from prevailing mood. These enable the use of happiness as an end point in clinical trials. As happiness becomes increasingly accepted as an important consideration in neurological disease, it is likely to be monitored more extensively, with measures to raise happiness levels being taken as an effective means of improving patient outcomes.

  17. Impact of oxygen availability on body weight management.

    PubMed

    Quintero, P; Milagro, F I; Campión, J; Martínez, J A

    2010-05-01

    Obesity is nowadays a major public health problem. The World Health Organization reported that globally 400 million adults are obese, and the situation seems to raise in the future. Furthermore, obesity is a major risk factor for a number of chronic diseases such as type 2 diabetes, cardiovascular diseases and the metabolic syndrome. Interestingly, several studies have reported that appetite suppression and body weight loss are frequently observed at high altitude. This observation has opened some possibilities for losing weight under hypoxia or living in altitude. Nevertheless, the triggering mechanisms for the decrease in energy intake in hypoxic conditions still remain unclear as well as the impact on body mass components. On the other hand, obese subjects often present a chronic inflammatory state on the adipose tissue that might have a strong relationship with onset and development of obesity-related diseases. Thus, it has been consistently reported that adipose tissue of obese subjects is poorly oxygenated and that this hypoxia state is a new potential risk factor for the chronic inflammation in obesity. In this sense, oxygen therapy is a common technique used in current medicine for the treatment of several diseases, while animal studies have demonstrated that treatment with hyperoxia produces some beneficial effects in different diseases related with lack of oxygen in several organs. In this article, we review the role of oxygen availability in body weight homeostasis and hypothesize the possible applicability of hypoxia and hyperoxia for the treatment of obesity and related disorders.

  18. Modeling oscillatory dynamics in brain microcircuits as a way to help uncover neurological disease mechanisms: A proposal

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

    Skinner, F. K.; Department of Medicine; Department of Physiology, University of Toronto Medical Sciences Building, 3rd Floor, 1 King's College Circle, Toronto, Ontario M5S 1A8

    There is an undisputed need and requirement for theoretical and computational studies in Neuroscience today. Furthermore, it is clear that oscillatory dynamical output from brain networks is representative of various behavioural states, and it is becoming clear that one could consider these outputs as measures of normal and pathological brain states. Although mathematical modeling of oscillatory dynamics in the context of neurological disease exists, it is a highly challenging endeavour because of the many levels of organization in the nervous system. This challenge is coupled with the increasing knowledge of cellular specificity and network dysfunction that is associated with disease.more » Recently, whole hippocampus in vitro preparations from control animals have been shown to spontaneously express oscillatory activities. In addition, when using preparations derived from animal models of disease, these activities show particular alterations. These preparations present an opportunity to address challenges involved with using models to gain insight because of easier access to simultaneous cellular and network measurements, and pharmacological modulations. We propose that by developing and using models with direct links to experiment at multiple levels, which at least include cellular and microcircuit, a cycling can be set up and used to help us determine critical mechanisms underlying neurological disease. We illustrate our proposal using our previously developed inhibitory network models in the context of these whole hippocampus preparations and show the importance of having direct links at multiple levels.« less

  19. Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism

    PubMed Central

    König, Matthias; Bulik, Sascha; Holzhütter, Hermann-Georg

    2012-01-01

    Despite the crucial role of the liver in glucose homeostasis, a detailed mathematical model of human hepatic glucose metabolism is lacking so far. Here we present a detailed kinetic model of glycolysis, gluconeogenesis and glycogen metabolism in human hepatocytes integrated with the hormonal control of these pathways by insulin, glucagon and epinephrine. Model simulations are in good agreement with experimental data on (i) the quantitative contributions of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization under varying physiological states. (ii) the time courses of postprandial glycogen storage as well as glycogen depletion in overnight fasting and short term fasting (iii) the switch from net hepatic glucose production under hypoglycemia to net hepatic glucose utilization under hyperglycemia essential for glucose homeostasis (iv) hormone perturbations of hepatic glucose metabolism. Response analysis reveals an extra high capacity of the liver to counteract changes of plasma glucose level below 5 mM (hypoglycemia) and above 7.5 mM (hyperglycemia). Our model may serve as an important module of a whole-body model of human glucose metabolism and as a valuable tool for understanding the role of the liver in glucose homeostasis under normal conditions and in diseases like diabetes or glycogen storage diseases. PMID:22761565

  20. Surveillance for Waterborne Disease Outbreaks Associated with Drinking Water, United States 2009-2010

    EPA Science Inventory

    Despite advancements in water management and sanitation, waterborne disease outbreaks continue to occur in the United States. CDC collects data on waterborne disease outbreaks submitted from all states and territories* through the Waterborne Disease and Outbreak Surveillance Syst...

  1. A pharmacy practice laboratory exercise to apply biochemistry concepts.

    PubMed

    Harrold, Marc W; McFalls, Marsha A

    2010-10-11

    To develop exercises that allow pharmacy students to apply foundational knowledge discussed in a first-professional year (P1) biochemistry course to specific disease states and patient scenarios. A pharmacy practice laboratory exercise was developed to accompany a lecture sequence pertaining to purine biosynthesis and degradation. The assignment required students to fill a prescription, provide patient counseling tips, and answer questions pertaining to the disease state, the underlying biochemical problem, and the prescribed medication. Students were graded on the accuracy with which they filled the prescription, provided patient counseling, and answered the questions provided. Overall, students displayed mastery in all of these areas. Additionally, students completed a course survey on which they rated this exercise favorably, noting that it helped them to integrate basic science concepts and pharmacy practice. A laboratory exercise provided an opportunity for P1 students to apply foundational pharmacy knowledge to a patient case and can serve as a template for the design of additional exercises.

  2. [Psychoemotional stress and somatic diseases in veterans of special risk units].

    PubMed

    Alishev, N V; Tsygan, V N; Drabkin, B A; Apchel, V Ia; Nikolaeva, N A; Tarumov, A V; Fesiun, A D; Fedoseev, V M

    2008-01-01

    Participants of nuclear-powered submarine accident liquidation and special risk units' veterans participating in surface nuclear weapon tests as well as in liquidation of their consequences have been examined. It has been established that functional state of this category of people is difficult to interpret only in the context of radioactive irradiation effect or injuring stress factor exposure. This state is determined by a complex of psychotraumatic factors tending to become aggravated and characterizing by their individual significance and absolute or relative insolvability. In most representatives of this category the disease is manifested by psychopathologic syndrome of neurotic disorders (low spirits, emotional lability, asthenia, anxiety) and somatic disturbances as dysfunction of the cardiovascular, respiratory, digestive and other systems. The results obtained provide the pathogenetic substantiation of efficient ways and methods for rehabilitation of the special risk units' veterans. The data prove the necessity of appropriate correction of cardiovascular disorders in practically healthy servicemen residing under conditions of psychoemotional tension.

  3. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.

    PubMed

    Falcone, Marco; Concia, Ercole; Giusti, Massimo; Mazzone, Antonino; Santini, Claudio; Stefani, Stefania; Violi, Francesco

    2016-08-01

    Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed.

  4. Explosive genetic evidence for explosive human population growth

    PubMed Central

    Gao, Feng; Keinan, Alon

    2016-01-01

    The advent of next-generation sequencing technology has allowed the collection of vast amounts of genetic variation data. A recurring discovery from studying larger and larger samples of individuals had been the extreme, previously unexpected, excess of very rare genetic variants, which has been shown to be mostly due to the recent explosive growth of human populations. Here, we review recent literature that inferred recent changes in population size in different human populations and with different methodologies, with many pointing to recent explosive growth, especially in European populations for which more data has been available. We also review the state-of-the-art methods and software for the inference of historical population size changes that lead to these discoveries. Finally, we discuss the implications of recent population growth on personalized genomics, on purifying selection in the non-equilibrium state it entails and, as a consequence, on the genetic architecture underlying complex disease and the performance of mapping methods in discovering rare variants that contribute to complex disease risk. PMID:27710906

  5. Mechanism of erosion of nanostructured porous silicon drug carriers in neoplastic tissues

    PubMed Central

    Tzur-Balter, Adi; Shatsberg, Zohar; Beckerman, Margarita; Segal, Ester; Artzi, Natalie

    2015-01-01

    Nanostructured porous silicon (PSi) is emerging as a promising platform for drug delivery owing to its biocompatibility, degradability and high surface area available for drug loading. The ability to control PSi structure, size and porosity enables programming its in vivo retention, providing tight control over embedded drug release kinetics. In this work, the relationship between the in vitro and in vivo degradation of PSi under (pre)clinically relevant conditions, using breast cancer mouse model, is defined. We show that PSi undergoes enhanced degradation in diseased environment compared with healthy state, owing to the upregulation of reactive oxygen species (ROS) in the tumour vicinity that oxidize the silicon scaffold and catalyse its degradation. We further show that PSi degradation in vitro and in vivo correlates in healthy and diseased states when ROS-free or ROS-containing media are used, respectively. Our work demonstrates that understanding the governing mechanisms associated with specific tissue microenvironment permits predictive material performance. PMID:25670235

  6. Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico.

    PubMed

    Larsen, Christopher P; Beggs, Marjorie L; Wilson, Jon D; Lathrop, Sarah L

    2016-06-01

    Leukocyte chemotactic factor 2 (LECT2) amyloidosis is one of the most recently described types of amyloidosis. Since its description, it has been found to be one the most common types of amyloidosis in large series of amyloid cases involving the kidney and liver in the United States, where it primarily affects patients of Hispanic ethnicity. We sought to investigate the prevalence of this disease among Hispanic adult decedents who had an autopsy performed at the New Mexico Office of the Medical Investigator and determine the organ distribution of amyloid deposition. LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanic decedents. It was consistently deposited in the liver, spleen, adrenals, and lungs but did not involve the myocardium or brain. LECT2 amyloidosis is likely not rare among Hispanics in the Southwest United States and could represent an important but under-recognized etiology of chronic kidney disease in this population.

  7. [Schistosomiasis: reproduction and expansion of the endemia to the state of Pernambuco in Brazil].

    PubMed

    Barbosa, C S; da Silva, C B; Barbosa, F S

    1996-12-01

    Schistosomiasis mansoni can be considered an important public health problem in Northeastern Brazil, in spite of the reduction in the prevalence of the hepatosplenic clinical forms which have been attributed to the large scale use of chemotherapy in this country. However, the rise in the prevalence rates and the spread of this endemic disease to new areas show that schistosomiasis is assuming its must cruel expression: less lethal but more greatly incapacitating in terms of irreversible physical and moral damage to human beings. The state of Pernambuco presents growing rates for schistosomiasis infection in humans. The epidemiological profile of this disease displays high and consistent prevalence rates (up to 80%) in rural areas, and new cases of acute infection on the coast, where schistosomiasis has recently been introduced. The reproduction and expansion of this endemic disease can be better understood on the basic of a conception of structural and historical causation. The disease construction process should be reconstructed in the light of biological as well as the social, political and cultural factors which are jointly responsible for the present endemic situation. Within that frame work, the historical and socioeconomic features that interact with the parasite and give rise to the present proportions of the schistosomiasis epidemic in Pernambuco are discussed. The mode of occupation and use of the land, unemployment, under-nutrition, migration, etc., raise the question of the growing difficulties confronting the control of the disease, both in rural areas where populations are extremely mobile as well as in the poorly organized urban population. Epidemiological investigation is fulfilling its role in its attempts to understand the complex relationships of an intrinsecally social nature of the health/disease process between health problems and the quality of life for the purpose of producing consistent disease control models.

  8. LAMP-2 deficiency leads to hippocampal dysfunction but normal clearance of neuronal substrates of chaperone-mediated autophagy in a mouse model for Danon disease.

    PubMed

    Rothaug, Michelle; Stroobants, Stijn; Schweizer, Michaela; Peters, Judith; Zunke, Friederike; Allerding, Mirka; D'Hooge, Rudi; Saftig, Paul; Blanz, Judith

    2015-01-31

    The Lysosomal Associated Membrane Protein type-2 (LAMP-2) is an abundant lysosomal membrane protein with an important role in immunity, macroautophagy (MA) and chaperone-mediated autophagy (CMA). Mutations within the Lamp2 gene cause Danon disease, an X-linked lysosomal storage disorder characterized by (cardio)myopathy and intellectual dysfunction. The pathological hallmark of this disease is an accumulation of glycogen and autophagic vacuoles in cardiac and skeletal muscle that, along with the myopathy, is also present in LAMP-2-deficient mice. Intellectual dysfunction observed in the human disease suggests a pivotal role of LAMP-2 within brain. LAMP-2A, one specific LAMP-2 isoform, was proposed to be important for the lysosomal degradation of selective proteins involved in neurodegenerative diseases such as Huntington's and Parkinson's disease. To elucidate the neuronal function of LAMP-2 we analyzed knockout mice for neuropathological changes, MA and steady-state levels of CMA substrates. The absence of LAMP-2 in murine brain led to inflammation and abnormal behavior, including motor deficits and impaired learning. The latter abnormality points to hippocampal dysfunction caused by altered lysosomal activity, distinct accumulation of p62-positive aggregates, autophagic vacuoles and lipid storage within hippocampal neurons and their presynaptic terminals. The absence of LAMP-2 did not apparently affect MA or steady-state levels of selected CMA substrates in brain or neuroblastoma cells under physiological and prolonged starvation conditions. Our data contribute to the understanding of intellectual dysfunction observed in Danon disease patients and highlight the role of LAMP-2 within the central nervous system, particularly the hippocampus.

  9. Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

    PubMed

    Dey-Rao, Rama; Sinha, Animesh A

    2017-01-28

    Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address a major gap in knowledge regarding the systemic changes underlying skin-specific manifestation of vitiligo. Several transcriptional "hot spots" observed in both environments offer prioritized targets for identifying disease risk genes. Finally, within the transcriptional framework of VL, we identify five novel molecules (STAT1, PRKCD, PTPN6, MYC and FGFR2) that lend themselves to being targeted by drugs for future potential VL-therapy.

  10. Cardiomyocyte-Specific Telomere Shortening is a Distinct Signature of Heart Failure in Humans.

    PubMed

    Sharifi-Sanjani, Maryam; Oyster, Nicholas M; Tichy, Elisia D; Bedi, Kenneth C; Harel, Ofer; Margulies, Kenneth B; Mourkioti, Foteini

    2017-09-07

    Telomere defects are thought to play a role in cardiomyopathies, but the specific cell type affected by the disease in human hearts is not yet identified. The aim of this study was to systematically evaluate the cell type specificity of telomere shortening in patients with heart failure in relation to their cardiac disease, age, and sex. We studied cardiac tissues from patients with heart failure by utilizing telomere quantitative fluorescence in situ hybridization, a highly sensitive method with single-cell resolution. In this study, total of 63 human left ventricular samples, including 37 diseased and 26 nonfailing donor hearts, were stained for telomeres in combination with cardiomyocyte- or α-smooth muscle cell-specific markers, cardiac troponin T, and smooth muscle actin, respectively, and assessed for telomere length. Patients with heart failure demonstrate shorter cardiomyocyte telomeres compared with nonfailing donors, which is specific only to cardiomyocytes within diseased human hearts and is associated with cardiomyocyte DNA damage. Our data further reveal that hypertrophic hearts with reduced ejection fraction exhibit the shortest telomeres. In contrast to other reported cell types, no difference in cardiomyocyte telomere length is evident with age. However, under the disease state, telomere attrition manifests in both young and older patients with cardiac hypertrophy. Finally, we demonstrate that cardiomyocyte-telomere length is better sustained in women than men under diseased conditions. This study provides the first evidence of cardiomyocyte-specific telomere shortening in heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  11. Ability to monitor driving under the influence of marijuana among non-fatal motor-vehicle crashes: An evaluation of the Colorado electronic accident reporting system.

    PubMed

    Peterson, Alexis B; Sauber-Schatz, Erin K; Mack, Karin A

    2018-06-01

    As more states legalize medical/recreational marijuana use, it is important to determine if state motor-vehicle surveillance systems can effectively monitor and track driving under the influence (DUI) of marijuana. This study assessed Colorado's Department of Revenue motor-vehicle crash data system, Electronic Accident Reporting System (EARS), to monitor non-fatal crashes involving driving under the influence (DUI) of marijuana. Centers for Disease Control and Prevention guidelines on surveillance system evaluation were used to assess EARS' usefulness, flexibility, timeliness, simplicity, acceptability, and data quality. We assessed system components, interviewed key stakeholders, and analyzed completeness of Colorado statewide 2014 motor-vehicle crash records. EARS contains timely and complete data, but does not effectively monitor non-fatal motor-vehicle crashes related to DUI of marijuana. Information on biological sample type collected from drivers and toxicology results were not recorded into EARS; however, EARS is a flexible system that can incorporate new data without increasing surveillance system burden. States, including Colorado, could consider standardization of drug testing and mandatory reporting policies for drivers involved in motor-vehicle crashes and proactively address the narrow window of time for sample collection to improve DUI of marijuana surveillance. Practical applications: The evaluation of state motor-vehicle crash systems' ability to capture crashes involving drug impaired driving (DUID) is a critical first step for identifying frequency and risk factors for crashes related to DUID. Published by Elsevier Ltd.

  12. Understanding Neurological Disease Mechanisms in the Era of Epigenetics

    PubMed Central

    Qureshi, Irfan A.; Mehler, Mark F.

    2015-01-01

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

  13. Genetic-based prediction of disease traits: prediction is very difficult, especially about the future†

    PubMed Central

    Schrodi, Steven J.; Mukherjee, Shubhabrata; Shan, Ying; Tromp, Gerard; Sninsky, John J.; Callear, Amy P.; Carter, Tonia C.; Ye, Zhan; Haines, Jonathan L.; Brilliant, Murray H.; Crane, Paul K.; Smelser, Diane T.; Elston, Robert C.; Weeks, Daniel E.

    2014-01-01

    Translation of results from genetic findings to inform medical practice is a highly anticipated goal of human genetics. The aim of this paper is to review and discuss the role of genetics in medically-relevant prediction. Germline genetics presages disease onset and therefore can contribute prognostic signals that augment laboratory tests and clinical features. As such, the impact of genetic-based predictive models on clinical decisions and therapy choice could be profound. However, given that (i) medical traits result from a complex interplay between genetic and environmental factors, (ii) the underlying genetic architectures for susceptibility to common diseases are not well-understood, and (iii) replicable susceptibility alleles, in combination, account for only a moderate amount of disease heritability, there are substantial challenges to constructing and implementing genetic risk prediction models with high utility. In spite of these challenges, concerted progress has continued in this area with an ongoing accumulation of studies that identify disease predisposing genotypes. Several statistical approaches with the aim of predicting disease have been published. Here we summarize the current state of disease susceptibility mapping and pharmacogenetics efforts for risk prediction, describe methods used to construct and evaluate genetic-based predictive models, and discuss applications. PMID:24917882

  14. Co-infection does not predict disease signs in Gopherus tortoises

    PubMed Central

    Gov, Ryan; Sandmeier, Franziska C.; Snyder, Sarah J.; Tracy, C. Richard

    2017-01-01

    In disease ecology, the host immune system interacts with environmental conditions and pathogen properties to affect the impact of disease on the host. Within the host, pathogens may interact to facilitate or inhibit each other's growth, and pathogens interact with different hosts differently. We investigated co-infection of two Mycoplasma and the association of infection with clinical signs of upper respiratory tract disease in four congeneric tortoise host species (Gopherus) in the United States to detect differences in infection risk and disease dynamics in these hosts. Mojave Desert tortoises had greater prevalence of Mycoplasma agassizii than Texas tortoises and gopher tortoises, while there were no differences in Mycoplasma testudineum prevalence among host species. In some host species, the presence of each pathogen influenced the infection intensity of the other; hence, these two mycoplasmas interact differently within different hosts, and our results may indicate facilitation of these bacteria. Neither infection nor co-infection was associated with clinical signs of disease, which tend to fluctuate across time. From M. agassizii DNA sequences, we detected no meaningful differentiation of haplotypes among hosts. Experimental inoculation studies and recurrent resampling of wild individuals could help to decipher the underlying mechanisms of disease dynamics in this system. PMID:29134096

  15. Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders?

    PubMed Central

    Luchowska-Kocot, Dorota; Kiełczykowska, Małgorzata; Musik, Irena; Kurzepa, Jacek

    2017-01-01

    Vitamin C (Vit C) is considered to be a vital antioxidant molecule in the brain. Intracellular Vit C helps maintain integrity and function of several processes in the central nervous system (CNS), including neuronal maturation and differentiation, myelin formation, synthesis of catecholamine, modulation of neurotransmission and antioxidant protection. The importance of Vit C for CNS function has been proven by the fact that targeted deletion of the sodium-vitamin C co-transporter in mice results in widespread cerebral hemorrhage and death on post-natal day one. Since neurological diseases are characterized by increased free radical generation and the highest concentrations of Vit C in the body are found in the brain and neuroendocrine tissues, it is suggested that Vit C may change the course of neurological diseases and display potential therapeutic roles. The aim of this review is to update the current state of knowledge of the role of vitamin C on neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis and amyotrophic sclerosis, as well as psychiatric disorders including depression, anxiety and schizophrenia. The particular attention is attributed to understanding of the mechanisms underlying possible therapeutic properties of ascorbic acid in the presented disorders. PMID:28654017

  16. Evaluation of the Centers for Disease Control and Prevention's chronic disease state-based epidemiology for public health program support (STEPPS) program.

    PubMed

    Frey, Catherine A; Remington, Patrick L; Lengerich, Eugene

    2003-01-01

    To identify effective strategies for improving epidemiology capacity in state chronic disease programs, staff epidemiologists and program directors from 25 states were interviewed using a structured questionnaire by phone or in person. Respondents reported three chief barriers to chronic disease epidemiology capacity: lack of institutional commitment and support for chronic disease epidemiology; lack of professional opportunities to engage with peers, colleagues, and scientists; and lack of trained epidemiology staff and resources to support chronic disease functions and activities. Epidemiology capacity in states would be improved by expanding the role and scope of staff placement programs; assisting states in establishing formal collaborations with academic institutions; and providing technical assistance to staff currently employed in states through training, consultation, and networking.

  17. Association between obesity and periodontal disease. A systematic review of epidemiological studies and controlled clinical trials

    PubMed Central

    Martinez-Herrera, Mayte; Silvestre-Rangil, Javier

    2017-01-01

    Background Obesity is a very prevalent chronic disease worldwide and has been suggested to increase susceptibility of periodontitis. The aim of this paper was to provide a systematic review of the association between obesity and periodontal disease, and to determine the possible mechanisms underlying in this relationship. Material and Methods A literature search was carried out in the databases PubMed-Medline and Embase. Controlled clinical trials and observational studies identifying periodontal and body composition parameters were selected. Each article was subjected to data extraction and quality assessment. Results A total of 284 articles were identified, of which 64 were preselected and 28 were finally included in the review. All the studies described an association between obesity and periodontal disease, except two articles that reported no such association. Obesity is characterized by a chronic subclinical inflammation that could exacerbate other chronic inflammatory disorders like as periodontitis. Conclusions The association between obesity and periodontitis was consistent with a compelling pattern of increased risk of periodontitis in overweight or obese individuals. Although the underlying pathophysiological mechanism remains unclear, it has been pointed out that the development of insulin resistance as a consequence of a chronic inflammatory state and oxidative stress could be implicated in the association between obesity and periodontitis. Further prospective longitudinal studies are needed to define the magnitude of this association and to elucidate the causal biological mechanisms. Key words:Periodontal disease, periodontitis, periodontal infection, obesity, abdominal obesity. PMID:29053651

  18. State-level minimum wage and heart disease death rates in the United States, 1980-2015: A novel application of marginal structural modeling.

    PubMed

    Van Dyke, Miriam E; Komro, Kelli A; Shah, Monica P; Livingston, Melvin D; Kramer, Michael R

    2018-07-01

    Despite substantial declines since the 1960's, heart disease remains the leading cause of death in the United States (US) and geographic disparities in heart disease mortality have grown. State-level socioeconomic factors might be important contributors to geographic differences in heart disease mortality. This study examined the association between state-level minimum wage increases above the federal minimum wage and heart disease death rates from 1980 to 2015 among 'working age' individuals aged 35-64 years in the US. Annual, inflation-adjusted state and federal minimum wage data were extracted from legal databases and annual state-level heart disease death rates were obtained from CDC Wonder. Although most minimum wage and health studies to date use conventional regression models, we employed marginal structural models to account for possible time-varying confounding. Quasi-experimental, marginal structural models accounting for state, year, and state × year fixed effects estimated the association between increases in the state-level minimum wage above the federal minimum wage and heart disease death rates. In models of 'working age' adults (35-64 years old), a $1 increase in the state-level minimum wage above the federal minimum wage was on average associated with ~6 fewer heart disease deaths per 100,000 (95% CI: -10.4, -1.99), or a state-level heart disease death rate that was 3.5% lower per year. In contrast, for older adults (65+ years old) a $1 increase was on average associated with a 1.1% lower state-level heart disease death rate per year (b = -28.9 per 100,000, 95% CI: -71.1, 13.3). State-level economic policies are important targets for population health research. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Mortality patterns among a Native American population in New York State.

    PubMed

    Michalek, A M; Mahoney, M C; Cummings, K M; Hanley, J; Snyder, R

    1989-10-01

    This study investigated patterns of mortality among a Native American tribe, the Seneca Nation of Indians (SNI). The names of 962 tribal members reported to have died in New York State between 1955 and the end of 1984 were identified through a review of tribal roll books maintained by the Seneca Nation. Positive matches were obtained for 796 (83%) of these individuals using New York State mortality files for the period under investigation. Standardized Proportionate Mortality Ratios (PMR) were computed for major causes of death based on cause-specific mortality patterns in the New York State population for each sex during the same time period. Significantly elevated risks of mortality were observed for all infectious diseases, tuberculosis, diabetes mellitus, cirrhosis, and accidents. Depressed mortality ratios were noted for deaths due to all cancers combined, and for cancers of the lung, pancreas, breast, and lymphatic/hematopoietic cancers. Changes in mortality risks over time were also observed.

  20. Sedentary lifestyle and state variation in coronary heart disease mortality.

    PubMed Central

    Yeager, K K; Anda, R F; Macera, C A; Donehoo, R S; Eaker, E D

    1995-01-01

    Using linear regression, the authors demonstrated a strong association between State-specific coronary heart disease mortality rates and State prevalence of sedentary lifestyle (r2 = 0.34; P = 0.0002) that remained significant after controlling for the prevalence of diagnosed hypertension, smoking, and overweight among the State's population. This ecologic analysis suggests that sedentary lifestyle may explain State variation in coronary heart disease mortality and reinforces the need to include physical activity promotion as a part of programs in the States to prevent heart disease. PMID:7838933

  1. Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells.

    PubMed

    Pournasr, Behshad; Duncan, Stephen A

    2017-11-01

    Inborn errors of hepatic metabolism are because of deficiencies commonly within a single enzyme as a consequence of heritable mutations in the genome. Individually such diseases are rare, but collectively they are common. Advances in genome-wide association studies and DNA sequencing have helped researchers identify the underlying genetic basis of such diseases. Unfortunately, cellular and animal models that accurately recapitulate these inborn errors of hepatic metabolism in the laboratory have been lacking. Recently, investigators have exploited molecular techniques to generate induced pluripotent stem cells from patients' somatic cells. Induced pluripotent stem cells can differentiate into a wide variety of cell types, including hepatocytes, thereby offering an innovative approach to unravel the mechanisms underlying inborn errors of hepatic metabolism. Moreover, such cell models could potentially provide a platform for the discovery of therapeutics. In this mini-review, we present a brief overview of the state-of-the-art in using pluripotent stem cells for such studies. © 2017 American Heart Association, Inc.

  2. Asthma Management in Sickle Cell Disease

    PubMed Central

    Morris, Claudia R.

    2013-01-01

    Asthma is a common comorbid factor in sickle cell disease (SCD). However, the incidence of asthma in SCD is much higher than expected compared to rates in the general population. Whether “asthma” in SCD is purely related to genetic and environmental factors or rather is the consequence of the underlying hemolytic and inflammatory state is a topic of recent debate. Regardless of the etiology, hypoxemia induced by bronchoconstriction and inflammation associated with asthma exacerbations will contribute to a cycle of sickling and subsequent complications of SCD. Recent studies confirm that asthma predisposes to complications of SCD such as pain crises, acute chest syndrome, and stroke and is associated with increased mortality. Early recognition and aggressive standard of care management of asthma may prevent serious pulmonary complications and reduce mortality. However, data regarding the management of asthma in SCD is very limited. Clinical trials are needed to evaluate the effectiveness of current asthma therapy in patients with SCD and coincident asthma, while mechanistic studies are needed to delineate the underlying pathophysiology. PMID:24324967

  3. Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons.

    PubMed

    Rodriguez-Rodriguez, Patricia; Sandebring-Matton, Anna; Merino-Serrais, Paula; Parrado-Fernandez, Cristina; Rabano, Alberto; Winblad, Bengt; Ávila, Jesús; Ferrer, Isidre; Cedazo-Minguez, Angel

    2017-12-01

    Insulin signalling deficiencies and insulin resistance have been directly linked to the progression of neurodegenerative disorders like Alzheimer's disease. However, to date little is known about the underlying molecular mechanisms or insulin state and distribution in the brain under pathological conditions. Here, we report that insulin is accumulated and retained as oligomers in hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of the most prevalent human tauopathies. The intraneuronal accumulation of insulin is directly dependent on tau hyperphosphorylation, and follows the tauopathy progression. Furthermore, cells accumulating insulin show signs of insulin resistance and decreased insulin receptor levels. These results suggest that insulin retention in hyperphosphorylated tau-bearing neurons is a causative factor for the insulin resistance observed in tauopathies, and describe a novel neuropathological concept with important therapeutic implications. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. An overview of Compassionate Use Programs in the European Union member states.

    PubMed

    Balasubramanian, Gayathri; Morampudi, Suman; Chhabra, Pankdeep; Gowda, Arun; Zomorodi, Behsad

    2016-11-01

    The past decade witnessed rapid development of novel drugs and therapeutic biological agents. The marketing authorization for novel therapies is often time consuming and distressing for patients. Earlier clinical trials were the only way to access new drugs under development. However, not every patient meets the enrolment criteria, and participation is difficult for patients with life-threatening, long-lasting or seriously debilitating diseases like rare diseases. Early access programs like "Compassionate Use Program (CUP)" have generated alternative channels for such patients. The European Medical Agency provides regulations and recommendations for compassionate use, upon which every European Union (EU) member state has developed its own rules and regulations. Despite previous reviews and studies, the available information is limited and gaps exist. This literature review explores CUP in 28 EU member states. Data was collected through literature review and use of country-specific search terms from the healthcare domain. Data sources were not limited to databases and articles published in journals, but also included grey literature. The results implied that CUP was present in 20 EU member states (71%). Of 28 EU states, 18 (∼64%) had nationalized regulations and processes were well-defined. Overall, this review identified CUP and its current status and legislation in 28 EU member states. The established legislation for CUP in the EU member states suggest their willingness to adopt processes that facilitate earlier and better access to new medicines. Further research and periodic reviews are warranted to understand the contemporary and future regulatory trends in early access programs.

  5. Molecular dynamics simulations of human E3 ubiquitin ligase Parkin

    PubMed Central

    Qiu, Shi; Zhu, Shun; Xu, Shan; Han, Yanyan; Liu, Wen; Zuo, Ji

    2017-01-01

    Human E3 ubiquitin protein ligase parkin (Parkin) mediates mitophagy to maintain mitochondrial homeostasis. Parkin mutations are common genetic causes of early onset familial Parkinson's disease. The molecular mechanism of Parkin activation has been widely studied with emerging evidence suggesting an essential role of the phosphorylated (phospho)-ubiquitin interaction. However, the underlying mechanism of the phospho-ubiquitin interaction remains elusive. In the present study, replica exchange molecular dynamics simulations were performed to examine the conformational dynamics of Parkin in monomer and phospho-ubiquitin-bound states. In the Parkin monomer state, high structural flexibilities were observed in the majority of regions of Parkin particularly in the loop domain between the ubiquitin-like (UBL) and really interesting new gene (RING)0 domain. Binding of phospho-ubiquitin stabilizes the RING1/RING in between RING interface but destabilizes the RING1-UBL interface. Furthermore, using steered molecular dynamics simulations of Parkin mutations, it was demonstrated that salt bridge interactions contribute significantly to the interdomain interactions between the RING1 and UBL domain. Taken together, the results of the present study revealed the conformational dynamics of human full-length Parkin in monomer and phospho-ubiquitin-bound states, providing insights into designing potential therapeutics against Parkinson's disease. PMID:28765939

  6. Are Cancer Registries Unconstitutional?

    PubMed Central

    McLaughlin, Robert H; Clarke, Christina A; Crawley, LaVera M; Glaser, Sally L

    2010-01-01

    Population-based cancer registration, mandated throughout the United States, is central to quantifying the breadth and impact of cancer. It facilitates research to learn what causes cancer to develop and, in many cases, lead to death. However, as concerns about privacy increase, cancer registration has come under question. Recently, its constitutionality was challenged on the basis of 1) the vagueness of statutory aims to pursue public health versus the individual privacy interests of cancer patients, and 2) the alleged indignity of one's individual medical information being transmitted to government authorities. Examining cancer registry statutes in states covered by the US National Cancer Institute's SEER Program and the US Centers for Disease Control and Prevention's National Program of Cancer Registries, we found that cancer registration laws do state specific public health benefits, and offer reasonable limits and safeguards on the government's possession of private medical information. Thus, we argue that cancer registration would survive constitutional review, is compatible with the civil liberties protected by privacy rights in the U.S., satisfies the conditions that justify public health expenditures, and serves human rights to enjoy the highest attainable standards of health, the advances of science, and the benefits of government efforts to prevent and control disease. PMID:20199835

  7. Peripheral blood gene expression profiles in metabolic syndrome, coronary artery disease and type 2 diabetes.

    PubMed

    Grayson, B L; Wang, L; Aune, T M

    2011-07-01

    To determine if individuals with metabolic disorders possess unique gene expression profiles, we compared transcript levels in peripheral blood from patients with coronary artery disease (CAD), type 2 diabetes (T2D) and their precursor state, metabolic syndrome to those of control (CTRL) subjects and subjects with rheumatoid arthritis (RA). The gene expression profile of each metabolic state was distinguishable from CTRLs and correlated with other metabolic states more than with RA. Of note, subjects in the metabolic cohorts overexpressed gene sets that participate in the innate immune response. Genes involved in activation of the pro-inflammatory transcription factor, NF-κB, were overexpressed in CAD whereas genes differentially expressed in T2D have key roles in T-cell activation and signaling. Reverse transcriptase PCR validation confirmed microarray results. Furthermore, several genes differentially expressed in human metabolic disorders have been previously shown to participate in inflammatory responses in murine models of obesity and T2D. Taken together, these data demonstrate that peripheral blood from individuals with metabolic disorders display overlapping and non-overlapping patterns of gene expression indicative of unique, underlying immune processes.

  8. Surveillance for Waterborne Disease Outbreaks Associated with Drinking Water — United States 2011-2012

    EPA Science Inventory

    Advances in water management and sanitation have reduced waterborne disease in the United States, although outbreaks continue to occur. Public health agencies in the U.S. states and territories* report information on waterborne disease outbreaks to the CDC Waterborne Disease and ...

  9. Cell mechanics as a marker for diseases: Biomedical applications of AFM

    NASA Astrophysics Data System (ADS)

    Rianna, Carmela; Radmacher, Manfred

    2016-08-01

    Many diseases are related to changes in cell mechanics. Atomic Force Microscopy (AFM) is one of the most suitable techniques allowing the investigation of both topography and mechanical properties of adherent cells with high spatial resolution under physiological conditions. Over the years the use of this technique in medical and clinical applications has largely increased, resulting in the notion of cell mechanics as a biomarker to discriminate between different physiological and pathological states of cells. Cell mechanics has proven to be a biophysical fingerprint able discerning between cell phenotypes, unraveling processes in aging or diseases, or even detecting and diagnosing cellular pathologies. We will review in this report some of the works on cell mechanics investigated by AFM with clinical and medical relevance in order to clarify the state of research in this field and to highlight the role of cell mechanics in the study of pathologies, focusing on cancer, blood and cardiovascular diseases. At the request of all authors of the paper, and with the agreement of the Proceedings Editor, an updated version of this article was published on 26 September 2016. The original version supplied to AIP Publishing contained blurred figures introduced during the PDF conversion process. Moreover, Equations (5), (6), and (7) were not correctly cited in the text. These errors have been corrected in the updated and republished article.

  10. Burden of Outdoor Air Pollution in Kerala, India—A First Health Risk Assessment at State Level

    PubMed Central

    Tobollik, Myriam; Razum, Oliver; Wintermeyer, Dirk; Plass, Dietrich

    2015-01-01

    Ambient air pollution causes a considerable disease burden, particularly in South Asia. The objective of the study is to test the feasibility of applying the environmental burden of disease method at state level in India and to quantify a first set of disease burden estimates due to ambient air pollution in Kerala. Particulate Matter (PM) was used as an indicator for ambient air pollution. The disease burden was quantified in Years of Life Lost (YLL) for the population (30 + years) living in urban areas of Kerala. Scenario analyses were performed to account for uncertainties in the input parameters. 6108 (confidence interval (95% CI): 4150–7791) of 81,636 total natural deaths can be attributed to PM, resulting in 96,359 (95% CI: 65,479–122,917) YLLs due to premature mortality (base case scenario, average for 2008–2011). Depending on the underlying assumptions the results vary between 69,582 and 377,195 YLLs. Around half of the total burden is related to cardiovascular deaths. Scenario analyses show that a decrease of 10% in PM concentrations would save 15,904 (95% CI: 11,090–19,806) life years. The results can be used to raise awareness about air quality standards at a local level and to support decision-making processes aiming at cleaner and healthier environments. PMID:26343701

  11. Does enteral nutrition affect clinical outcome? A systematic review of the randomized trials.

    PubMed

    Koretz, Ronald L; Avenell, Alison; Lipman, Timothy O; Braunschweig, Carol L; Milne, Anne C

    2007-02-01

    Both parenteral nutrition (PN) and enteral nutrition (EN) are widely advocated as adjunctive care in patients with various diseases. A systematic review of 82 randomized controlled trials (RCTs) of PN published in 2001 found little, if any, effect on mortality, morbidity, or duration of hospital stay; in some situations, PN increased infectious complication rates. The objective was to assess the effect of EN or volitional nutrition support (VNS) in individual disease states from available RCTs. We conducted a systematic review. RCTs comparing EN or VNS with untreated controls, or comparing EN with PN, were identified and separated according to the underlying disease state. Meta-analysis was performed when at least three RCTs provided data. The evidence from the RCTs was summarized into one of five grades. A or B, respectively, indicated the presence of strong or weak (low-quality RCTs) evidence supporting the use of the intervention. C indicated a lack of adequate evidence to make any decision about efficacy. D indicated that limited data could not support the intervention. E indicated either that strong data found no effect, or that either strong or weak data suggested that the intervention caused harm. RCTs could include either hospitalized or nonhospitalized patients. The EN or VNS had to be provided as part of a treatment plan for an underlying disease process. The RCT had to compare recipients of either EN or VNS with controls not receiving any type of artificial nutrition or had to compare recipients of EN with recipients of PN. These were mortality, morbidity (disease specific), duration of hospitalization, cost, or interventional complications. SUMMARY OF GRADING: A: No indication was identified. B: EN or VNS in the perioperative patient or in patients with chronic liver disease; EN in critically ill patients or low birth weight infants (trophic feeding); VNS in malnourished geriatric patients. (The low-quality trials found a significant difference in survival favoring the VNS recipients in the malnourished geriatric patient trials; two high-quality trials found nonsignificant differences that favored VNS as well.) C: EN or VNS in liver transplantation, cystic fibrosis, renal failure, pediatric conditions other than low birth weight infants, well-nourished geriatric patients, nonstroke neurologic conditions, AIDS; EN in acute pancreatitis, chronic obstructive pulmonary disease, nonmalnourished geriatric patients; VNS in inflammatory bowel disease, arthritis, cardiac disease, pregnancy, allergic patients, preoperative bowel preparation. D: EN or VNS in patients receiving nonsurgical cancer treatment or in patients with hip fractures; EN in patients with inflammatory bowel disease; VNS in patients with chronic obstructive pulmonary disease. E: EN in the first week in dysphagic, or VNS at any time in nondysphagic, stroke patients who are not malnourished; dysphagia persisting for weeks will presumably ultimately require EN. There is strong evidence for not using EN in the first week in dysphagic, and not using VNS at all in nondysphagic, stroke patients who are not malnourished. There is reasonable evidence for using VNS in malnourished geriatric patients. The recommendations to consider EN/VNS in perioperative/liver/critically ill/low birth weight patients are limited by the low quality of the RCTs. No evidence could be identified to justify the use of EN/VNS in other disease states.

  12. Validity of cardiovascular risk prediction models in Latin America and among Hispanics in the United States of America: a systematic review.

    PubMed

    Cortes-Bergoderi, Mery; Thomas, Randal J; Albuquerque, Felipe N; Batsis, John A; Burdiat, Gerard; Perez-Terzic, Carmen; Trejo-Gutierrez, Jorge; Lopez-Jimenez, Francisco

    2012-08-01

    To assess the use and validity of prediction models to estimate the risk of cardiovascular disease (CVD) in Latin America and among Hispanic populations in the United States of America. This was a systematic review of three databases: Ovid MEDLINE (1 January 1950-15 April 2010), LILACS (1 January 1988-15 April 2010), and EMBASE (1 January 1988-15 April 2010). MeSH search terms and domains were related to CVD, prediction rules, Latin America (including the Caribbean), and Hispanics in the United States. Database searches were supplemented by correspondence with experts in the field. A total of 1 655 abstracts were identified, of which five cohorts with a total of 13 142 subjects met inclusion criteria. A Mexican cohort showed that the predicted/observed event-rate ratio for coronary heart disease (CHD) according to the Framingham risk score (FRS) was 1.68 (95% CI, 1.26-2.11); incident myocardial infarction, 1.36 (95% CI, 0.90-1.83); and CHD death, 1.21 (95% CI, 0.43-2.00). In Ecuador, a prediction model for CVD and total deaths in hypertensive patients had an area under the curve (AUC) of 0.79 (95% CI, 0.72-0.86), while the World Health Organization method had an AUC of 0.74 (95% CI, 0.67-0.82). A study predicting mortality risk in people with Chagas' disease had an AUC of 0.81 (95% CI, 0.72-0.90). Among a United State s cohort that included Hispanics, FRS overestimated CVD risk for Hispanics with an AUC of 0.69. Another study in the United States that assessed FRS factors predicting CVD death among Mexican-Americans had an AUC of 0.78. The evidence regarding CVD risk prediction rules in Latin America or among Hispanics in the United States is modest at best. It is likely that the FRS overestimates CVD risk in Hispanics when not properly recalibrated.

  13. A review of infectious agents in polar bears (Ursus maritimus) and their long-term ecological relevance

    USGS Publications Warehouse

    Fagre, Anna C.; Patyk, Kelly A.; Nol, Pauline; Atwood, Todd C.; Hueffer, Karsten; Duncan, Colleen G.

    2015-01-01

    Disease was a listing criterion for the polar bear (Ursus maritimus) as threatened under the Endangered Species Act in 2008; it is therefore important to evaluate the current state of knowledge and identify any information gaps pertaining to diseases in polar bears. We conducted a systematic literature review focused on infectious agents and associated health impacts identified in polar bears. Overall, the majority of reports in free-ranging bears concerned serosurveys or fecal examinations with little to no information on associated health effects. In contrast, most reports documenting illness or pathology referenced captive animals and diseases caused by etiologic agents not representative of exposure opportunities in wild bears. As such, most of the available infectious disease literature has limited utility as a basis for development of future health assessment and management plans. Given that ecological change is a considerable risk facing polar bear populations, future work should focus on cumulative effects of multiple stressors that could impact polar bear population dynamics.

  14. A Review of Infectious Agents in Polar Bears (Ursus maritimus) and Their Long-Term Ecological Relevance.

    PubMed

    Fagre, Anna C; Patyk, Kelly A; Nol, Pauline; Atwood, Todd; Hueffer, Karsten; Duncan, Colleen

    2015-09-01

    Disease was a listing criterion for the polar bear (Ursus maritimus) as threatened under the Endangered Species Act in 2008; it is therefore important to evaluate the current state of knowledge and identify any information gaps pertaining to diseases in polar bears. We conducted a systematic literature review focused on infectious agents and associated health impacts identified in polar bears. Overall, the majority of reports in free-ranging bears concerned serosurveys or fecal examinations with little to no information on associated health effects. In contrast, most reports documenting illness or pathology referenced captive animals and diseases caused by etiologic agents not representative of exposure opportunities in wild bears. As such, most of the available infectious disease literature has limited utility as a basis for development of future health assessment and management plans. Given that ecological change is a considerable risk facing polar bear populations, future work should focus on cumulative effects of multiple stressors that could impact polar bear population dynamics.

  15. Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism.

    PubMed

    Skotte, Niels H; Andersen, Jens V; Santos, Alberto; Aldana, Blanca I; Willert, Cecilie W; Nørremølle, Anne; Waagepetersen, Helle S; Nielsen, Michael L

    2018-05-15

    Huntington's disease is a fatal neurodegenerative disease, where dysfunction and loss of striatal and cortical neurons are central to the pathogenesis of the disease. Here, we integrated quantitative studies to investigate the underlying mechanisms behind HD pathology in a systems-wide manner. To this end, we used state-of-the-art mass spectrometry to establish a spatial brain proteome from late-stage R6/2 mice and compared this with wild-type littermates. We observed altered expression of proteins in pathways related to energy metabolism, synapse function, and neurotransmitter homeostasis. To support these findings, metabolic 13 C labeling studies confirmed a compromised astrocytic metabolism and regulation of glutamate-GABA-glutamine cycling, resulting in impaired release of glutamine and GABA synthesis. In recent years, increasing attention has been focused on the role of astrocytes in HD, and our data support that therapeutic strategies to improve astrocytic glutamine homeostasis may help ameliorate symptoms in HD. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy.

    PubMed

    Vilchez, David; Ros, Susana; Cifuentes, Daniel; Pujadas, Lluís; Vallès, Jordi; García-Fojeda, Belén; Criado-García, Olga; Fernández-Sánchez, Elena; Medraño-Fernández, Iria; Domínguez, Jorge; García-Rocha, Mar; Soriano, Eduardo; Rodríguez de Córdoba, Santiago; Guinovart, Joan J

    2007-11-01

    Glycogen synthesis is normally absent in neurons. However, inclusion bodies resembling abnormal glycogen accumulate in several neurological diseases, particularly in progressive myoclonus epilepsy or Lafora disease. We show here that mouse neurons have the enzymatic machinery for synthesizing glycogen, but that it is suppressed by retention of muscle glycogen synthase (MGS) in the phosphorylated, inactive state. This suppression was further ensured by a complex of laforin and malin, which are the two proteins whose mutations cause Lafora disease. The laforin-malin complex caused proteasome-dependent degradation both of the adaptor protein targeting to glycogen, PTG, which brings protein phosphatase 1 to MGS for activation, and of MGS itself. Enforced expression of PTG led to glycogen deposition in neurons and caused apoptosis. Therefore, the malin-laforin complex ensures a blockade of neuronal glycogen synthesis even under intense glycogenic conditions. Here we explain the formation of polyglucosan inclusions in Lafora disease by demonstrating a crucial role for laforin and malin in glycogen synthesis.

  17. International Health Regulations in practice: Focus on yellow fever and poliomyelitis.

    PubMed

    Simons, H; Patel, D

    2016-10-02

    ASBTRACT The spread of infectious disease represents a global threat and therefore remains a priority on the international public health agenda. The International Health Regulations (IHR) (2005) came into effect in June 2007 and provide a legal framework to which the 196 member states of the World Health Assembly agree to abide. 1 These regulations include implementation of protective, control and response measures at points of entry to a country (i.e. land borders, sea and airports), and of notification measures, all of which aim to prevent or limit the spread of disease while minimising disruption to international trade. The World Health Organization can apply and enforce IHR (2005) to any disease considered to pose a significant threat to international public health. This short paper focuses on 2 diseases; yellow fever and poliomyelitis, both of which have the potential to spread internationally. It will discuss the measures applied under IHR (2005) to minimize the threat, and explore the implications for both travelers and travel health advisors.

  18. Disease-Associated Plasmacytoid Dendritic Cells

    PubMed Central

    Li, Shuang; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao

    2017-01-01

    Plasmacytoid dendritic cells (pDCs), also called natural interferon (IFN)-producing cells, represent a specialized cell type within the innate immune system. pDCs are specialized in sensing viral RNA and DNA by toll-like receptor-7 and -9 and have the ability to rapidly produce massive amounts of type 1 IFNs upon viral encounter. After producing type 1 IFNs, pDCs differentiate into professional antigen-presenting cells, which are capable of stimulating T cells of the adaptive immune system. Chronic activation of human pDCs by self-DNA or mitochondrial DNA contributes to the pathogenesis of systemic lupus erythematosis and IFN-related autoimmune diseases. Under steady-state conditions, pDCs play an important role in immune tolerance. In many types of human cancers, recruitment of pDCs to the tumor microenvironment contributes to the induction of immune tolerance. Here, we provide a systemic review of recent progress in studies on the role of pDCs in human diseases, including cancers and autoimmune/inflammatory diseases. PMID:29085361

  19. Dysthymia and Apathy: Diagnosis and Treatment

    PubMed Central

    Ishizaki, Junko; Mimura, Masaru

    2011-01-01

    Dysthymia is a depressive mood disorder characterized by chronic and persistent but mild depression. It is often difficult to be distinguished from major depression, specifically in its partially remitted state because “loss of interest” or “apathy” tends to prevail both in dysthymia, and remitted depression. Apathy may also occur in various psychiatric and neurological disorders, including schizophrenia, stroke, Parkinson's disease, progressive supranuclear palsy, Huntington's disease, and dementias such as Alzheimer's disease, vascular dementia, and frontotemporal dementia. It is symptomatologically important that apathy is related to, but different from, major depression from the viewpoint of its causes and treatment. Antidepressants, especially noradrenergic agents, are useful for depression-related apathy. However, selective serotonin reuptake inhibitors (SSRIs) may be less effective for apathy in depressed elderly patients and have even been reported to worsen apathy. Dopaminergic agonists seem to be effective for apathy. Acetylcholine esterase inhibitors, methylphenidate, atypical antipsychotics, nicergoline, and cilostazol are another choice. Medication choice should be determined according to the background and underlying etiology of the targeting disease. PMID:21747995

  20. Preventing Emerging Infectious Diseases: A Strategy for the 21st Century. Overview of the Updated CDC plan.

    PubMed

    1998-09-11

    Societal, technological, and environmental factors continue to have a dramatic effect on infectious diseases worldwide, facilitating the emergence of new diseases and the reemergence of old ones, sometimes in drug-resistant forms. Modern demographic and ecologic conditions that favor the spread of infectious diseases include rapid population growth; increasing poverty and urban migration; more frequent movement across international boundaries by tourists, workers, immigrants, and refugees; alterations in the habitats of animals and arthropods that transmit disease; increasing numbers of persons with impaired host defenses; and changes in the way that food is processed and distributed. Several recent health events underscore the need for a public health system ready to address whatever disease problems that might arise. For example, in 1997, an avian strain of influenza that had never before infected humans began to kill previously healthy persons in Hong Kong, and strains of Sta phylococcus aureus with diminished susceptibility to the antibiotic vancomycin were reported in Japan and the United States. In addition, researchers recently discovered that a strain of the virus that causes acquired immunodeficiency syndrome (AIDS) had been infecting humans for at least 20 years before AIDS emerged as a worldwide epidemic. Preventing Emerging Infectious Diseases: A Strategy for the 21st Century describes CDC's plan to combat today's infectious diseases and prevent those of tomorrow. It represents the second phase of the effort launched in 1994 with the publication of CDC's Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States. This overview of the updated plan outlines specific objectives under four major goals: a) surveillance and response, b) applied research, c) infrastructure and training, and d) prevention and control. Achieving these objectives will enhance understanding of infectious diseases and bolster their detection, control, and prevention. The plan also targets nine categories of problems that cause human suffering and place a burden on society. The aim of this plan is to build a stronger, more flexible U.S. public health system that is well-prepared to respond to known disease problems, as well as to address the unexpected, whether it be an influenza pandemic, a disease caused by an unknown organism, or a bioterrorist attack. The implementation of this plan will require the dedicated efforts of many partners, including state and local health departments, other federal agencies, professional societies, universities, research institutes, health-care providers and organizations, the World Health Organization, and many other domestic and international organizations and groups.

  1. Transmission models and management of lymphatic filariasis elimination.

    PubMed

    Michael, Edwin; Gambhir, Manoj

    2010-01-01

    The planning and evaluation of parasitic control programmes are complicated by the many interacting population dynamic and programmatic factors that determine infection trends under different control options. A key need is quantification about the status of the parasite system state at any one given timepoint and the dynamic change brought upon that state as an intervention program proceeds. Here, we focus on the control and elimination of the vector-borne disease, lymphatic filariasis, to show how mathematical models of parasite transmission can provide a quantitative framework for aiding the design of parasite elimination and monitoring programs by their ability to support (1) conducting rational analysis and definition of endpoints for different programmatic aims or objectives, including transmission endpoints for disease elimination, (2) undertaking strategic analysis to aid the optimal design of intervention programs to meet set endpoints under different endemic settings and (3) providing support for performing informed evaluations of ongoing programs, including aiding the formation of timely adaptive management strategies to correct for any observed deficiencies in program effectiveness. The results also highlight how the use of a model-based framework will be critical to addressing the impacts of ecological complexities, heterogeneities and uncertainties on effective parasite management and thereby guiding the development of strategies to resolve and overcome such real-world complexities. In particular, we underscore how this approach can provide a link between ecological science and policy by revealing novel tools and measures to appraise and enhance the biological controllability or eradicability of parasitic diseases. We conclude by emphasizing an urgent need to develop and apply flexible adaptive management frameworks informed by mathematical models that are based on learning and reducing uncertainty using monitoring data, apply phased or sequential decision-making to address extant uncertainty and focus on developing ecologically resilient management strategies, in ongoing efforts to control or eliminate filariasis and other parasitic diseases in resource-poor communities.

  2. Quarantine, exports and animal disease in Australia 1901-2010.

    PubMed

    Turner, Aj

    2011-09-01

    The Constitution forming the Australian Commonwealth Government on 1 January 1901 provided that animal and animal products imported into and exported from Australia would be under the authority of the national government. By mutual agreement, the Quarantine Act 1908 provided for the states to continue the delivery of services under contract until 1995 when the Commonwealth took back full responsibility for quarantine services. In the 1940s, 50s and 60s there were world pandemics of livestock diseases and Australia ceased the import of many species. By the 1970s, the livestock industries sought relaxation of import restrictions to gain access to diversified genetic stock. By the use of new technologies, many species can now be imported into Australia through tight importation protocols. With the advent of the World Trade Organization and implementation of the Sanitary Phytosanitary Agreement, Australia has developed a risk-based framework to support the development of import conditions for animals and animal products. Australia's 'Acceptable Level of Protection' has been set to provide a low likelihood of disease entry. Being an island continent, Australia can apply strong controls over imports and exports of all commodities and relatively few outbreaks of exotic animal diseases have occurred by breach of quarantine, but the outbreaks of rinderpest in 1923 and equine influenza in 2007 were notable exceptions. © 2011 The Author. Australian Veterinary Journal © 2011 Australian Veterinary Association.

  3. Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease.

    PubMed

    Abautret-Daly, Áine; Dempsey, Elaine; Parra-Blanco, Adolfo; Medina, Carlos; Harkin, Andrew

    2017-03-08

    Introduction Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterised by inflammation of the gastrointestinal tract. There is a growing consensus that IBD is associated with anxiety- and depression-related symptoms. Psychological symptoms appear to be more prevalent during active disease states with no difference in prevalence between Crohn's disease and ulcerative colitis. Behavioural disturbances including anxiety- and depression-like symptoms have also been observed in animal models of IBD. The likely mechanisms underlying the association are discussed with particular reference to communication between the gut and brain. The close bidirectional relationship known as the gut-brain axis includes neural, hormonal and immune communication links. Evidence is provided for a number of interacting factors including activation of the inflammatory response system in the brain, the hypothalamic-pituitary-adrenal axis, and brain areas implicated in altered behaviours, changes in blood brain barrier integrity, and an emerging role for gut microbiota and response to probiotics in IBD. Discussion The impact of psychological stress in models of IBD remains somewhat conflicted, however, it is weighted in favour of stress or early stressful life events as risk factors in the development of IBD, stress-induced exacerbation of inflammation and relapse. It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.

  4. Diet and microbiota in inflammatory bowel disease: The gut in disharmony.

    PubMed

    Rapozo, Davy C M; Bernardazzi, Claudio; de Souza, Heitor Siffert Pereira

    2017-03-28

    Bacterial colonization of the gut shapes both the local and the systemic immune response and is implicated in the modulation of immunity in both healthy and disease states. Recently, quantitative and qualitative changes in the composition of the gut microbiota have been detected in Crohn's disease and ulcerative colitis, reinforcing the hypothesis of dysbiosis as a relevant mechanism underlying inflammatory bowel disease (IBD) pathogenesis. Humans and microbes have co-existed and co-evolved for a long time in a mutually beneficial symbiotic association essential for maintaining homeostasis. However, the microbiome is dynamic, changing with age and in response to environmental modifications. Among such environmental factors, food and alimentary habits, progressively altered in modern societies, appear to be critical modulators of the microbiota, contributing to or co-participating in dysbiosis. In addition, food constituents such as micronutrients are important regulators of mucosal immunity, with direct or indirect effects on the gut microbiota. Moreover, food constituents have recently been shown to modulate epigenetic mechanisms, which can result in increased risk for the development and progression of IBD. Therefore, it is likely that a better understanding of the role of different food components in intestinal homeostasis and the resident microbiota will be essential for unravelling the complex molecular basis of the epigenetic, genetic and environment interactions underlying IBD pathogenesis as well as for offering dietary interventions with minimal side effects.

  5. Health Extension in New Mexico: An Academic Health Center and the Social Determinants of Disease

    PubMed Central

    Kaufman, Arthur; Powell, Wayne; Alfero, Charles; Pacheco, Mario; Silverblatt, Helene; Anastasoff, Juliana; Ronquillo, Francisco; Lucero, Ken; Corriveau, Erin; Vanleit, Betsy; Alverson, Dale; Scott, Amy

    2010-01-01

    The Agricultural Cooperative Extension Service model offers academic health centers methodologies for community engagement that can address the social determinants of disease. The University of New Mexico Health Sciences Center developed Health Extension Rural Offices (HEROs) as a vehicle for its model of health extension. Health extension agents are located in rural communities across the state and are supported by regional coordinators and the Office of the Vice President for Community Health at the Health Sciences Center. The role of agents is to work with different sectors of the community in identifying high-priority health needs and linking those needs with university resources in education, clinical service and research. Community needs, interventions, and outcomes are monitored by county health report cards. The Health Sciences Center is a large and varied resource, the breadth and accessibility of which are mostly unknown to communities. Community health needs vary, and agents are able to tap into an array of existing health center resources to address those needs. Agents serve a broader purpose beyond immediate, strictly medical needs by addressing underlying social determinants of disease, such as school retention, food insecurity, and local economic development. Developing local capacity to address local needs has become an overriding concern. Community-based health extension agents can effectively bridge those needs with academic health center resources and extend those resources to address the underlying social determinants of disease. PMID:20065282

  6. Diet and microbiota in inflammatory bowel disease: The gut in disharmony

    PubMed Central

    Rapozo, Davy C M; Bernardazzi, Claudio; de Souza, Heitor Siffert Pereira

    2017-01-01

    Bacterial colonization of the gut shapes both the local and the systemic immune response and is implicated in the modulation of immunity in both healthy and disease states. Recently, quantitative and qualitative changes in the composition of the gut microbiota have been detected in Crohn’s disease and ulcerative colitis, reinforcing the hypothesis of dysbiosis as a relevant mechanism underlying inflammatory bowel disease (IBD) pathogenesis. Humans and microbes have co-existed and co-evolved for a long time in a mutually beneficial symbiotic association essential for maintaining homeostasis. However, the microbiome is dynamic, changing with age and in response to environmental modifications. Among such environmental factors, food and alimentary habits, progressively altered in modern societies, appear to be critical modulators of the microbiota, contributing to or co-participating in dysbiosis. In addition, food constituents such as micronutrients are important regulators of mucosal immunity, with direct or indirect effects on the gut microbiota. Moreover, food constituents have recently been shown to modulate epigenetic mechanisms, which can result in increased risk for the development and progression of IBD. Therefore, it is likely that a better understanding of the role of different food components in intestinal homeostasis and the resident microbiota will be essential for unravelling the complex molecular basis of the epigenetic, genetic and environment interactions underlying IBD pathogenesis as well as for offering dietary interventions with minimal side effects. PMID:28405140

  7. Clinical outcomes of pneumocystis pneumonia from a tertiary care centre in Pakistan.

    PubMed

    Sarwar Zubairi, Ali Bin; Shahzad, Hira; Zafar, Afia

    2016-11-01

    To assess the predisposing immunocompromised states, administration of pneumocystis jirovecii pneumonia prophylaxis, the disease course and outcomes of patients with pneumocystis jirovecii pneumonia. The retrospective study was conducted at the Aga Khan University Hospital in Karachi. The medical records of patients diagnosed with pneumocystis jirovecii pneumonia from January 1995 to October 2015 were retrieved. Baseline characteristics, clinical course, treatment, and mortality rates were noted. SPSS 19 was used for data analysis. Of the 37 patients, 24(64.9%) were men and 13(35.1%) were women. The overall mean presenting age was 47.08±16.21 years (range: 19-83 years). Ten (27%) patients were positive for human immunodeficiency virus; 12(32.4%) had an underlying autoimmune disease; 3(8.1%) were transplant recipients; 10(27%) had an underlying malignancy, and 19(51.3%) were on long-term corticosteroid therapy. Only 2(5.4%) patients had received pneumocystis jirovecii pneumonia prophylaxis with trimethoprim-sulfamethoxazole. Moreover, 8(21.6%) patients required intensive care unit admission with a mean stay of 2.03±4.91 days (range: 1-22 days).The overall mortality rate was 7(18.9%). Pneumonia due to pneumocystis jirovecii was found to be a life-threatening disease in the immunocompromised population. The high mortality burden and resource intensive management of the disease emphasizes the need for PCP prophylaxis in immunosuppressed individuals.

  8. The heterogeneity of schizophrenia in disease states.

    PubMed

    Mohr, Penny E; Cheng, C Michael; Claxton, Karl; Conley, Robert R; Feldman, Jacob J; Hargreaves, William A; Lehman, Anthony F; Lenert, Leslie A; Mahmoud, Ramy; Marder, Stephen R; Neumann, Peter J

    2004-11-01

    Some of the contents of this paper have been previously presented at the 16th Annual Meeting of the International Society for Technology Assessment in Health Care June 20, 2000 in the Hague, Netherlands and at the 21st Annual Meeting of the Society for Medical Decision Making as a poster on October 3, 1999 in Reno, NV. Studies of schizophrenia treatment often oversimplify the array of health outcomes among patients. Our objective was to derive a set of disease states for schizophrenia using the Positive and Negative Symptom Assessment Scale (PANSS) that captured the heterogeneity of symptom responses. Using data from a 1-year clinical trial that collected PANSS scores and costs on schizophrenic patients (N=663), we conducted a k-means cluster analyses on PANSS scores for items in five factor domains. Results of the cluster analysis were compared with a conceptual framework of disease states developed by an expert panel. Final disease states were defined by combining our conceptual framework with the empirical results. We tested its utility by examining the influence of disease state on treatment costs and prognosis. Analyses led to an eight-state framework with varying levels of positive, negative, and cognitive impairment. The extent of hostile/aggressive symptoms and mood disorders correlated with severity of disease states. Direct treatment costs for schizophrenia vary significantly across disease states (F=27.47, df=7, p<0.0001), and disease state at baseline was among the most important predictors of treatment outcomes. The disease states we describe offer a useful paradigm for understanding the links between symptom profiles and outcomes.

  9. Cognitive states influence dopamine-driven aberrant learning in Parkinson’s disease

    PubMed Central

    Cavanagh, James F.; Mueller, Andrea A.; Brown, Darin R.; Janowich, Jacqueline R.; Story-Remer, Jacqueline H.; Wegele, Ashley; Richardson, Sarah Pirio

    2017-01-01

    Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson’s patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson’s patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson’s patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson’s patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N=28 Parkinson’s disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson’s patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON vs. OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to quantify phenotypic expressions of idiosyncratic disease progression. PMID:28384481

  10. Cognitive states influence dopamine-driven aberrant learning in Parkinson's disease.

    PubMed

    Cavanagh, James F; Mueller, Andrea A; Brown, Darin R; Janowich, Jacqueline R; Story-Remer, Jacqueline H; Wegele, Ashley; Richardson, Sarah Pirio

    2017-05-01

    Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson's patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson's patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson's patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson's patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N = 28 Parkinson's disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson's patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON versus OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to quantify phenotypic expressions of idiosyncratic disease progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 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.

  12. Early life nutritional programming of health and disease in The Gambia.

    PubMed

    Moore, S E

    2016-04-01

    Exposures during the early life (periconceptional, prenatal and early postnatal) period are increasingly recognized as playing an important role in the aetiology of chronic non-communicable diseases (NCD), including coronary heart disease, stroke, hypertension, Type 2 diabetes and osteoporosis. The 'Developmental Origins of Health and Disease' (DOHaD) hypothesis states that these disorders originate through unbalanced nutrition early in life and risk is highest when there is a 'mismatch' between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in countries where an excess of infants are born with low birth weight and where there is a rapid transition to nutritional adequacy or excess in adulthood. Here, I will review data from work conducted in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomized controlled trials of nutritional supplementation in pregnancy and the 'experiment of nature' that seasonality in this region provides, we have investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs.

  13. Genome-Wide Association of Rice Blast Disease Resistance and Yield-Related Components of Rice.

    PubMed

    Wang, Xueyan; Jia, Melissa H; Ghai, Pooja; Lee, Fleet N; Jia, Yulin

    2015-12-01

    Robust disease resistance may require an expenditure of energy that may limit crop yield potential. In the present study, a subset of a United States Department of Agriculture rice core collection consisting of 151 accessions was selected using a major blast resistance (R) gene, Pi-ta, marker and was genotyped with 156 simple sequence repeat (SSR) markers. Disease reactions to Magnaporthe oryzae, the causal agent of rice blast disease, were evaluated under greenhouse and field conditions, and heading date, plant height, paddy and brown seed weight in two field environments were analyzed, using an association mapping approach. A total of 21 SSR markers distributed among rice chromosomes 2 to 12 were associated with blast resistance, and 16 SSR markers were associated with seed weight, heading date, and plant height. Most noticeably, shorter plants were significantly correlated with resistance to blast, rice genomes with Pi-ta were associated with lighter seed weights, and the susceptible alleles of RM171 and RM6544 were associated with heavier seed weight. These findings unraveled a complex relationship between disease resistance and yield-related components.

  14. Proving personal use: the admissibility of evidence negating intent to distribute marijuana.

    PubMed

    Mayer, Stephen

    2015-05-01

    Against the backdrop of escalating state efforts to decriminalize marijuana, U.S. Attorneys' Offices continue to bring drug-trafficking prosecutions against defendants carrying small amounts of marijuana that are permitted under state law. Federal district courts have repeatedly barred defendants from introducing evidence that they possessed this marijuana for their own personal use. This Note argues that district courts should not exclude three increasingly common kinds of "personal use evidence" under Federal Rules of Evidence 402 and 403 when that evidence is offered to negate intent to distribute marijuana. Three types of personal use evidence are discussed in this Note: (1) a defendant's possession of a state-issued medical marijuana license, (2) evidence that a state has legalized possession of marijuana for recreational purposes, and (3) evidence that a defendant suffers from a disease that marijuana arguably treats. Part I examines each of these three categories of personal use evidence and contends that district courts are likely to confront disputes over such evidence with increasing frequency. Part II analyzes objections to the admissibility of personal use evidence on direct examination, focusing primarily on Rules 402 and 403. Part III responds to those objections and argues that the evidence is probative of intent to distribute in federal marijuana-trafficking prosecutions.

  15. Change rates and prevalence of a dichotomous variable: simulations and applications.

    PubMed

    Brinks, Ralph; Landwehr, Sandra

    2015-01-01

    A common modelling approach in public health and epidemiology divides the population under study into compartments containing persons that share the same status. Here we consider a three-state model with the compartments: A, B and Dead. States A and B may be the states of any dichotomous variable, for example, Healthy and Ill, respectively. The transitions between the states are described by change rates, which depend on calendar time and on age. So far, a rigorous mathematical calculation of the prevalence of property B has been difficult, which has limited the use of the model in epidemiology and public health. We develop a partial differential equation (PDE) that simplifies the use of the three-state model. To demonstrate the validity of the PDE, it is applied to two simulation studies, one about a hypothetical chronic disease and one about dementia in Germany. In two further applications, the PDE may provide insights into smoking behaviour of males in Germany and the knowledge about the ovulatory cycle in Egyptian women.

  16. Evaluation and Management of Refractory Acne Vulgaris in Adolescent and Adult Men.

    PubMed

    McCarty, Morgan

    2016-04-01

    Acne vulgaris alters the normal skin physiology, impairing stratum corneum and transepidermal water loss. A male's normal skin physiologic state is different than a female's and may have implications when choosing treatment when the skin is altered in a disease state. Transepidermal water loss, pH, and sebum production are different between the sexes. Several underlying conditions present in male acne patients at several ages that may require a more in-depth evaluation. As knowledge of the pathogenesis of acne expands, the differences in skin physiology between the sexes may alter the manner in which male patients with acne medications are approached. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Combination benefit of cognitive rehabilitation plus donepezil for Alzheimer's disease patients.

    PubMed

    Matsuzono, Kosuke; Hishikawa, Nozomi; Takao, Yoshiki; Wakutani, Yosuke; Yamashita, Toru; Deguchi, Kentaro; Abe, Koji

    2016-02-01

    Alzheimer's disease (AD) is one of the most important diseases in aging society, and non-drug therapy might be an alternative therapeutic approach. Thus, we evaluated the add-on effect of cognitive rehabilitation on AD patients under donepezil treatment. We retrospectively analyzed 55 AD patients with a Mini-Mental State Examination score of 15-25, dividing them into two groups depending on whether they were receiving ambulatory cognitive rehabilitation (group D + R, n = 32) or not (group D, n = 23) in Kurashiki Heisei Hospital over 1 year. The present cognitive rehabilitation included physical therapy, occupational therapy and speech therapy for 1-2 h once or twice a week. Between group D and group D + R, there was no significant difference in baseline data, such as age, Mini-Mental State Examination score, periventricular hyperintensity on magnetic resonance imaging, deep white matter hyperintensity on magnetic resonance imaging or donepezil dose (4.1 mg/day). At 1 year later, however, the Mini-Mental State Examination score improved only in group D + R from 21.7 to 24.0 (**P < 0.001), whereas that of group D remained at 21.5 with both groups of donepezil 5.0 mg/day. The combination of cognitive rehabilitation plus a choline esterase inhibitor donepezil showed a better effect for the cognitive function of AD patients than drug only therapy at 1 year. © 2015 Japan Geriatrics Society.

  18. Secondary osteoporosis.

    PubMed

    Boyle, I T

    1993-10-01

    Osteoporosis with attendant increased fracture risk is a common complication of many other diseases. Indeed, almost all chronic diseases make some impact on life-style, usually by restricting physical activity and hence reducing the anabolic effect of exercise and gravitational strains on the skeleton. Restricted appetite and modified gastrointestinal tract function is another commonplace finding that has an impact on bone nutrition and synthesis, as on other systems. Sex hormone status is of particular importance for the maintenance of the normal skeleton, and the postmenopausal woman is at particular risk for most causes of secondary osteoporosis. In dealing with secondary osteoporosis in the hypo-oestrogenic woman, the question of giving hormone replacement therapy in addition to other disease-specific therapy should always be considered, as, for example, in a young amenorrhoeic woman with Crohn's disease. Similarly, in hypogonadal men the administration of testosterone is useful for bone conservation. The wider availability of bone densitometry ought to make us more aware of the presence of osteoporosis in the many disease states discussed above. This is particularly important as the life span of such patients is now increased by improved management of the underlying disease process in many instances. Even in steroid-induced osteoporosis--one of the commonest and most severe forms of osteoporosis--we now have some effective therapy in the form of the bisphosphonates and other anti-bone-resorbing drug classes. The possibility of prophylaxis against secondary osteoporosis has therefore become a possibility, although the very long-term effects of such drug regimens are still unknown. In some situations, such as thyrotoxicosis, Cushing's syndrome and immobilization, spontaneous resolution of at least part of the osteoporosis is possible after cure of the underlying problem. The shorter the existence of the basic problem, the more successful the restoration of the skeleton appears to be. A useful credo for clinicians with respect to secondary osteoporosis is: to think of it; to use specific therapy for the underlying disease; to reduce or remove completely any relevant drug or toxic material; to optimize physical activity and general nutrition; to treat hypogonadism if present and feasible; and to consider the use of specific anti-bone-resorbing or other bone active drugs.

  19. Positron emission tomography (PET) advances in neurological applications

    NASA Astrophysics Data System (ADS)

    Sossi, V.

    2003-09-01

    Positron Emission Tomography (PET) is a functional imaging modality used in brain research to map in vivo neurotransmitter and receptor activity and to investigate glucose utilization or blood flow patterns both in healthy and disease states. Such research is made possible by the wealth of radiotracers available for PET, by the fact that metabolic and kinetic parameters of particular processes can be extracted from PET data and by the continuous development of imaging techniques. In recent years great advancements have been made in the areas of PET instrumentation, data quantification and image reconstruction that allow for more detailed and accurate biological information to be extracted from PET data. It is now possible to quantitatively compare data obtained either with different tracers or with the same tracer under different scanning conditions. These sophisticated imaging approaches enable detailed investigation of disease mechanisms and system response to disease and/or therapy.

  20. The Crosstalk between Hypoxia and Innate Immunity in the Development of Obesity-Related Nonalcoholic Fatty Liver Disease

    PubMed Central

    Arias-Loste, María Teresa; Fábrega, Emilio; López-Hoyos, Marcos; Crespo, Javier

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become a major health issue in western countries in parallel with the dramatic increase in the prevalence of obesity and all obesity related conditions, including respiratory diseases as obstructive sleep apnea-hypopnea syndrome (OSAHS). Interestingly, the severity of the liver damage in obesity-related NAFLD has been associated with the concomitant presence of OSAHS. In the presence of obesity, the proinflammatory state in these patients together with intermittent episodes of hypoxia, characteristic of OSAHS pathogenesis, may lead to an enhanced inflammatory response mediated by a positive feedback loop mechanism that implicates HIF-1 and NFκB. Thus, the severity of liver involvement in obese NAFLD patients with a concomitant diagnosis of OSAHS could be explained. In this review, we focus on the molecular mechanisms underlying the hepatic response to chronic intermittent hypoxia and its interaction with innate immunity in obesity-related NAFLD. PMID:26491664

  1. Erythropoietin in sickle cell disease: relation of erythropoietin levels to crisis and other complications.

    PubMed

    Haddy, T B

    1982-01-01

    Erythropoietin responsible for the hormonal regulation of red blood cell production. Its formation is largely controlled by the kidneys. A number of assay methods for erythropoietin are available. Asymptomatic patients with sickle cell disease have elevated erythropoietin levels, as expected with chronic hemolysis. When complicated by chronic renal failure, erythropoietin levels do not rise appropriately. Chronic infection has not been studied, but the erythropoietin response in acute infection does not seem to conform to a pattern. Aplastic crises are characterized by very high levels of erythropoietin, suggesting bone marrow suppression, but events that trigger the crises remain obscure. In vaso-occlusive crises, there is also some suggestion of mild and transient lack of bone marrow response. Patients with sickle cell disease, with their chronic high erythropoietin anemia and susceptibility to altered states, are uniquely suited for investigating the physiology of erythropoietin, especially under the constraints of present assay methods.

  2. The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes.

    PubMed

    Bekkering, Pjotr; Jafri, Ismael; van Overveld, Frans J; Rijkers, Ger T

    2013-11-01

    It has been proposed that changes in the composition of gut microbiota contribute to the development of diabetes Types 1, 2 and 3 (the latter known as Alzheimer's disease). The onset of these diseases is affected by complex interactions of genetic and several environmental factors. Alterations in gut microbiota in combination with specific diets can result in increased intestinal permeability leading via a continuous state of low-grade inflammation to the development of insulin resistance. Since a change in composition of gut microbiota is also suggested to be the underlying factor for the development of obesity, it is obvious to link gut microbiota with the pathogenesis of diabetes. In addition, insulin resistance in the brain has been recently associated with Alzheimer's disease. These new paradigms in combination with data from studies with prebiotics and probiotics may lead to a novel way to control and even prevent diabetes in general.

  3. Leprosy in the Bible.

    PubMed

    Grzybowski, Andrzej; Nita, Małgorzata

    2016-01-01

    For many years, the biblical term tzaraat has referred to leprosy. In fact, the disease or diseases described under this name have no relationship to leprosy, as it was known in the Middle Ages or today; moreover, the term referred not only to skin disease, but also to the state of the ritual impurity and punishment for the sins. Although the real nature of tzaraat remains unknown, the differential diagnosis might include the following: Psoriasis, seborrheic dermatitis, favus, dermatophyte infections, nummular dermatitis, atopic dermatitis, pityriasis rosea, crusted scabies, syphilis, impetigo, sycosis barbae, alopecia areata, furuncles, scabies, neurodermatitis, scarlet fever, lupus erythematosus, lichen sclerosus et atrophicus, folliculitis decalvans, morphea, sarcoidosis, and lichen planopilaris. Leprosy became interchangeable with the biblical leprosy due to two inaccurate translations: The Hebrew tzaraat was first translated into Greek as leprosy in the sixth century, and later, the word leprosy was translated into Arabic as lepra in the ninth century. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Differential proteome analysis of diabetes mellitus type 2 and its pathophysiological complications.

    PubMed

    Sohail, Waleed; Majeed, Fatimah; Afroz, Amber

    2018-06-11

    The prevalence of Diabetes Mellitus Type 2 (DM 2) is increasing every passing year due to some global changes in lifestyles of people. The exact underlying mechanisms of the progression of this disease are not yet known. However recent advances in the combined omics more particularly in proteomics and genomics have opened a gateway towards the understanding of predetermined genetic factors, progression, complications and treatment of this disease. Here we shall review the recent advances in proteomics that have led to an early and better diagnostic approaches in controlling DM 2 more importantly the comparison of structural and functional protein biomarkers that are modified in the diseased state. By applying these advanced and promising proteomic strategies with bioinformatics applications and bio-statistical tools the prevalence of DM 2 and its associated disorders i-e nephropathy and retinopathy are expected to be controlled. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  5. Sliding mode control of outbreaks of emerging infectious diseases.

    PubMed

    Xiao, Yanni; Xu, Xiaxia; Tang, Sanyi

    2012-10-01

    This paper proposes and analyzes a mathematical model of an infectious disease system with a piecewise control function concerning threshold policy for disease management strategy. The proposed models extend the classic models by including a piecewise incidence rate to represent control or precautionary measures being triggered once the number of infected individuals exceeds a threshold level. The long-term behaviour of the proposed non-smooth system under this strategy consists of the so-called sliding motion-a very rapid switching between application and interruption of the control action. Model solutions ultimately approach either one of two endemic states for two structures or the sliding equilibrium on the switching surface, depending on the threshold level. Our findings suggest that proper combinations of threshold densities and control intensities based on threshold policy can either preclude outbreaks or lead the number of infected to a previously chosen level.

  6. The impact of Alzheimer disease genetics on expert and advanced gerontological nursing practice.

    PubMed

    Schutte, D L

    1998-11-01

    Alzheimer disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the United States, affecting as many as 4 million people. Extensive research is under way to identify environmental and genetic risk factors for this complex disease. Currently, four genes are associated with an increased risk for AD: the amyloid precursor protein gene on chromosome 21, the Presenilin I gene on chromosome 14, the Presenilin II gene on chromosome 1, and the apolipoprotein E gene on chromosome 19. Expert and advanced practice gerontological nurses are faced with new challenges as a result of these gene discoveries. Gerontological nurses should assess for relevant environmental and genetic risk factors; obtain comprehensive family health histories recorded as pedigrees; integrate genetic information into diagnosis, intervention, and evaluation strategies; initiate and coordinate referrals to genetic specialists; and provide ongoing emotional and decision-making support for patients and families experiencing AD.

  7. An assay to image neuronal microtubule dynamics in mice.

    PubMed

    Kleele, Tatjana; Marinković, Petar; Williams, Philip R; Stern, Sina; Weigand, Emily E; Engerer, Peter; Naumann, Ronald; Hartmann, Jana; Karl, Rosa M; Bradke, Frank; Bishop, Derron; Herms, Jochen; Konnerth, Arthur; Kerschensteiner, Martin; Godinho, Leanne; Misgeld, Thomas

    2014-09-12

    Microtubule dynamics in neurons play critical roles in physiology, injury and disease and determine microtubule orientation, the cell biological correlate of neurite polarization. Several microtubule binding proteins, including end-binding protein 3 (EB3), specifically bind to the growing plus tip of microtubules. In the past, fluorescently tagged end-binding proteins have revealed microtubule dynamics in vitro and in non-mammalian model organisms. Here, we devise an imaging assay based on transgenic mice expressing yellow fluorescent protein-tagged EB3 to study microtubules in intact mammalian neurites. Our approach allows measurement of microtubule dynamics in vivo and ex vivo in peripheral nervous system and central nervous system neurites under physiological conditions and after exposure to microtubule-modifying drugs. We find an increase in dynamic microtubules after injury and in neurodegenerative disease states, before axons show morphological indications of degeneration or regrowth. Thus increased microtubule dynamics might serve as a general indicator of neurite remodelling in health and disease.

  8. Applications of condensed matter understanding to medical tissues and disease progression: Elemental analysis and structural integrity of tissue scaffolds

    NASA Astrophysics Data System (ADS)

    Bradley, D. A.; Farquharson, M. J.; Gundogdu, O.; Al-Ebraheem, Alia; Che Ismail, Elna; Kaabar, W.; Bunk, O.; Pfeiffer, F.; Falkenberg, G.; Bailey, M.

    2010-02-01

    The investigations reported herein link tissue structure and elemental presence with issues of environmental health and disease, exemplified by uptake and storage of potentially toxic elements in the body, the osteoarthritic condition and malignancy in the breast and other soft tissues. Focus is placed on application of state-of-the-art ionizing radiation techniques, including, micro-synchrotron X-ray fluorescence (μ-SXRF) and particle-induced X-ray emission/Rutherford backscattering mapping (μ-PIXE/RBS), coherent small-angle X-ray scattering (cSAXS) and X-ray phase-contrast imaging, providing information on elemental make-up, the large-scale organisation of collagen and anatomical features of moderate and low atomic number media. For the particular situations under investigation, use of such facilities is allowing information to be obtained at an unprecedented level of detail, yielding new understanding of the affected tissues and the progression of disease.

  9. American College of Cardiology/American Heart Association (ACC/AHA) Class I Guidelines for the Treatment of Cholesterol to Reduce Atherosclerotic Cardiovascular Risk: Implications for US Hispanics/Latinos Based on Findings From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

    PubMed

    Qureshi, Waqas T; Kaplan, Robert C; Swett, Katrina; Burke, Gregory; Daviglus, Martha; Jung, Molly; Talavera, Gregory A; Chirinos, Diana A; Reina, Samantha A; Davis, Sonia; Rodriguez, Carlos J

    2017-05-11

    The prevalence estimates of statin eligibility among Hispanic/Latinos living in the United States under the new 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol treatment guidelines are not known. We estimated prevalence of statin eligibility under 2013 ACC/AHA and 3rd National Cholesterol Education Program Adult Treatment Panel (NCEP/ATP III) guidelines among Hispanic Community Health Study/Study of Latinos (n=16 415; mean age 41 years, 40% males) by using sampling weights calibrated to the 2010 US census. We examined the characteristics of Hispanic/Latinos treated and not treated with statins under both guidelines. We also redetermined the statin-therapy eligibility by using black risk estimates for Dominicans, Cubans, Puerto Ricans, and Central Americans. Compared with NCEP/ATP III guidelines, statin eligibility increased from 15.9% (95% CI 15.0-16.7%) to 26.9% (95% CI 25.7-28.0%) under the 2013 ACC/AHA guidelines. This was mainly driven by the ≥7.5% atherosclerotic cardiovascular disease risk criteria (prevalence 13.9% [95% CI 13.0-14.7%]). Of the participants eligible for statin eligibility under NCEP/ATP III and ACC/AHA guidelines, only 28.2% (95% CI 26.3-30.0%) and 20.6% (95% CI 19.4-21.9%) were taking statins, respectively. Statin-eligible participants who were not taking statins had a higher prevalence of cardiovascular risk factors compared with statin-eligible participants who were taking statins. There was no significant increase in statin eligibility when atherosclerotic cardiovascular disease risk was calculated by using black estimates instead of recommended white estimates (increase by 1.4%, P =0.12) for Hispanic/Latinos. The eligibility of statin therapy increased consistently across all Hispanic/Latinos subgroups under the 2013 ACC/AHA guidelines and therefore will potentially increase the number of undertreated Hispanic/Latinos in the United States. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  10. [Chronic kidney disease - The relevant information for an occupational physician].

    PubMed

    Renke, Marcin; Parszuto, Jacek; Rybacki, Marcin; Wołyniec, Wojciech; Rutkowski, Przemysław; Rutkowski, Bolesław; Walusiak-Skorupa, Jolanta; Dębska-Ślizień, Alicja

    2018-01-01

    For a number of years chronic kidney disease (CKD) has been listed in the group of lifestyle diseases, such as obesity, diabetes, cardiovascular disease and hypertension. It is estimated that in Poland more than 4 million people may suffer from various stages of CKD. Chronic kidney disease may also be a consequence of all the other civilization diseases. At the same time it is worth noting that nephrological problems are increasingly being taken into account in modern medical certification. The aim of this work is, among other things, to improve safe access to the labor for patients with kidney diseases. In the legislation existing in our country since 2014 it is stated that chronic renal failure is a potential health contraindication to driving. Also in the annex to the Regulation of the Minister of Health dated 9 December 2015 on health conditions required for seafarers to work on a seagoing ship, it is said that ICD-10 codes (International Classification of Diseases) corresponding to acute and chronic renal failure (N17-N19) should be taken into account when qualifying employees to work at sea. Med Pr 2018;69(1):67-75. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  11. Waterborne Disease Outbreaks— United States, 2009–2014

    EPA Science Inventory

    Background: The Centers for Disease Control and Prevention (CDC) has conducted national surveillance for waterborne disease outbreaks since 1971 in partnership with the Council of State and Territorial Epidemiologists and the United States Environmental Protection Agency (USEPA)....

  12. Parameter estimation and sensitivity analysis for a mathematical model with time delays of leukemia

    NASA Astrophysics Data System (ADS)

    Cândea, Doina; Halanay, Andrei; Rǎdulescu, Rodica; Tǎlmaci, Rodica

    2017-01-01

    We consider a system of nonlinear delay differential equations that describes the interaction between three competing cell populations: healthy, leukemic and anti-leukemia T cells involved in Chronic Myeloid Leukemia (CML) under treatment with Imatinib. The aim of this work is to establish which model parameters are the most important in the success or failure of leukemia remission under treatment using a sensitivity analysis of the model parameters. For the most significant parameters of the model which affect the evolution of CML disease during Imatinib treatment we try to estimate the realistic values using some experimental data. For these parameters, steady states are calculated and their stability is analyzed and biologically interpreted.

  13. Costs of colorectal cancer in different states of the disease.

    PubMed

    Färkkilä, Niilo; Torvinen, Saku; Sintonen, Harri; Saarto, Tiina; Järvinen, Heikki; Hänninen, Juha; Taari, Kimmo; Roine, Risto P

    2015-04-01

    This cross-sectional study estimates the resource use and costs among prevalent colorectal cancer (CRC) patients in different states of the disease. Altogether 508 Finnish CRC patients (aged 26-96; colon cancer 56%; female 47%) answered a questionnaire enquiring about informal care, work capacity, and demographic factors. Furthermore, data on direct medical resource use and productivity costs were obtained from registries. Patients were divided into five mutually exclusive groups based on the disease state and the time from diagnosis: primary treatments (the first six months after the diagnosis), rehabilitation, remission, metastatic disease, and palliative care. The costs were calculated for a six-month period. Multivariate modeling was performed to find the cost drivers. The costs were highest during the primary treatment state and the advanced disease states. The total costs for the cross-sectional six-month period were €22 200 in the primary treatment state, €2106 in the rehabilitation state, €2812 in the remission state, €20 540 in the metastatic state, and €21 146 in the palliative state. Most of the costs were direct medical costs. The informal care cost was highest per patient in the palliative care state, amounting to 33% of the total costs. The productivity costs varied between disease states, constituting 19-40% of the total costs, and were highest in the primary treatment state. The first six months after the diagnosis of CRC are resource intensive, but compared with the metastatic disease state, which lasts on average for 2-3 years, the costs are rather modest. Informal care constitutes a remarkable share of the total costs, especially in the palliative state. These results form a basis for the evaluation of the cost effectiveness of new treatments when allocating resources in CRC treatment.

  14. Climate change and the emergence of vector-borne diseases in Europe: case study of dengue fever.

    PubMed

    Bouzid, Maha; Colón-González, Felipe J; Lung, Tobias; Lake, Iain R; Hunter, Paul R

    2014-08-22

    Dengue fever is the most prevalent mosquito-borne viral disease worldwide. Dengue transmission is critically dependent on climatic factors and there is much concern as to whether climate change would spread the disease to areas currently unaffected. The occurrence of autochthonous infections in Croatia and France in 2010 has raised concerns about a potential re-emergence of dengue in Europe. The objective of this study is to estimate dengue risk in Europe under climate change scenarios. We used a Generalized Additive Model (GAM) to estimate dengue fever risk as a function of climatic variables (maximum temperature, minimum temperature, precipitation, humidity) and socioeconomic factors (population density, urbanisation, GDP per capita and population size), under contemporary conditions (1985-2007) in Mexico. We then used our model estimates to project dengue incidence under baseline conditions (1961-1990) and three climate change scenarios: short-term 2011-2040, medium-term 2041-2070 and long-term 2071-2100 across Europe. The model was used to calculate average number of yearly dengue cases at a spatial resolution of 10 × 10 km grid covering all land surface of the currently 27 EU member states. To our knowledge, this is the first attempt to model dengue fever risk in Europe in terms of disease occurrence rather than mosquito presence. The results were presented using Geographical Information System (GIS) and allowed identification of areas at high risk. Dengue fever hot spots were clustered around the coastal areas of the Mediterranean and Adriatic seas and the Po Valley in northern Italy. This risk assessment study is likely to be a valuable tool assisting effective and targeted adaptation responses to reduce the likely increased burden of dengue fever in a warmer world.

  15. Surgical Treatment of Hepatocellular Carcinoma

    PubMed Central

    Zamora-Valdes, Daniel; Taner, Timucin; Nagorney, David M.

    2017-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach. PMID:28975836

  16. Annosus Root Disease in Europe and the Southeastern United States: Occurrence, Research, and Historical Perspective

    Treesearch

    William J. Stambaugh

    1989-01-01

    The history of annosus root disease in Europe and the southeastern United States is reviewed in prefacing the focus of this symposium on the disease as it occurs in the western United States. The topic is developed mostly from world literature on the disease published since mid-1970. The occurrence of annosus root disease in both plantations and natural stands of...

  17. Effect of Medicaid Disease Management Programs on Emergency Admissions and Inpatient Costs

    PubMed Central

    Conti, Matthew S

    2013-01-01

    Objective To determine the impact of state Medicaid diabetes disease management programs on emergency admissions and inpatient costs. Data National InPatient Sample sponsored by the Agency for Healthcare Research and Quality Project for the years from 2000 to 2008 using 18 states. Study Design A difference-in-difference methodology compares costs and number of emergency admissions for Washington, Texas, and Georgia, which implemented disease management programs between 2000 and 2008, to states that did not undergo the transition to managed care (N = 103). Data Extraction Costs and emergency admissions were extracted for diabetic Medicaid enrollees diagnosed in the reform and non-reform states and collapsed into state and year cells. Principal Findings In the three treatment states, the implementation of disease management programs did not have statistically significant impacts on the outcome variables when compared to the control states. Conclusions States that implemented disease management programs did not achieve improvements in costs or the number of emergency of admissions; thus, these programs do not appear to be an effective way to reduce the burden of this chronic disease. PMID:23278435

  18. Effect of Medicaid disease management programs on emergency admissions and inpatient costs.

    PubMed

    Conti, Matthew S

    2013-08-01

    To determine the impact of state Medicaid diabetes disease management programs on emergency admissions and inpatient costs. National InPatient Sample sponsored by the Agency for Healthcare Research and Quality Project for the years from 2000 to 2008 using 18 states. A difference-in-difference methodology compares costs and number of emergency admissions for Washington, Texas, and Georgia, which implemented disease management programs between 2000 and 2008, to states that did not undergo the transition to managed care (N = 103). Costs and emergency admissions were extracted for diabetic Medicaid enrollees diagnosed in the reform and non-reform states and collapsed into state and year cells. In the three treatment states, the implementation of disease management programs did not have statistically significant impacts on the outcome variables when compared to the control states. States that implemented disease management programs did not achieve improvements in costs or the number of emergency of admissions; thus, these programs do not appear to be an effective way to reduce the burden of this chronic disease. © Health Research and Educational Trust.

  19. Assessment and clinical implications of cognitive impairment in acutely ill geriatric patients using a revised simplified short-term memory recall test (STMT-R).

    PubMed

    Yamamoto, Hiroshi; Ogawa, Kenichi; Huaman Battifora, Henry; Yamamuro, Kaori; Ishitake, Tatsuya

    2018-05-24

    Cognitive dysfunction due to delirium or dementia is a common finding in acutely ill geriatric patients, but often remains undetected. A brief and sensitive clinical identification method could prevent errors or complications while evaluating the mental status of elderly patients. To evaluate the usefulness and clinical implications of the revised simplified short-term memory recall test (STMT-R) in geriatric patients admitted in the emergency department; with age, gender, dementia history, serum albumin, underlying diseases and clinical outcome used as comparative factors. Mini-mental state examination and STMT-R scores were initially compared and a positive correlation was observed (r = 0.66, p < 0.001). Subsequently, 885 inpatients aged over 50 years underwent STMT-R evaluation between October 2014 and September 2015. We considered as cognitive dysfunction STMT-R scores ≤ 4 of a maximum score of 8. Among enrolled patients, 52.2% were female and the mean age was 78.9 years. There were 159 patients who were unable to complete the test (incomplete testing group). We observed cognitive dysfunction in 460 patients, while 266 did not have cognitive dysfunction. There were significant differences between those with and without cognitive dysfunction in terms of age, dementia history, underlying respiratory diseases, and hospital outcome. Cognitive dysfunction at admission can have a negative effect on the hospital outcomes of elderly patients. Age, a history of dementia and underlying respiratory diseases may also influence cognitive functional decline.

  20. Time trends of US hospitalization for esophageal disease.

    PubMed

    Sonnenberg, Amnon

    2014-09-01

    The occurrence of reflux disease seems to be rising in the United States. The aim of the present study was to follow the time trends of hospitalization for gastroesophageal reflux disease (GERD) and other esophageal disease during the past 4 decades. US hospital utilization data were available for individual years from 1970 to 2010 through the National Hospital Discharge Survey. Esophageal diagnoses were stratified by their ninth revision of the International Classification of Diseases codes. Annual hospitalizations were expressed as rates per 100,000 living US population. GERD was by far the most common esophageal disorder resulting in hospitalization. However, in only 5% of instances did GERD-related diagnoses constitute the primary cause of hospitalization. Between 1970 and 2010 the rates of GERD-related hospitalizations increased in an exponential manner almost 10-fold. This rise affected both sex and all age groups alike. A 3-fold rise was noted in hospitalizations for esophageal adenocarcinoma. Other esophageal diagnoses, such as achalasia, dyskinesia, or stricture were characterized by falling or stable trends. US hospitalization data show a continued exponential rise in the occurrence of GERD without any signs of leveling off. These trends are likely to represent ongoing changes in the underlying incidence and prevalence of the disease.

  1. N-acetyl cysteine reverts the proinflammatory state induced by cigarette smoke extract in lung Calu-3 cells.

    PubMed

    Valdivieso, Ángel G; Dugour, Andrea V; Sotomayor, Verónica; Clauzure, Mariángeles; Figueroa, Juan M; Santa-Coloma, Tomás A

    2018-06-01

    Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are lethal pulmonary diseases. Cigarette consumption is the main cause for development of COPD, while CF is produced by mutations in the CFTR gene. Although these diseases have a different etiology, both share a CFTR activity impairment and proinflammatory state even under sterile conditions. The aim of this work was to study the extent of the protective effect of the antioxidant N-acetylcysteine (NAC) over the proinflammatory state (IL-6 and IL-8), oxidative stress (reactive oxygen species, ROS), and CFTR levels, caused by Cigarette Smoke Extract (CSE) in Calu-3 airway epithelial cells. CSE treatment (100 µg/ml during 24 h) decreased CFTR mRNA expression and activity, and increased the release of IL-6 and IL-8. The effect on these cytokines was inhibited by N-acetyl cysteine (NAC, 5 mM) or the NF-kB inhibitor, IKK-2 (10 µM). CSE treatment also increased cellular and mitochondrial ROS levels. The cellular ROS levels were normalized to control values by NAC treatment, although significant effects on mitochondrial ROS levels were observed only at short times (5´) and effects on CFTR levels were not observed. In addition, CSE reduced the mitochondrial NADH-cytochrome c oxidoreductase (mCx I-III) activity, an effect that was not reverted by NAC. The reduced CFTR expression and the mitochondrial damage induced by CSE could not be normalized by NAC treatment, evidencing the need for a more specific reagent. In conclusion, CSE causes a sterile proinflammatory state and mitochondrial damage in Calu-3 cells that was partially recovered by NAC treatment. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Spatial patterns of leprosy in a hyperendemic state in Northern Brazil, 2001-2012

    PubMed Central

    Monteiro, Lorena Dias; Martins-Melo, Francisco Rogerlândio; Brito, Aline Lima; Alencar, Carlos Henrique; Heukelbach, Jorg

    2015-01-01

    ABSTRACT OBJECTIVE To describe the spatial patterns of leprosy in the Brazilian state of Tocantins. METHODS This study was based on morbidity data obtained from the Sistema de Informações de Agravos de Notificação (SINAN – Brazilian Notifiable Diseases Information System), of the Ministry of Health. All new leprosy cases in individuals residing in the state of Tocantins, between 2001 and 2012, were included. In addition to the description of general disease indicators, a descriptive spatial analysis, empirical Bayesian analysis and spatial dependence analysis were performed by means of global and local Moran’s indexes. RESULTS A total of 14,542 new cases were recorded during the period under study. Based on the annual case detection rate, 77.0% of the municipalities were classified as hyperendemic (> 40 cases/100,000 inhabitants). Regarding the annual case detection rate in < 15 years-olds, 65.4% of the municipalities were hyperendemic (10.0 to 19.9 cases/100,000 inhabitants); 26.6% had a detection rate of grade 2 disability cases between 5.0 and 9.9 cases/100,000 inhabitants. There was a geographical overlap of clusters of municipalities with high detection rates in hyperendemic areas. Clusters with high disease risk (global Moran’s index: 0.51; p < 0.001), ongoing transmission (0.47; p < 0.001) and late diagnosis (0.44; p < 0.001) were identified mainly in the central-north and southwestern regions of Tocantins. CONCLUSIONS We identified high-risk clusters for transmission and late diagnosis of leprosy in the Brazilian state of Tocantins. Surveillance and control measures should be prioritized in these high-risk municipalities. PMID:26603352

  3. Different dynamic resting state fMRI patterns are linked to different frequencies of neural activity

    PubMed Central

    Thompson, Garth John; Pan, Wen-Ju

    2015-01-01

    Resting state functional magnetic resonance imaging (rsfMRI) results have indicated that network mapping can contribute to understanding behavior and disease, but it has been difficult to translate the maps created with rsfMRI to neuroelectrical states in the brain. Recently, dynamic analyses have revealed multiple patterns in the rsfMRI signal that are strongly associated with particular bands of neural activity. To further investigate these findings, simultaneously recorded invasive electrophysiology and rsfMRI from rats were used to examine two types of electrical activity (directly measured low-frequency/infraslow activity and band-limited power of higher frequencies) and two types of dynamic rsfMRI (quasi-periodic patterns or QPP, and sliding window correlation or SWC). The relationship between neural activity and dynamic rsfMRI was tested under three anesthetic states in rats: dexmedetomidine and high and low doses of isoflurane. Under dexmedetomidine, the lightest anesthetic, infraslow electrophysiology correlated with QPP but not SWC, whereas band-limited power in higher frequencies correlated with SWC but not QPP. Results were similar under isoflurane; however, the QPP was also correlated to band-limited power, possibly due to the burst-suppression state induced by the anesthetic agent. The results provide additional support for the hypothesis that the two types of dynamic rsfMRI are linked to different frequencies of neural activity, but isoflurane anesthesia may make this relationship more complicated. Understanding which neural frequency bands appear as particular dynamic patterns in rsfMRI may ultimately help isolate components of the rsfMRI signal that are of interest to disorders such as schizophrenia and attention deficit disorder. PMID:26041826

  4. The quality of Indigenous identification in administrative health data in Australia: insights from studies using data linkage

    PubMed Central

    2012-01-01

    Background Missing or incorrect Indigenous status in health records hinders monitoring of Indigenous health indicators. Linkage of administrative data has been used to improve the ascertainment of Indigenous status. Data linkage was pioneered in Western Australia (WA) and is now being used in other Australian states. This systematic review appraises peer-reviewed Australian studies that used data linkage to elucidate the impact of under-ascertainment of Indigenous status on health indicators. Methods A PubMed search identified eligible studies that used Australian linked data to interrogate Indigenous identification using more than one identifier and interrogated the impact of the different identifiers on estimation of Indigenous health indicators. Results Eight papers were included, five from WA and three from New South Wales (NSW). The WA papers included a self-identified Indigenous community cohort and showed improved identification in hospital separation data after 2000. In CVD hospitalised patients (2000–05), under-identification was greater in urban residents, older people and socially more advantaged Indigenous people, with varying algorithms giving different estimates of under-count. Age-standardised myocardial infarction incidence rates (2000–2004) increased by about 10%-15% with improved identification. Under-ascertainment of Indigenous identification overestimated secular improvements in life expectancy and mortality whereas correcting infectious disease notifications resulted in lower Indigenous/ non-Indigenous rate ratios. NSW has a history of poor Indigenous identification in administrative data systems, but the NSW papers confirmed the usefulness of data linkage for improving Indigenous identification and the potential for very different estimates of Indigenous disease indicators depending upon the algorithm used for identification. Conclusions Under-identification of Indigenous status must be addressed in health analyses concerning Indigenous health differentials – they cannot be ignored or wished away. This problem can be substantially diminished through data linkage. Under-identification of Indigenous status impacts differently in different disease contexts, generally resulting in under-estimation of absolute and relative Indigenous health indicators, but may perversely overestimate Indigenous rates and differentials in the setting of stigma-associated conditions such as sexually-transmitted and blood-borne virus infections. Under-numeration in Census surveys also needs consideration to address the added problem of denominator undercounts. PMID:23157943

  5. Alternative bacteriophage life cycles: the carrier state of Campylobacter jejuni

    PubMed Central

    Siringan, Patcharin; Connerton, Phillippa L.; Cummings, Nicola J.; Connerton, Ian F.

    2014-01-01

    Members of the genus Campylobacter are frequently responsible for human enteric disease, often through consumption of contaminated poultry products. Bacteriophages are viruses that have the potential to control pathogenic bacteria, but understanding their complex life cycles is key to their successful exploitation. Treatment of Campylobacter jejuni biofilms with bacteriophages led to the discovery that phages had established a relationship with their hosts typical of the carrier state life cycle (CSLC), where bacteria and bacteriophages remain associated in equilibrium. Significant phenotypic changes include improved aerotolerance under nutrient-limited conditions that would confer an advantage to survive in extra-intestinal environments, but a lack in motility eliminated their ability to colonize chickens. Under these circumstances, phages can remain associated with a compatible host and continue to produce free virions to prospect for new hosts. Moreover, we demonstrate that CSLC host bacteria can act as expendable vehicles for the delivery of bacteriophages to new host bacteria within pre-colonized chickens. The CSLC represents an important phase in the ecology of Campylobacter bacteriophage. PMID:24671947

  6. Alternative bacteriophage life cycles: the carrier state of Campylobacter jejuni.

    PubMed

    Siringan, Patcharin; Connerton, Phillippa L; Cummings, Nicola J; Connerton, Ian F

    2014-03-26

    Members of the genus Campylobacter are frequently responsible for human enteric disease, often through consumption of contaminated poultry products. Bacteriophages are viruses that have the potential to control pathogenic bacteria, but understanding their complex life cycles is key to their successful exploitation. Treatment of Campylobacter jejuni biofilms with bacteriophages led to the discovery that phages had established a relationship with their hosts typical of the carrier state life cycle (CSLC), where bacteria and bacteriophages remain associated in equilibrium. Significant phenotypic changes include improved aerotolerance under nutrient-limited conditions that would confer an advantage to survive in extra-intestinal environments, but a lack in motility eliminated their ability to colonize chickens. Under these circumstances, phages can remain associated with a compatible host and continue to produce free virions to prospect for new hosts. Moreover, we demonstrate that CSLC host bacteria can act as expendable vehicles for the delivery of bacteriophages to new host bacteria within pre-colonized chickens. The CSLC represents an important phase in the ecology of Campylobacter bacteriophage.

  7. Immune privilege of the CNS is not the consequence of limited antigen sampling

    NASA Astrophysics Data System (ADS)

    Harris, Melissa G.; Hulseberg, Paul; Ling, Changying; Karman, Jozsef; Clarkson, Benjamin D.; Harding, Jeffrey S.; Zhang, Mengxue; Sandor, Adam; Christensen, Kelsey; Nagy, Andras; Sandor, Matyas; Fabry, Zsuzsanna

    2014-03-01

    Central nervous system (CNS) immune privilege is complex, and it is still not understood how CNS antigens are sampled by the peripheral immune system under steady state conditions. To compare antigen sampling from immune-privileged or nonprivileged tissues, we created transgenic mice with oligodendrocyte or gut epithelial cell expression of an EGFP-tagged fusion protein containing ovalbumin (OVA) antigenic peptides and tested peripheral anti-OVA peptide-specific sentinel OT-I and OT-II T cell activation. We report that oligodendrocyte or gut antigens are sampled similarly, as determined by comparable levels of OT-I T cell activation. However, activated T cells do not access the CNS under steady state conditions. These data show that afferent immunity is normally intact as there is no barrier at the antigen sampling level, but that efferent immunity is restricted. To understand how this one-sided surveillance contributes to CNS immune privilege will help us define mechanisms of CNS autoimmune disease initiation.

  8. Imaging of oxygen and hypoxia in cell and tissue samples.

    PubMed

    Papkovsky, Dmitri B; Dmitriev, Ruslan I

    2018-05-14

    Molecular oxygen (O 2 ) is a key player in cell mitochondrial function, redox balance and oxidative stress, normal tissue function and many common disease states. Various chemical, physical and biological methods have been proposed for measurement, real-time monitoring and imaging of O 2 concentration, state of decreased O 2 (hypoxia) and related parameters in cells and tissue. Here, we review the established and emerging optical microscopy techniques allowing to visualize O 2 levels in cells and tissue samples, mostly under in vitro and ex vivo, but also under in vivo settings. Particular examples include fluorescent hypoxia stains, fluorescent protein reporter systems, phosphorescent probes and nanosensors of different types. These techniques allow high-resolution mapping of O 2 gradients in live or post-mortem tissue, in 2D or 3D, qualitatively or quantitatively. They enable control and monitoring of oxygenation conditions and their correlation with other biomarkers of cell and tissue function. Comparison of these techniques and corresponding imaging setups, their analytical capabilities and typical applications are given.

  9. Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

    PubMed

    Mantovani, Alberto; Locati, Massimo

    2013-07-01

    Macrophages are present in all body compartments, including cancerous tissues, and their functions are profoundly affected by signals from the microenvironment under homeostatic and pathological conditions. Tumor-associated macrophages are a major cellular component of cancer-related inflammation and have served as a paradigm for the plasticity and functional polarization of mononuclear phagocytes. Tumor-associated macrophages can exert dual influence of cancer depending on the activation state, with classically activated (M1) and alternatively activated (M2) cells generally exerting antitumoral and protumoral functions, respectively. These are extremes in a continuum of polarization states in a universe of diversity. Tumor-associated macrophages affect virtually all aspects of tumor tissues, including stem cells, metabolism, angiogenesis, invasion, and metastasis. Progress has been made in defining signaling molecules, transcription factors, epigenetic changes, and repertoire of microRNAs underlying macrophage polarization. Preclinical and early clinical data suggest that macrophages may serve as tools for the development of innovative diagnostic and therapeutic strategies in cancer and chronic nonresolving inflammatory diseases.

  10. Lysosomal membrane permeabilization in cell death: new evidence and implications for health and disease.

    PubMed

    Serrano-Puebla, Ana; Boya, Patricia

    2016-05-01

    Recent studies have demonstrated that, in addition to their central role in cellular catabolic reactions, lysosomes are implicated in many cellular processes, including metabolism, membrane repair, and cell death. Lysosomal membrane permeabilization (LMP) has emerged as a pathway by which cell demise is regulated under physiological conditions and contributes to cell death in many pathological situations. Here, we review the latest evidence on LMP-mediated cell death, the upstream and downstream signals involved, and the role of LMP in the normal physiology of organisms. We also discuss the contributions of lysosomal damage and LMP to the pathogenic features of several disease states, such as lysosomal storage disorders and other neurodegenerative conditions. © 2015 New York Academy of Sciences.

  11. Liquid Silicone to Mitigate Plantar Pedal Pressure: A Literature Review

    PubMed Central

    Bowling, Frank L.; Metcalfe, Stuart A.; Wu, Stephanie; Boulton, Andrew J. M.; Armstrong, David G.

    2010-01-01

    Disruption of the body’s plantar fat pad can occur as a result of one of three mechanisms: simple fat pad atrophy associated with age-related degeneration, steroid use, or collagen vascular disease. Actual or relative displacement in to the underlying osseous prominences may be seen in association with structural deformity of the foot. Disease states such as diabetes may alter the normal structural integrity of soft tissues through nonenzymatic glycation leading to increased stiffness and thus reduced attenuating capacity. Fat pad atrophy, regardless of the cause, is often associated with substantial emotional, physical, productivity, and financial losses. In situations where the patient is sensate, the resultant skin on bone situation is extremely painful, especially when walking. PMID:20663447

  12. Animal models of fibromyalgia

    PubMed Central

    2013-01-01

    Animal models of disease states are valuable tools for developing new treatments and investigating underlying mechanisms. They should mimic the symptoms and pathology of the disease and importantly be predictive of effective treatments. Fibromyalgia is characterized by chronic widespread pain with associated co-morbid symptoms that include fatigue, depression, anxiety and sleep dysfunction. In this review, we present different animal models that mimic the signs and symptoms of fibromyalgia. These models are induced by a wide variety of methods that include repeated muscle insults, depletion of biogenic amines, and stress. All potential models produce widespread and long-lasting hyperalgesia without overt peripheral tissue damage and thus mimic the clinical presentation of fibromyalgia. We describe the methods for induction of the model, pathophysiological mechanisms for each model, and treatment profiles. PMID:24314231

  13. [Modernization, medicine, disease, and public health in Caracas (1870-1877)].

    PubMed

    Colmenares, Germán Yépez

    2002-01-01

    Between 1870 and 1877, under German Antonio Guzmán Blanco's first period of government, a set of measures was inaugurated with the intent of modernizing Venezuelan society, government, and the State. The city of Caracus was a prime setting in which to undertake a series of reformist works and measures meant to transform the capital into an urban space boasting features similar to Europe's major cities. Standing among the years' main developments are the pactice and teaching of medicine, measures seeking to improve public health conditions, and the express desire to use legal norms and resolutions to attack the principle diseases afflicting Caracas residents. The government and its circle of professional elites sought to set the stage to attract capital and European immigrants.

  14. Understanding Neuropathic Corneal Pain-Gaps and Current Therapeutic Approaches

    PubMed Central

    Goyal, Sunali; Hamrah, Pedram

    2017-01-01

    The richly innervated corneal tissue is one of the most powerful pain generator in the body. Corneal neuropathic pain results from dysfunctional nerves causing perceptions such as burning, stinging, eye-ache and pain. Various inflammatory diseases, neurological diseases, and surgical interventions can be the underlying cause of corneal neuropathic pain. Recent efforts have been made by the scientific community to elucidate the pathophysiology and neurobiology of pain resulting from initially protective physiological reflexes, to a more persistent chronic state. The goal of this clinical review is to briefly summarize the pathophysiology of neuropathic corneal pain, describe how to systematically approach the diagnosis of these patients, and finally summarizing our experience with current therapeutic approaches for the treatment of corneal neuropathic pain. PMID:26959131

  15. An assessment of Movement Disorder Society Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease.

    PubMed

    Uysal-Cantürk, P; Hanağası, H A; Bilgiç, B; Gürvit, H; Emre, M

    2018-01-01

    Cognitive impairment is one of the most disabling non-motor symptoms of Parkinson's disease. Mild cognitive impairment constitutes a major risk for the development of Parkinson's disease dementia in the course of the disease. A Movement Disorder Society Task Force proposed diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI), comprising two operational levels: Level I and Level II. The objective of our study was to test the accuracy of Level I versus Level II diagnostic criteria. Eighty-six consecutive patients with Parkinson's disease were screened and 68 patients without dementia or depression were included in the study. We used the Montreal Cognitive Assessment, Mini-Mental State Examination and Addenbrooke's Cognitive Evaluation-R screening tools for Level I and an extensive neuropsychological battery for Level II assessment. We first diagnosed PD-MCI on the basis of Level II assessment and then calculated sensitivity, specificity and area under the receiver-operator characteristics curve, comparing the performance of the three screening batteries. None of the three screening batteries proposed for Level I assessment provided satisfactory combined sensitivity and specificity for detecting PD-MCI, and their performance was similar. Using the Level II criteria, 29 patients (43%) were diagnosed as having PD-MCI. Lowest cut-off levels that provided at least 80% sensitivity were 24 for the Montreal Cognitive Assessment, 29 for the Mini-Mental State Examination and 87 for the Addenbrooke's Cognitive Evaluation-R. However, specificity levels were below 80% at these cut-off levels. We conclude that Level I assessment alone using screening batteries is not sufficiently sensitive/specific to detect PD-MCI. © 2017 EAN.

  16. Occupational contact dermatitis I: incidence and return to work pressures.

    PubMed

    Emmett, Edward A

    2002-03-01

    Since the passage of the United States Occupational Safety and Health Act (OSHA) in 1970, there have been extensive changes in United States workplaces that should have served to enhance the prevention of occupational skin disease (OSD). Analysis of skin diseases reported to OSHA (OSHA recordables) shows that the number of OSDs declined steadily from 1974 to 1983 to about half the previous annual incidence. After 1984, there was a modest resurgence peaking in 1994, with a subsequent decline. A similar but somewhat greater decline in the late 1990s has been observed for occupational respiratory diseases, diseases caused by toxic agents and for poisonings. Likely explanations for the trends in OSD are discussed; the initial decline probably reflected an improvement in workplace conditions, the later resurgence and decline may have been attributable to changes in recording behaviors and in worker's compensation. The decline in recorded OSD since 1996 has been fairly uniform in most major industrial sectors but has been less marked in agriculture, forestry, and fishing so that this sector has replaced manufacturing in recording the highest incidence rate. In 1999, the incidence rate of recorded OSD was 0.49 per 1,000 workers, which appears to grossly under report the true incidence. OSD now constitutes about 10% of all occupational disease cases. Currently, there is increasing emphasis in corporate and occupational medicine on reducing costs and maintaining productivity as well as in preventing occupational injuries and diseases. This is shown by the trend for a greater proportion of workers with occupational conditions to return to modified duty positions rather than to be completely off work. Implications of this phenomena for management of OSD are discussed. Copyright 2002, Elsevier Science (USA). All rights reserved.

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

    PubMed

    Antioch, Kathryn M; Walsh, Michael K

    2004-06-01

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

  18. Delirium superimposed on dementia: defining disease states and course from longitudinal measurements of a multivariate index using latent class analysis and hidden Markov chains.

    PubMed

    Ciampi, Antonio; Dyachenko, Alina; Cole, Martin; McCusker, Jane

    2011-12-01

    The study of mental disorders in the elderly presents substantial challenges due to population heterogeneity, coexistence of different mental disorders, and diagnostic uncertainty. While reliable tools have been developed to collect relevant data, new approaches to study design and analysis are needed. We focus on a new analytic approach. Our framework is based on latent class analysis and hidden Markov chains. From repeated measurements of a multivariate disease index, we extract the notion of underlying state of a patient at a time point. The course of the disorder is then a sequence of transitions among states. States and transitions are not observable; however, the probability of being in a state at a time point, and the transition probabilities from one state to another over time can be estimated. Data from 444 patients with and without diagnosis of delirium and dementia were available from a previous study. The Delirium Index was measured at diagnosis, and at 2 and 6 months from diagnosis. Four latent classes were identified: fairly healthy, moderately ill, clearly sick, and very sick. Dementia and delirium could not be separated on the basis of these data alone. Indeed, as the probability of delirium increased, so did the probability of decline of mental functions. Eight most probable courses were identified, including good and poor stable courses, and courses exhibiting various patterns of improvement. Latent class analysis and hidden Markov chains offer a promising tool for studying mental disorders in the elderly. Its use may show its full potential as new data become available.

  19. Hypersensitivity pneumonitis due to metal working fluids: Sporadic or under reported?

    PubMed

    Gupta, Amit; Rosenman, Kenneth D

    2006-06-01

    Occupational exposure to metal working fluids (MWF) is common with over 1.2 million workers in the United States involved in machine finishing, machine tooling, and other metalworking operations. MWF is a known cause of hypersensitivity pneumonitis (HP). Recent reports of outbreaks of hypersensitivity HP secondary to exposure to MWF are reported. Cases were identified through the Occupational Disease surveillance system in the State of Michigan and from referrals for evaluation to the Division of Occupational and Environmental Medicine at Michigan State University (MSU). Each patient underwent a clinical examination including an occupational history, lung function studies, radiographic imaging, and in some cases lung biopsies. Following the diagnosis of definite HP, an industrial hygiene investigation was carried out, which included a plant walk-through, and review of the "Injury and Illness" log. Air monitoring and microbial sampling results were reviewed. As part of Michigan's mandatory surveillance system for occupational illnesses, seven cases of suspected HP were identified in 2003-2004 from three facilities manufacturing automobile parts in Michigan. Each plant used semi-synthetic MWFs, and conducted a MWF management program including biocide additions. Two facilities had recently changed the MWF before the cases arose. Growth of mycobacteria was found in these two MWFs. Breathing zone samples for particulates of two employees in plant A (two cases) ranged from 0.48 to 0.56 mg/m3. In plant B (four cases), two employees' sampling results ranged from 0.10 to 0.14 mg/m3. No air sampling data were available from plant C. Hypersensitivity pneumonitis due to exposure to MWFs is under-recognized by health care providers, and current surveillance systems are inadequate to provide a true estimate of its occurrence. HP arose from environments with exposures well below the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for MWF, and in one case from exposures well below the National Institute of Occupational Safety and Health (NIOSH) recommended exposure limit (REL). The sporadic nature of reports of HP in relationship to MWF probably represents a combination of workplace changes that cause the disease and inadequate recognition and reporting of the disease when it does occur. Physician awareness of HP secondary to MWF and an effective medical surveillance program are necessary to better understanding the epidemiology and prevention of this disease.

  20. Tick-Associated Diseases: Symptoms, Treatment and Prevention

    ERIC Educational Resources Information Center

    Anderson, Alice; Chaney, Elizabeth

    2009-01-01

    According to the Centers for Disease Control and Prevention (CDC), there are eleven tick-associated diseases prevalent in the United States. Most commonly diagnosed are Lyme disease, anaplasmosis (ehrlichiosis) and babeisois, with Lyme disease being the most common vector-borne disease in the country. In southeastern states, studies have shown the…

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