Physiological changes in neurodegeneration - mechanistic insights and clinical utility.

PubMed

Ahmed, Rebekah M; Ke, Yazi D; Vucic, Steve; Ittner, Lars M; Seeley, William; Hodges, John R; Piguet, Olivier; Halliday, Glenda; Kiernan, Matthew C

2018-05-01

The effects of neurodegenerative syndromes extend beyond cognitive function to involve key physiological processes, including eating and metabolism, autonomic nervous system function, sleep, and motor function. Changes in these physiological processes are present in several conditions, including frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer disease and the parkinsonian plus conditions. Key neural structures that mediate physiological changes across these conditions include neuroendocrine and hypothalamic pathways, reward pathways, motor systems and the autonomic nervous system. In this Review, we highlight the key changes in physiological processing in neurodegenerative syndromes and the similarities in these changes between different progressive neurodegenerative brain conditions. The changes and similarities between disorders might provide novel insights into the human neural correlates of physiological functioning. Given the evidence that physiological changes can arise early in the neurodegenerative process, these changes could provide biomarkers to aid in the early diagnosis of neurodegenerative diseases and in treatment trials.

Ducks Get Sick Too!

USGS Publications Warehouse

Windingstad, Ronald M.; Laitman, Cynthia J.

1988-01-01

When it comes to getting sick, wild waterfowl—which include ducks, geese, and swans—are a lot like people. We are all vulnerable to a wide variety of diseases.Some diseases that affect waterfowl, such as avian botulism, have been recognized for many decades as a major cause of death. Others, such as duck plague, are relative newcomers to the known roster of waterfowl diseases.Unfortunately, the number of waterfowl diseases as well as disease-breeding conditions are on the increase. As human development has expanded and encroached on wetlands, more and more waterfowl have been forced into less and less habitat. The resulting crowding can promote the spread of infectious disease caused by toxicants and other noninfectious agents.Although millions of waterfowl die of disease each year, it is often difficult to "see" the disease process occurring. Sick and dying birds usually seek cover to hide, and predators and scavengers eventually devour most of them. When disease becomes epidemic (a disease epidemic in animals is called an epizootic) and sick and dead birds become too numerous for predators and scavengers to eliminate, the disease process becomes far more noticeable.The diseases described in this booklet are among the most common causes of death in wild waterfowl, and include examples of those cause by bacteria, viruses, parasites, fungi, and toxic substances.

Estimation of plant disease severity visually, by digital photography and image analysis, and by hyperspectral imaging

USDA-ARS?s Scientific Manuscript database

Reliable, precise and accurate estimates of disease severity are important for predicting yield loss, monitoring and forecasting epidemics, for assessing crop germplasm for disease resistance, and for understanding fundamental biological processes including co-evolution. In some situations poor qual...

Branching processes in disease epidemics

NASA Astrophysics Data System (ADS)

Singh, Sarabjeet

Branching processes have served as a model for chemical reactions, biological growth processes and contagion (of disease, information or fads). Through this connection, these seemingly different physical processes share some common universalities that can be elucidated by analyzing the underlying branching process. In this thesis, we focus on branching processes as a model for infectious diseases spreading between individuals belonging to different populations. The distinction between populations can arise from species separation (as in the case of diseases which jump across species) or spatial separation (as in the case of disease spreading between farms, cities, urban centers, etc). A prominent example of the former is zoonoses -- infectious diseases that spill from animals to humans -- whose specific examples include Nipah virus, monkeypox, HIV and avian influenza. A prominent example of the latter is infectious diseases of animals such as foot and mouth disease and bovine tuberculosis that spread between farms or cattle herds. Another example of the latter is infectious diseases of humans such as H1N1 that spread from one city to another through migration of infectious hosts. This thesis consists of three main chapters, an introduction and an appendix. The introduction gives a brief history of mathematics in modeling the spread of infectious diseases along with a detailed description of the most commonly used disease model -- the Susceptible-Infectious-Recovered (SIR) model. The introduction also describes how the stochastic formulation of the model reduces to a branching process in the limit of large population which is analyzed in detail. The second chapter describes a two species model of zoonoses with coupled SIR processes and proceeds into the calculation of statistics pertinent to cross species infection using multitype branching processes. The third chapter describes an SIR process driven by a Poisson process of infection spillovers. This is posed as a model of infectious diseases where a `reservoir' of infection exists that infects a susceptible host population at a constant rate. The final chapter of the thesis describes a general framework of modeling infectious diseases in a network of populations using multitype branching processes.

Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases

PubMed Central

Smith, J. A.; Leonardi, T.; Huang, B.; Iraci, N.; Vega, B.; Pluchino, S.

2015-01-01

Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs—or specific EV cargoes—are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases. PMID:24973266

Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases.

PubMed

Smith, J A; Leonardi, T; Huang, B; Iraci, N; Vega, B; Pluchino, S

2015-04-01

Multicellular organisms rely upon diverse and complex intercellular communications networks for a myriad of physiological processes. Disruption of these processes is implicated in the onset and propagation of disease and disorder, including the mechanisms of senescence at both cellular and organismal levels. In recent years, secreted extracellular vesicles (EVs) have been identified as a particularly novel vector by which cell-to-cell communications are enacted. EVs actively and specifically traffic bioactive proteins, nucleic acids, and metabolites between cells at local and systemic levels, modulating cellular responses in a bidirectional manner under both homeostatic and pathological conditions. EVs are being implicated not only in the generic aging process, but also as vehicles of pathology in a number of age-related diseases, including cancer and neurodegenerative and disease. Thus, circulating EVs-or specific EV cargoes-are being utilised as putative biomarkers of disease. On the other hand, EVs, as targeted intercellular shuttles of multipotent bioactive payloads, have demonstrated promising therapeutic properties, which can potentially be modulated and enhanced through cellular engineering. Furthermore, there is considerable interest in employing nanomedicinal approaches to mimic the putative therapeutic properties of EVs by employing synthetic analogues for targeted drug delivery. Herein we describe what is known about the origin and nature of EVs and subsequently review their putative roles in biology and medicine (including the use of synthetic EV analogues), with a particular focus on their role in aging and age-related brain diseases.

An epigenetic view of developmental diseases: new targets, new therapies.

PubMed

Xie, Pei; Zang, Li-Qun; Li, Xue-Kun; Shu, Qiang

2016-08-01

Function of epigenetic modifications is one of the most competitive fields in life science. Over the past several decades, it has been revealed that epigenetic modifications play essential roles in development and diseases including developmental diseases. In the present review, we summarize the recent progress about the function of epigenetic regulation, especially DNA and RNA modifications in developmental diseases. Original research articles and literature reviews published in PubMed-indexed journals. DNA modifications including methylation and demethylation can regulate gene expression, and are involved in development and multiple diseases including Rett syndrome, Autism spectrum disorders, congenital heart disease and cancer, etc. RNA methylation and demethylation play important roles in RNA processing, reprogramming, circadian, and neuronal activity, and then modulate development. DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

Processing of CT images for analysis of diffuse lung disease in the lung tissue research consortium

NASA Astrophysics Data System (ADS)

Karwoski, Ronald A.; Bartholmai, Brian; Zavaletta, Vanessa A.; Holmes, David; Robb, Richard A.

2008-03-01

The goal of Lung Tissue Resource Consortium (LTRC) is to improve the management of diffuse lung diseases through a better understanding of the biology of Chronic Obstructive Pulmonary Disease (COPD) and fibrotic interstitial lung disease (ILD) including Idiopathic Pulmonary Fibrosis (IPF). Participants are subjected to a battery of tests including tissue biopsies, physiologic testing, clinical history reporting, and CT scanning of the chest. The LTRC is a repository from which investigators can request tissue specimens and test results as well as semi-quantitative radiology reports, pathology reports, and automated quantitative image analysis results from the CT scan data performed by the LTRC core laboratories. The LTRC Radiology Core Laboratory (RCL), in conjunction with the Biomedical Imaging Resource (BIR), has developed novel processing methods for comprehensive characterization of pulmonary processes on volumetric high-resolution CT scans to quantify how these diseases manifest in radiographic images. Specifically, the RCL has implemented a semi-automated method for segmenting the anatomical regions of the lungs and airways. In these anatomic regions, automated quantification of pathologic features of disease including emphysema volumes and tissue classification are performed using both threshold techniques and advanced texture measures to determine the extent and location of emphysema, ground glass opacities, "honeycombing" (HC) and "irregular linear" or "reticular" pulmonary infiltrates and normal lung. Wall thickness measurements of the trachea, and its branches to the 3 rd and limited 4 th order are also computed. The methods for processing, segmentation and quantification are described. The results are reviewed and verified by an expert radiologist following processing and stored in the public LTRC database for use by pulmonary researchers. To date, over 1200 CT scans have been processed by the RCL and the LTRC project is on target for recruitment of the 2200 patients with 1800 CT scans in the repository for the 5-year effort. Ongoing analysis of the results in the LTRC database by the LTRC participating institutions and outside investigators are underway to look at the clinical and physiological significance of the imaging features of these diseases and correlate these findings with quality of life and other important prognostic indicators of severity. In the future, the quantitative measures of disease may have greater utility by showing correlation with prognosis, disease severity and other physiological parameters. These imaging features may provide non-invasive alternative endpoints or surrogate markers to alleviate the need for tissue biopsy or provide an accurate means to monitor rate of disease progression or response to therapy.

Symptoms of Depression and Anxiety in Adolescents with Sickle Cell Disease: The Role of Intrapersonal Characteristics and Stress Processing Variables

ERIC Educational Resources Information Center

Simon, Katherine; Barakat, Lamia P.; Patterson, Chavis A.; Dampier, Carlton

2009-01-01

Sickle cell disease (SCD) complications place patients at risk for poor psychosocial adaptation, including depression and anxiety symptoms. This study aimed to test a mediator model based on the Risk and Resistance model to explore the role of intrapersonal characteristics and stress processing variables in psychosocial functioning. Participants…

Natural Disasters and Cholera Outbreaks: Current Understanding and Future Outlook.

PubMed

Jutla, Antarpreet; Khan, Rakibul; Colwell, Rita

2017-03-01

Diarrheal diseases remain a serious global public health threat, especially for those populations lacking access to safe water and sanitation infrastructure. Although association of several diarrheal diseases, e.g., cholera, shigellosis, etc., with climatic processes has been documented, the global human population remains at heightened risk of outbreak of diseases after natural disasters, such as earthquakes, floods, or droughts. In this review, cholera was selected as a signature diarrheal disease and the role of natural disasters in triggering and transmitting cholera was analyzed. Key observations include identification of an inherent feedback loop that includes societal structure, prevailing climatic processes, and spatio-temporal seasonal variability of natural disasters. Data obtained from satellite-based remote sensing are concluded to have application, although limited, in predicting risks of a cholera outbreak(s). We argue that with the advent of new high spectral and spatial resolution data, earth observation systems should be seamlessly integrated in a decision support mechanism to be mobilize resources when a region suffers a natural disaster. A framework is proposed that can be used to assess the impact of natural disasters with response to outbreak of cholera, providing assessment of short- and long-term influence of climatic processes on disease outbreaks.

Synaptic Activity and Bioenergy Homeostasis: Implications in Brain Trauma and Neurodegenerative Diseases

PubMed Central

Khatri, Natasha; Man, Heng-Ye

2013-01-01

Powered by glucose metabolism, the brain is the most energy-demanding organ in our body. Adequate ATP production and regulation of the metabolic processes are essential for the maintenance of synaptic transmission and neuronal function. Glutamatergic synaptic activity utilizes the largest portion of bioenergy for synaptic events including neurotransmitter synthesis, vesicle recycling, and most importantly, the postsynaptic activities leading to channel activation and rebalancing of ionic gradients. Bioenergy homeostasis is coupled with synaptic function via activities of the sodium pumps, glutamate transporters, glucose transport, and mitochondria translocation. Energy insufficiency is sensed by the AMP-activated protein kinase (AMPK), a master metabolic regulator that stimulates the catalytic process to enhance energy production. A decline in energy supply and a disruption in bioenergy homeostasis play a critical role in multiple neuropathological conditions including ischemia, stroke, and neurodegenerative diseases including Alzheimer’s disease and traumatic brain injuries. PMID:24376435

The role of the striatum in rule application: the model of Huntington's disease at early stage.

PubMed

Teichmann, Marc; Dupoux, Emmanuel; Kouider, Sid; Brugières, Pierre; Boissé, Marie-Françoise; Baudic, Sophie; Cesaro, Pierre; Peschanski, Marc; Bachoud-Lévi, Anne-Catherine

2005-05-01

The role of the basal ganglia, and more specifically of the striatum, in language is still debated. Recent studies have proposed that linguistic abilities involve two distinct types of processes: the retrieving of stored information, implicating temporal lobe areas, and the application of combinatorial rules, implicating fronto-striatal circuits. Studies of patients with focal lesions and neurodegenerative diseases have suggested a role for the striatum in morphological rule application, but functional imaging studies found that the left caudate was involved in syntactic processing and not morphological processing. In the present study, we tested the view that the basal ganglia are involved in rule application and not in lexical retrieving in a model of striatal dysfunction, namely Huntington's disease at early stages. We assessed the rule-lexicon dichotomy in the linguistic domain with morphology (conjugation of non-verbs and verbs) and syntax (sentence comprehension) and in a non-linguistic domain with arithmetic operations (subtraction and multiplication). Thirty Huntington's disease patients (15 at stage I and 15 at stage II) and 20 controls matched for their age and cultural level were included in this study. Huntington's disease patients were also assessed using the Unified Huntington's Disease Rating Scale (UHDRS) and MRI. We found that early Huntington's disease patients were impaired in rule application in the linguistic and non-linguistic domains (morphology, syntax and subtraction), whereas they were broadly spared with lexical processing. The pattern of performance was similar in patients at stage I and stage II, except that stage II patients were more impaired in all tasks assessing rules and had in addition a very slight impairment in the lexical condition of conjugation. Finally, syntactic rule abilities correlated with all markers of the disease evolution including bicaudate ratio and performance in executive function, whereas there was no correlation with arithmetic and morphological abilities. Together, this suggests that the striatum is involved in rule processing more than in lexical processing and that it extends to linguistic and non-linguistic domains. These results are discussed in terms of domain-specific versus domain-general processes of rule application.

Nutritional programming of disease: unravelling the mechanism

PubMed Central

Langley-Evans, Simon C

2009-01-01

Nutritional programming is the process through which variation in the quality or quantity of nutrients consumed during pregnancy exerts permanent effects upon the developing fetus. Programming of fetal development is considered to be an important risk factor for non-communicable diseases of adulthood, including coronary heart disease and other disorders related to insulin resistance. The study of programming in relation to disease processes has been advanced by development of animal models, which have utilized restriction or over-feeding of specific nutrients in either rodents or sheep. These consistently demonstrate the biological plausibility of the nutritional programming hypothesis and, importantly, provide tools with which to examine the mechanisms through which programming may occur. Studies of animals subject to undernutrition in utero generally exhibit changes in the structure of key organs such as the kidney, heart and brain. These appear consistent with remodelling of development, associated with disruption of cellular proliferation and differentiation. Whilst the causal pathways which extend from this tissue remodelling to disease can be easily understood, the processes which lead to this disordered organ development are poorly defined. Even minor variation in maternal nutritional status is capable of producing important shifts in the fetal environment. It is suggested that these environmental changes are associated with altered expression of key genes, which are responsible for driving the tissue remodelling response and future disease risk. Nutrition-related factors may drive these processes by disturbing placental function, including control of materno-fetal endocrine exchanges, or the epigenetic regulation of gene expression. PMID:19175805

An approach to and web-based tool for infectious disease outbreak intervention analysis

NASA Astrophysics Data System (ADS)

Daughton, Ashlynn R.; Generous, Nicholas; Priedhorsky, Reid; Deshpande, Alina

2017-04-01

Infectious diseases are a leading cause of death globally. Decisions surrounding how to control an infectious disease outbreak currently rely on a subjective process involving surveillance and expert opinion. However, there are many situations where neither may be available. Modeling can fill gaps in the decision making process by using available data to provide quantitative estimates of outbreak trajectories. Effective reduction of the spread of infectious diseases can be achieved through collaboration between the modeling community and public health policy community. However, such collaboration is rare, resulting in a lack of models that meet the needs of the public health community. Here we show a Susceptible-Infectious-Recovered (SIR) model modified to include control measures that allows parameter ranges, rather than parameter point estimates, and includes a web user interface for broad adoption. We apply the model to three diseases, measles, norovirus and influenza, to show the feasibility of its use and describe a research agenda to further promote interactions between decision makers and the modeling community.

Preserving Self: Theorizing the Social and Psychological Processes of Living With Parkinson Disease.

PubMed

Vann-Ward, Terrie; Morse, Janice M; Charmaz, Kathy

2017-06-01

The purpose of this constructivist grounded theory article is to identify, explore, and theorize the social and psychological processes used by people with Parkinson disease. Analytic procedures generated the five-stage theory of Preserving self of people with Parkinson disease: (a) making sense of symptoms, (b) defining turning points, (c) experiencing identity dilemmas, (d) reconnecting the self, and (e) envisioning a future. Reminders of former selves and capabilities were painful; participants desperately sought normalcy. Participants developed creative methods for maintaining independence but frequently overestimated their abilities and took risks. Participants were 15 men and 10 women (ages 40-95), most of whom lived with their families. Disease status was ascertained through medication logs and two scales: Hoehn and Yahr staging and Activities of Daily Living. Data included 62 in-depth interviews, nonparticipant observation, and participant photos, videos, and related documents. Recommendations were derived from the theory to support processes of Preserving Self as interventions designed to reduce the loss of self and to enhance Preserving self. These recommendations included developing relationships, teaching expected and unexpected feelings and behaviors, and involvement with sensory integrating activities.

Parkinson's Disease: Leucine-Rich Repeat Kinase 2 and Autophagy, Intimate Enemies

PubMed Central

Bravo-San Pedro, José M.; Gómez-Sánchez, Rubén; Pizarro-Estrella, Elisa; Niso-Santano, Mireia; González-Polo, Rosa A.; Fuentes Rodríguez, José M.

2012-01-01

Parkinson's disease is the second common neurodegenerative disorder, after Alzheimer's disease. It is a clinical syndrome characterized by loss of dopamine-generating cells in the substancia nigra, a region of the midbrain. The etiology of Parkinson's disease has long been through to involve both genetic and environmental factors. Mutations in the leucine-rich repeat kinase 2 gene cause late-onset Parkinson's disease with a clinical appearance indistinguishable from Parkinson's disease idiopathic. Autophagy is an intracellular catabolic mechanism whereby a cell recycles or degrades damage proteins and cytoplasmic organelles. This degradative process has been associated with cellular dysfunction in neurodegenerative processes including Parkinson's disease. We discuss the role of leucine-rich repeat kinase 2 in autophagy, and how the deregulations of this degradative mechanism in cells can be implicated in the Parkinson's disease etiology. PMID:22970411

A system for diagnosis of wheat leaf diseases based on Android smartphone

NASA Astrophysics Data System (ADS)

Xie, Xinhua; Zhang, Xiangqian; He, Bing; Liang, Dong; Zhang, Dongyang; Huang, Linsheng

2016-10-01

Owing to the shortages of inconvenience, expensive and high professional requirements etc. for conventional recognition devices of wheat leaf diseases, it does not satisfy the requirements of uploading and releasing timely investigation data in the large-scale field, which may influence the effectiveness of prevention and control for wheat diseases. In this study, a fast, accurate, and robust diagnose system of wheat leaf diseases based on android smartphone was developed, which comprises of two parts—the client and the server. The functions of the client include image acquisition, GPS positioning, corresponding, and knowledge base of disease prevention and control. The server includes image processing, feature extraction, and selection, and classifier establishing. The recognition process of the system goes as follow: when disease images were collected in fields and sent to the server by android smartphone, and then image processing of disease spots was carried out by the server. Eighteen larger weight features were selected by algorithm relief-F and as the input of Relevance Vector Machine (RVM), and the automatic identification of wheat stripe rust and powdery mildew was realized. The experimental results showed that the average recognition rate and predicted speed of RVM model were 5.56% and 7.41 times higher than that of Support Vector Machine (SVM). And application discovered that it needs about 1 minute to get the identification result. Therefore, it can be concluded that the system could be used to recognize wheat diseases and real-time investigate in fields.

The interaction of host genetics and disease processes in chronic livestock disease: a simulation model of ovine footrot.

PubMed

Russell, V N L; Green, L E; Bishop, S C; Medley, G F

2013-03-01

A stochastic, individual-based, simulation model of footrot in a flock of 200 ewes was developed that included flock demography, disease processes, host genetic variation for traits influencing infection and disease processes, and bacterial contamination of the environment. Sensitivity analyses were performed using ANOVA to examine the contribution of unknown parameters to outcome variation. The infection rate and bacterial death rate were the most significant factors determining the observed prevalence of footrot, as well as the heritability of resistance. The dominance of infection parameters in determining outcomes implies that observational data cannot be used to accurately estimate the strength of genetic control of underlying traits describing the infection process, i.e. resistance. Further work will allow us to address the potential for genetic selection to control ovine footrot. Copyright © 2012 Elsevier B.V. All rights reserved.

A combined disease management and process modeling approach for assessing and improving care processes: a fall management case-study.

PubMed

Askari, Marjan; Westerhof, Richard; Eslami, Saied; Medlock, Stephanie; de Rooij, Sophia E; Abu-Hanna, Ameen

2013-10-01

To propose a combined disease management and process modeling approach for evaluating and improving care processes, and demonstrate its usability and usefulness in a real-world fall management case study. We identified essential disease management related concepts and mapped them into explicit questions meant to expose areas for improvement in the respective care processes. We applied the disease management oriented questions to a process model of a comprehensive real world fall prevention and treatment program covering primary and secondary care. We relied on interviews and observations to complete the process models, which were captured in UML activity diagrams. A preliminary evaluation of the usability of our approach by gauging the experience of the modeler and an external validator was conducted, and the usefulness of the method was evaluated by gathering feedback from stakeholders at an invitational conference of 75 attendees. The process model of the fall management program was organized around the clinical tasks of case finding, risk profiling, decision making, coordination and interventions. Applying the disease management questions to the process models exposed weaknesses in the process including: absence of program ownership, under-detection of falls in primary care, and lack of efficient communication among stakeholders due to missing awareness about other stakeholders' workflow. The modelers experienced the approach as usable and the attendees of the invitational conference found the analysis results to be valid. The proposed disease management view of process modeling was usable and useful for systematically identifying areas of improvement in a fall management program. Although specifically applied to fall management, we believe our case study is characteristic of various disease management settings, suggesting the wider applicability of the approach. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Autophagy at the gut interface - mucosal responses to stress and the consequences for inflammatory bowel diseases

PubMed Central

Huett, Alan; Xavier, Ramnik J.

2014-01-01

Autophagy is a conserved homeostatic process by which cells degrade and recycle cytoplasmic contents and organelles. Recently autophagy has come to prominence as a factor in many disease states, including inflammatory bowel diseases. In this review we explore the recent discoveries in autophagy and how these relate to the special conditions experienced by the gut mucosa. We will pay particular attention to autophagy as an innate immune process and its role in the development and education of the adaptive immune system. PMID:19575363

Mobile technologies for disease surveillance in humans and animals.

PubMed

Mwabukusi, Mpoki; Karimuribo, Esron D; Rweyemamu, Mark M; Beda, Eric

2014-04-23

A paper-based disease reporting system has been associated with a number of challenges. These include difficulties to submit hard copies of the disease surveillance forms because of poor road infrastructure, weather conditions or challenging terrain, particularly in the developing countries. The system demands re-entry of the data at data processing and analysis points, thus making it prone to introduction of errors during this process. All these challenges contribute to delayed acquisition, processing and response to disease events occurring in remote hard to reach areas. Our study piloted the use of mobile phones in order to transmit near to real-time data from remote districts in Tanzania (Ngorongoro and Ngara), Burundi (Muyinga) and Zambia (Kazungula and Sesheke). Two technologies namely, digital and short messaging services were used to capture and transmit disease event data in the animal and human health sectors in the study areas based on a server-client model. Smart phones running the Android operating system (minimum required version: Android 1.6), and which supported open source application, Epicollect, as well as the Open Data Kit application, were used in the study. These phones allowed collection of geo-tagged data, with the opportunity of including static and moving images related to disease events. The project supported routine disease surveillance systems in the ministries responsible for animal and human health in Burundi, Tanzania and Zambia, as well as data collection for researchers at the Sokoine University of Agriculture, Tanzania. During the project implementation period between 2011 and 2013, a total number of 1651 diseases event-related forms were submitted, which allowed reporters to include GPS coordinates and photographs related to the events captured. It was concluded that the new technology-based surveillance system is useful in providing near to real-time data, with potential for enhancing timely response in rural remote areas of Africa. We recommended adoption of the proven technologies to improve disease surveillance, particularly in the developing countries.

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

Management of Uveitis in Spondyloarthropathy: Current Trends

PubMed Central

Gupta, Nikhil; Agarwal, Aditi

2018-01-01

Spondyloarthritis is a chronic inflammatory disease predominantly affecting joints of the axial skeleton. However, as many as 50% of patients with this disease may have extra-articular manifestations, which include uveitis; psoriasis; inflammatory bowel disease such as Crohn disease or ulcerative colitis; cardiovascular manifestations in the form of conduction abnormalities, atherosclerosis, or valvular heart disease; pulmonary involvement; and rarely renal involvement. Uveitis occurs in 25% to 40% of patients with spondyloarthritis. Management of uveitis is crucial to prevent morbidity caused by vision loss and secondary complications. Treatment ranges from local therapies to systemic drugs and varies depending on the severity and response to treatment. Categories of medical treatment include nonsteroidal anti-inflammatory agents, corticosteroids, and steroid-sparing agents. Biologic therapies such as antitumor necrosis factor agents act early in the disease process and have revolutionized the field of rheumatology, including management of uveitis. This review will focus on the management of ophthalmic manifestations in spondyloarthropathies. PMID:29272246

Atherosclerotic Cardiovascular Disease Beginning in Childhood

PubMed Central

2010-01-01

Although the clinical manifestations of cardiovascular disease (CVD), such as myocardial infarction, stroke, and peripheral vascular disease, appear from middle age, the process of atherosclerosis can begin early in childhood. The early stage and progression of atherosclerosis in youth are influenced by risk factors that include obesity, hypertension, dyslipidemia, and smoking, and by the presence of specific diseases, such as diabetes mellitus and Kawasaki disease (KD). The existing evidence indicates that primary prevention of atherosclerotic disease should begin in childhood. Identification of children at risk for atherosclerosis may allow early intervention to decrease the atherosclerotic process, thereby preventing or delaying CVD. This review will describe the origin and progression of atherosclerosis in childhood, and the identification and management of known risk factors for atherosclerotic CVD in children and young adults. PMID:20111646

Potential Role of microRNAs in Cardiovascular Disease: Are They up to Their Hype?

PubMed

Duggal, Bhanu; Gupta, Manveen K; Naga Prasad, Sathyamangla V

Cardiovascular diseases remain the foremost cause of mortality globally. As molecular medicine unravels the alterations in genomic expression and regulation of the underlying atherosclerotic process, it opens new vistas for discovering novel diagnostic biomarkers and therapeutics for limiting the disease process. miRNAs have emerged as powerful regulators of protein translation by regulating gene expression at the post-transcriptional level. Overexpression and under-expression of specific miRNAs are being evaluated as a novel approach to diagnosis and treatment of cardiovascular disease. This review sheds light on the current knowledge of the miRNA evaluated in cardiovascular disease. In this review we summarize the data, including the more recent data, regarding miRNAs in cardiovascular disease and their potential role in future in diagnostic and therapeutic strategies.

Periodontal disease.

PubMed

Niemiec, Brook A

2008-05-01

Periodontal disease is the most commonly diagnosed problem in small animal veterinary medicine. In the vast majority of cases, however, there are little to no outward clinical signs of the disease process, and, therefore, therapy often comes very late in the disease course. Consequently, periodontal disease is also the most undertreated animal health problem. In addition, unchecked periodontal disease has numerous dire consequences both locally and systemically. These consequences are detailed in the article and should be utilized to educate clients and encourage compliance of therapeutic recommendations. The local consequences include oronasal fistulas, class II perio-endo lesions, pathologic fractures, ocular problems, osteomyelitis, and an increased incidence of oral cancer. Systemic diseases linked to periodontal disease include: renal, hepatic, pulmonary, and cardiac diseases; osteoporosis, adverse pregnancy effects, and diabetes mellitus. Before the discussion of consequences, this article covers the pathogenesis of periodontal disease, followed by clinical features and diagnostic tests.

Occupational Disease Registries-Characteristics and Experiences.

PubMed

Davoodi, Somayeh; Haghighi, Khosro Sadeghniat; Kalhori, Sharareh Rostam Niakan; Hosseini, Narges Shams; Mohammadzadeh, Zeinab; Safdari, Reza

2017-06-01

Due to growth of occupational diseases and also increase of public awareness about their consequences, attention to various aspects of diseases and improve occupational health and safety has found great importance. Therefore, there is the need for appropriate information management tools such as registries in order to recognitions of diseases patterns and then making decision about prevention, early detection and treatment of them. These registries have different characteristics in various countries according to their occupational health priorities. Aim of this study is evaluate dimensions of occupational diseases registries including objectives, data sources, responsible institutions, minimum data set, classification systems and process of registration in different countries. In this study, the papers were searched using the MEDLINE (PubMed) Google scholar, Scopus, ProQuest and Google. The search was done based on keyword in English for all motor engines including "occupational disease", "work related disease", "surveillance", "reporting", "registration system" and "registry" combined with name of the countries including all subheadings. After categorizing search findings in tables, results were compared with each other. Important aspects of the registries studied in ten countries including Finland, France, United Kingdom, Australia, Czech Republic, Malaysia, United States, Singapore, Russia and Turkey. The results show that surveyed countries have statistical, treatment and prevention objectives. Data sources in almost the rest of registries were physicians and employers. The minimum data sets in most of them consist of information about patient, disease, occupation and employer. Some of countries have special occupational related classification systems for themselves and some of them apply international classification systems such as ICD-10. Finally, the process of registration system was different in countries. Because occupational diseases are often preventable, but not curable, it is necessary to all countries, to consider prevention and early detection of occupational diseases as the objectives of their registry systems. Also it is recommended that all countries reach an agreement about global characteristics of occupational disease registries. This enables country to compare their data at international levels.

Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

PubMed Central

Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

2016-01-01

Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced stages of Parkinson’s disease. PMID:27776130

Peripleural lung disease detection based on multi-slice CT images

NASA Astrophysics Data System (ADS)

Matsuhiro, M.; Suzuki, H.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

2015-03-01

With the development of multi-slice CT technology, obtaining accurate 3D images of lung field in a short time become possible. To support that, a lot of image processing methods need to be developed. Detection peripleural lung disease is difficult due to its existence out of lung region, because lung extraction is often performed based on threshold processing. The proposed method uses thoracic inner region extracted by inner cavity of bone as well as air region, covers peripleural lung diseased cases such as lung nodule, calcification, pleural effusion and pleural plaque. We applied this method to 50 cases including 39 peripleural lung diseased cases. This method was able to detect 39 peripleural lung disease with 2.9 false positive per case.

Neuroinflammation in the pathogenesis of Alzheimer's disease. A rational framework for the search of novel therapeutic approaches.

PubMed

Morales, Inelia; Guzmán-Martínez, Leonardo; Cerda-Troncoso, Cristóbal; Farías, Gonzalo A; Maccioni, Ricardo B

2014-01-01

Alzheimer disease (AD) is the most common cause of dementia in people over 60 years old. The molecular and cellular alterations that trigger this disease are still diffuse, one of the reasons for the delay in finding an effective treatment. In the search for new targets to search for novel therapeutic avenues, clinical studies in patients who used anti-inflammatory drugs indicating a lower incidence of AD have been of value to support the neuroinflammatory hypothesis of the neurodegenerative processes and the role of innate immunity in this disease. Neuroinflammation appears to occur as a consequence of a series of damage signals, including trauma, infection, oxidative agents, redox iron, oligomers of τ and β-amyloid, etc. In this context, our theory of Neuroimmunomodulation focus on the link between neuronal damage and brain inflammatory process, mediated by the progressive activation of astrocytes and microglial cells with the consequent overproduction of proinflammatory agents. Here, we discuss about the role of microglial and astrocytic cells, the principal agents in neuroinflammation process, in the development of neurodegenerative diseases such as AD. In this context, we also evaluated the potential relevance of natural anti-inflammatory components, which include curcumin and the novel Andean Compound, as agents for AD prevention and as a coadjuvant for AD treatments.

Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches

PubMed Central

Morales, Inelia; Guzmán-Martínez, Leonardo; Cerda-Troncoso, Cristóbal; Farías, Gonzalo A.; Maccioni, Ricardo B.

2014-01-01

Alzheimer disease (AD) is the most common cause of dementia in people over 60 years old. The molecular and cellular alterations that trigger this disease are still diffuse, one of the reasons for the delay in finding an effective treatment. In the search for new targets to search for novel therapeutic avenues, clinical studies in patients who used anti-inflammatory drugs indicating a lower incidence of AD have been of value to support the neuroinflammatory hypothesis of the neurodegenerative processes and the role of innate immunity in this disease. Neuroinflammation appears to occur as a consequence of a series of damage signals, including trauma, infection, oxidative agents, redox iron, oligomers of τ and β-amyloid, etc. In this context, our theory of Neuroimmunomodulation focus on the link between neuronal damage and brain inflammatory process, mediated by the progressive activation of astrocytes and microglial cells with the consequent overproduction of proinflammatory agents. Here, we discuss about the role of microglial and astrocytic cells, the principal agents in neuroinflammation process, in the development of neurodegenerative diseases such as AD. In this context, we also evaluated the potential relevance of natural anti-inflammatory components, which include curcumin and the novel Andean Compound, as agents for AD prevention and as a coadjuvant for AD treatments. PMID:24795567

Effect of liberibacter infection (huanglongbing disease) of citrus on orange fruit physiology and fruit/fruit juice quality: chemical and physical analyses.

PubMed

Baldwin, Elizabeth; Plotto, Anne; Manthey, John; McCollum, Greg; Bai, Jinhe; Irey, Mike; Cameron, Randall; Luzio, Gary

2010-01-27

More than 90% of oranges in Florida are processed, and since Huanglongbing (HLB) disease has been rumored to affect fruit flavor, chemical and physical analyses were conducted on fruit and juice from healthy (Las -) and diseased (Las +) trees on three juice processing varieties over two seasons, and in some cases several harvests. Fruit, both asymptomatic and symptomatic for the disease, were used, and fresh squeezed and processed/pasteurized juices were evaluated. Fruit and juice characteristics measured included color, size, solids, acids, sugars, aroma volatiles, ascorbic acid, secondary metabolites, pectin, pectin-demethylating enzymes, and juice cloud. Results showed that asymptomatic fruit from symptomatic trees were similar to healthy fruit for many of the quality factors measured, but that juice from asymptomatic and especially symptomatic fruits were often higher in the bitter compounds limonin and nomilin. However, values were generally below reported taste threshold levels, and only symptomatic fruit seemed likely to cause flavor problems. There was variation due to harvest date, which was often greater than that due to disease. It is likely that the detrimental flavor attributes of symptomatic fruit (which often drop off the tree) will be largely diluted in commercial juice blends that include juice from fruit of several varieties, locations, and seasons.

A Descriptive Survey of Inflammatory Bowel Disease within the Active Army Population (1971-1982).

DTIC Science & Technology

1985-06-01

psychological response to stress has an impact on the disease once it is established. This includes the recurrence of the disease as well as its severity. An...underlying question that remains is: Which is the causal agent, the disease or the psychological response to the disease? The inflammatory process of the... psychological factor. Only with increased knowledge of their epidemiologic factors will researchers begin to understand the basis for these devastating

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

PubMed

Baillie, J Kenneth; Bretherick, Andrew; Haley, Christopher S; Clohisey, Sara; Gray, Alan; Neyton, Lucile P A; Barrett, Jeffrey; Stahl, Eli A; Tenesa, Albert; Andersson, Robin; Brown, J Ben; Faulkner, Geoffrey J; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Itoh, Masayoshi; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Mole, Damian; Bajic, Vladimir B; Heutink, Peter; Rehli, Michael; Kawaji, Hideya; Sandelin, Albin; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A; Hacohen, Nir; Freeman, Thomas C; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Hume, David A

2018-03-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn's disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits.

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease

PubMed Central

Gray, Alan; Neyton, Lucile P. A.; Barrett, Jeffrey; Stahl, Eli A.; Tenesa, Albert; Andersson, Robin; Brown, J. Ben; Faulkner, Geoffrey J.; Lizio, Marina; Schaefer, Ulf; Daub, Carsten; Kondo, Naoto; Lassmann, Timo; Kawai, Jun; Kawaji, Hideya; Suzuki, Harukazu; Satsangi, Jack; Wells, Christine A.; Hacohen, Nir; Freeman, Thomas C.; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Hume, David A.

2018-01-01

Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA). For most traits studied, phenotype-associated variants in regulatory regions were linked to tightly-coexpressed networks that are likely to share important functional characteristics. Coexpression provides a new signal, independent of phenotype association, to enable fine mapping of causative variants. The NDA coexpression approach identifies new genetic variants associated with specific traits, including an association between the regulation of the OCT1 cation transporter and genetic variants underlying circulating cholesterol levels. NDA strongly implicates particular cell types and tissues in disease pathogenesis. For example, distinct groupings of disease-associated regulatory regions implicate two distinct biological processes in the pathogenesis of ulcerative colitis; a further two separate processes are implicated in Crohn’s disease. Thus, our functional analysis of genetic predisposition to disease defines new distinct disease endotypes. We predict that patients with a preponderance of susceptibility variants in each group are likely to respond differently to pharmacological therapy. Together, these findings enable a deeper biological understanding of the causal basis of complex traits. PMID:29494619

BIOMONITORING OF REACTIVE OXYGEN SPECIES IN BIOLOGICAL FLUIDS

EPA Science Inventory

Elevated levels of reactive oxygen species (ROS) are associated with several disease processes in humans, including cancer, asthma, diabetes, and cardiac disease. We have explored whether ROS can be measured directly in human fluids, and their value as a biomarker of exposure an...

An approach to and web-based tool for infectious disease outbreak intervention analysis

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

Daughton, Ashlynn R.; Generous, Nicholas; Priedhorsky, Reid

Infectious diseases are a leading cause of death globally. Decisions surrounding how to control an infectious disease outbreak currently rely on a subjective process involving surveillance and expert opinion. However, there are many situations where neither may be available. Modeling can fill gaps in the decision making process by using available data to provide quantitative estimates of outbreak trajectories. Effective reduction of the spread of infectious diseases can be achieved through collaboration between the modeling community and public health policy community. However, such collaboration is rare, resulting in a lack of models that meet the needs of the public healthmore » community. Here we show a Susceptible-Infectious-Recovered (SIR) model modified to include control measures that allows parameter ranges, rather than parameter point estimates, and includes a web user interface for broad adoption. We apply the model to three diseases, measles, norovirus and influenza, to show the feasibility of its use and describe a research agenda to further promote interactions between decision makers and the modeling community.« less

An approach to and web-based tool for infectious disease outbreak intervention analysis

DOE PAGES

Daughton, Ashlynn R.; Generous, Nicholas; Priedhorsky, Reid; ...

2017-04-18

Infectious diseases are a leading cause of death globally. Decisions surrounding how to control an infectious disease outbreak currently rely on a subjective process involving surveillance and expert opinion. However, there are many situations where neither may be available. Modeling can fill gaps in the decision making process by using available data to provide quantitative estimates of outbreak trajectories. Effective reduction of the spread of infectious diseases can be achieved through collaboration between the modeling community and public health policy community. However, such collaboration is rare, resulting in a lack of models that meet the needs of the public healthmore » community. Here we show a Susceptible-Infectious-Recovered (SIR) model modified to include control measures that allows parameter ranges, rather than parameter point estimates, and includes a web user interface for broad adoption. We apply the model to three diseases, measles, norovirus and influenza, to show the feasibility of its use and describe a research agenda to further promote interactions between decision makers and the modeling community.« less

Modelling the impacts of pests and diseases on agricultural systems.

PubMed

Donatelli, M; Magarey, R D; Bregaglio, S; Willocquet, L; Whish, J P M; Savary, S

2017-07-01

The improvement and application of pest and disease models to analyse and predict yield losses including those due to climate change is still a challenge for the scientific community. Applied modelling of crop diseases and pests has mostly targeted the development of support capabilities to schedule scouting or pesticide applications. There is a need for research to both broaden the scope and evaluate the capabilities of pest and disease models. Key research questions not only involve the assessment of the potential effects of climate change on known pathosystems, but also on new pathogens which could alter the (still incompletely documented) impacts of pests and diseases on agricultural systems. Yield loss data collected in various current environments may no longer represent a adequate reference to develop tactical, decision-oriented, models for plant diseases and pests and their impacts, because of the ongoing changes in climate patterns. Process-based agricultural simulation modelling, on the other hand, appears to represent a viable methodology to estimate the impacts of these potential effects. A new generation of tools based on state-of-the-art knowledge and technologies is needed to allow systems analysis including key processes and their dynamics over appropriate suitable range of environmental variables. This paper offers a brief overview of the current state of development in coupling pest and disease models to crop models, and discusses technical and scientific challenges. We propose a five-stage roadmap to improve the simulation of the impacts caused by plant diseases and pests; i) improve the quality and availability of data for model inputs; ii) improve the quality and availability of data for model evaluation; iii) improve the integration with crop models; iv) improve the processes for model evaluation; and v) develop a community of plant pest and disease modelers.

Advances of Molecular Imaging for Monitoring the Anatomical and Functional Architecture of the Olfactory System.

PubMed

Zhang, Xintong; Bi, Anyao; Gao, Quansheng; Zhang, Shuai; Huang, Kunzhu; Liu, Zhiguo; Gao, Tang; Zeng, Wenbin

2016-01-20

The olfactory system of organisms serves as a genetically and anatomically model for studying how sensory input can be translated into behavior output. Some neurologic diseases are considered to be related to olfactory disturbance, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis, and so forth. However, it is still unclear how the olfactory system affects disease generation processes and olfaction delivery processes. Molecular imaging, a modern multidisciplinary technology, can provide valid tools for the early detection and characterization of diseases, evaluation of treatment, and study of biological processes in living subjects, since molecular imaging applies specific molecular probes as a novel approach to produce special data to study biological processes in cellular and subcellular levels. Recently, molecular imaging plays a key role in studying the activation of olfactory system, thus it could help to prevent or delay some diseases. Herein, we present a comprehensive review on the research progress of the imaging probes for visualizing olfactory system, which is classified on different imaging modalities, including PET, MRI, and optical imaging. Additionally, the probes' design, sensing mechanism, and biological application are discussed. Finally, we provide an outlook for future studies in this field.

Addison's disease secondary to connective tissue diseases: a report of six cases.

PubMed

Zhang, Zhuo-li; Wang, Yu; Zhou, Wei; Hao, Yan-jie

2009-04-01

Addison's disease is an autoimmune process. However, Addison's disease associated with connective tissue diseases (CTD) is only occasionally reported. Here, we report six cases of Addison's disease secondary to a variety of CTD, which include systemic lupus erythematosus, Takayasu arteritis, systemic sclerosis, ankylosing spondylitis (AS) and antiphospholipid antibody syndrome. The association of Addison's disease with Takayasu arteritis and AS is reported for the first time. We also found high prevalence of hypothyroidism as concomitant autoimmune disorder. Our case series highlight the autoimmune features of Addison's disease. Therefore, we suggest considering adrenal dysfunction in patients with CTD.

Detection and measurement of plant disease symptoms using visible-wavelength photography and image analysis

USDA-ARS?s Scientific Manuscript database

Disease assessment is required for many purposes including predicting yield loss, monitoring and forecasting epidemics, judging host resistance, and for studying fundamental biological host-pathogen processes. Inaccurate and/or imprecise assessments can result in incorrect conclusions or actions. Im...

Miscellaneous bacterial diseases

USGS Publications Warehouse

Friend, M.

1999-01-01

Disease in free-ranging birds is caused by many other pathogenic bacteria in addition to those illustrated within this section. These other diseases are currently considered less important because of their infrequent occurrence, the small numbers of birds generally lost annually, or because they primarily result from infection by opportunistic pathogens and they require concurrent disease processes for them to become apparent. The following brief highlights about the more important of these diseases are included to acquaint readers with their existence and provide some basic information about their ecology.

Mitochondrial medicine for neurodegenerative diseases.

PubMed

Du, Heng; Yan, Shirley ShiDu

2010-05-01

Mitochondrial dysfunction has been reported in a wide array of neurological disorders ranging from neuromuscular to neurodegenerative diseases. Recent studies on neurodegenerative diseases have revealed that mitochondrial pathology is generally found in inherited or sporadic neurodegenerative diseases and is believed to be involved in the pathophysiological process of these diseases. Commonly seen types of mitochondrial dysfunction in neurodegenerative diseases include excessive free radical generation, lowered ATP production, mitochondrial permeability transition, mitochondrial DNA lesions, perturbed mitochondrial dynamics and apoptosis. Mitochondrial medicine as an emerging therapeutic strategy targeted to mitochondrial dysfunction in neurodegenerative diseases has been proven to be of value, though this area of research is still at in its early stage. In this article, we report on recent progress in the development of several mitochondrial therapies including antioxidants, blockade of mitochondrial permeability transition, and mitochondrial gene therapy as evidence that mitochondrial medicine has promise in the treatment of neurodegenerative diseases. 2010 Elsevier Ltd. All rights reserved.

Goal-setting in clinical medicine.

PubMed

Bradley, E H; Bogardus, S T; Tinetti, M E; Inouye, S K

1999-07-01

The process of setting goals for medical care in the context of chronic disease has received little attention in the medical literature, despite the importance of goal-setting in the achievement of desired outcomes. Using qualitative research methods, this paper develops a theory of goal-setting in the care of patients with dementia. The theory posits several propositions. First, goals are generated from embedded values but are distinct from values. Goals vary based on specific circumstances and alternatives whereas values are person-specific and relatively stable in the face of changing circumstances. Second, goals are hierarchical in nature, with complex mappings between general and specific goals. Third, there are a number of factors that modify the goal-setting process, by affecting the generation of goals from values or the translation of general goals to specific goals. Modifying factors related to individuals include their degree of risk-taking, perceived self-efficacy, and acceptance of the disease. Disease factors that modify the goal-setting process include the urgency and irreversibility of the medical condition. Pertinent characteristics of the patient-family-clinician interaction include the level of participation, control, and trust among patients, family members, and clinicians. The research suggests that the goal-setting process in clinical medicine is complex, and the potential for disagreements regarding goals substantial. The nature of the goal-setting process suggests that explicit discussion of goals for care may be necessary to promote effective patient-family-clinician communication and adequate care planning.

The role of heat shock proteins in kidney disease

PubMed Central

2016-01-01

Abstract Heat Shock Proteins (HSP) belong to the family of intracellular proteins that are constitutively expressed and are upregulated by various stressors including heat, oxidative and chemical stress. HSP helps in reparative processes, including the refolding of damaged proteins and the removal of irreparably damaged proteins that would initiate cellular death or apoptosis. A growing body of evidence has expanded the role of HSP and defined their role in diseases such as neurodegenerative disorders, cancer, ischemic heart disease and kidney diseases. The protective role of HSP in ischemic renal injury has been described and HSP impairment has been noted in other forms of kidney injuries including post-transplant situation. Further research into the role of HSP in prevention of kidney injury is crucial if translation from the laboratory to patient bedside has to occur. This article aims to be a review of heat shock protein, and its relevance to kidney diseases. PMID:28191532

Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease

PubMed Central

Rouault, Tracey A.

2012-01-01

Iron-sulfur (Fe-S) clusters are ubiquitous cofactors composed of iron and inorganic sulfur. They are required for the function of proteins involved in a wide range of activities, including electron transport in respiratory chain complexes, regulatory sensing, photosynthesis and DNA repair. The proteins involved in the biogenesis of Fe-S clusters are evolutionarily conserved from bacteria to humans, and many insights into the process of Fe-S cluster biogenesis have come from studies of model organisms, including bacteria, fungi and plants. It is now clear that several rare and seemingly dissimilar human diseases are attributable to defects in the basic process of Fe-S cluster biogenesis. Although these diseases –which include Friedreich’s ataxia (FRDA), ISCU myopathy, a rare form of sideroblastic anemia, an encephalomyopathy caused by dysfunction of respiratory chain complex I and multiple mitochondrial dysfunctions syndrome – affect different tissues, a feature common to many of them is that mitochondrial iron overload develops as a secondary consequence of a defect in Fe-S cluster biogenesis. This Commentary outlines the basic steps of Fe-S cluster biogenesis as they have been defined in model organisms. In addition, it draws attention to refinements of the process that might be specific to the subcellular compartmentalization of Fe-S cluster biogenesis proteins in some eukaryotes, including mammals. Finally, it outlines several important unresolved questions in the field that, once addressed, should offer important clues into how mitochondrial iron homeostasis is regulated, and how dysfunction in Fe-S cluster biogenesis can contribute to disease. PMID:22382365

AgMIP: Next Generation Models and Assessments

NASA Astrophysics Data System (ADS)

Rosenzweig, C.

2014-12-01

Next steps in developing next-generation crop models fall into several categories: significant improvements in simulation of important crop processes and responses to stress; extension from simplified crop models to complex cropping systems models; and scaling up from site-based models to landscape, national, continental, and global scales. Crop processes that require major leaps in understanding and simulation in order to narrow uncertainties around how crops will respond to changing atmospheric conditions include genetics; carbon, temperature, water, and nitrogen; ozone; and nutrition. The field of crop modeling has been built on a single crop-by-crop approach. It is now time to create a new paradigm, moving from 'crop' to 'cropping system.' A first step is to set up the simulation technology so that modelers can rapidly incorporate multiple crops within fields, and multiple crops over time. Then the response of these more complex cropping systems can be tested under different sustainable intensification management strategies utilizing the updated simulation environments. Model improvements for diseases, pests, and weeds include developing process-based models for important diseases, frameworks for coupling air-borne diseases to crop models, gathering significantly more data on crop impacts, and enabling the evaluation of pest management strategies. Most smallholder farming in the world involves integrated crop-livestock systems that cannot be represented by crop modeling alone. Thus, next-generation cropping system models need to include key linkages to livestock. Livestock linkages to be incorporated include growth and productivity models for grasslands and rangelands as well as the usual annual crops. There are several approaches for scaling up, including use of gridded models and development of simpler quasi-empirical models for landscape-scale analysis. On the assessment side, AgMIP is leading a community process for coordinated contributions to IPCC AR6 that involves the key modeling groups from around the world including North America, Europe, South America, Sub-Saharan Africa, South Asia, East Asia, and Australia and Oceania. This community process will lead to mutually agreed protocols for coordinated global and regional assessments.

Text-based Analytics for Biosurveillance

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

Charles, Lauren E.; Smith, William P.; Rounds, Jeremiah

The ability to prevent, mitigate, or control a biological threat depends on how quickly the threat is identified and characterized. Ensuring the timely delivery of data and analytics is an essential aspect of providing adequate situational awareness in the face of a disease outbreak. This chapter outlines an analytic pipeline for supporting an advanced early warning system that can integrate multiple data sources and provide situational awareness of potential and occurring disease situations. The pipeline, includes real-time automated data analysis founded on natural language processing (NLP), semantic concept matching, and machine learning techniques, to enrich content with metadata related tomore » biosurveillance. Online news articles are presented as an example use case for the pipeline, but the processes can be generalized to any textual data. In this chapter, the mechanics of a streaming pipeline are briefly discussed as well as the major steps required to provide targeted situational awareness. The text-based analytic pipeline includes various processing steps as well as identifying article relevance to biosurveillance (e.g., relevance algorithm) and article feature extraction (who, what, where, why, how, and when). The ability to prevent, mitigate, or control a biological threat depends on how quickly the threat is identified and characterized. Ensuring the timely delivery of data and analytics is an essential aspect of providing adequate situational awareness in the face of a disease outbreak. This chapter outlines an analytic pipeline for supporting an advanced early warning system that can integrate multiple data sources and provide situational awareness of potential and occurring disease situations. The pipeline, includes real-time automated data analysis founded on natural language processing (NLP), semantic concept matching, and machine learning techniques, to enrich content with metadata related to biosurveillance. Online news articles are presented as an example use case for the pipeline, but the processes can be generalized to any textual data. In this chapter, the mechanics of a streaming pipeline are briefly discussed as well as the major steps required to provide targeted situational awareness. The text-based analytic pipeline includes various processing steps as well as identifying article relevance to biosurveillance (e.g., relevance algorithm) and article feature extraction (who, what, where, why, how, and when).« less

Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging.

PubMed

Podtelezhnikov, Alexei A; Tanis, Keith Q; Nebozhyn, Michael; Ray, William J; Stone, David J; Loboda, Andrey P

2011-01-01

Alzheimer's disease (AD) is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age), Alz (Alzheimer), Inflame (inflammation), and NdStress (neurodegenerative stress). BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT) transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression. © 2011 Podtelezhnikov et al.

Molecular Insights into the Pathogenesis of Alzheimer's Disease and Its Relationship to Normal Aging

PubMed Central

Podtelezhnikov, Alexei A.; Tanis, Keith Q.; Nebozhyn, Michael; Ray, William J.

2011-01-01

Alzheimer's disease (AD) is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age), Alz (Alzheimer), Inflame (inflammation), and NdStress (neurodegenerative stress). BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT) transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression. PMID:22216330

Understanding interprofessional collaboration in the context of chronic disease management for older adults living in communities: a concept analysis.

PubMed

Bookey-Bassett, Sue; Markle-Reid, Maureen; Mckey, Colleen A; Akhtar-Danesh, Noori

2017-01-01

To report a concept analysis of interprofessional collaboration in the context of chronic disease management, for older adults living in communities. Increasing prevalence of chronic disease among older adults is creating significant burden for patients, families and healthcare systems. Managing chronic disease for older adults living in the community requires interprofessional collaboration across different health and other care providers, organizations and sectors. However, there is a lack of consensus about the definition and use of interprofessional collaboration for community-based chronic disease management. Concept analysis. Electronic databases CINAHL, Medline, HealthStar, EMBASE, PsychINFO, Ageline and Cochrane Database were searched from 2000 - 2013. Rodgers' evolutionary method for concept analysis. The most common surrogate term was interdisciplinary collaboration. Related terms were interprofessional team, multidisciplinary team and teamwork. Attributes included: an evolving interpersonal process; shared goals, decision-making and care planning; interdependence; effective and frequent communication; evaluation of team processes; involving older adults and family members in the team; and diverse and flexible team membership. Antecedents comprised: role awareness; interprofessional education; trust between team members; belief that interprofessional collaboration improves care; and organizational support. Consequences included impacts on team composition and function, care planning processes and providers' knowledge, confidence and job satisfaction. Interprofessional collaboration is a complex evolving concept. Key components of interprofessional collaboration in chronic disease management for community-living older adults are identified. Implications for nursing practice, education and research are proposed. © 2016 John Wiley & Sons Ltd.

Chronic pain and pain processing in Parkinson's disease.

PubMed

Blanchet, Pierre J; Brefel-Courbon, Christine

2017-10-12

Pain is experienced by the vast majority of patients living with Parkinson's disease. It is most often of nociceptive origin, but may also be ascribed to neuropathic (radicular or central) or miscellaneous sources. The recently validated King's Parkinson's Disease Pain Scale is based on 7 domains including musculoskeletal pain, chronic body pain (central or visceral), fluctuation-related pain, nocturnal pain, oro-facial pain, pain with discolouration/oedema/swelling, and radicular pain. The basal ganglia integrate incoming nociceptive information and contribute to coordinated motor responses in pain avoidance and nocifensive behaviors. In Parkinson's disease, nigral and extra-nigral pathology, involving cortical areas, brainstem nuclei, and spinal cord, may contribute to abnormal central nociceptive processing in patients experiencing pain or not. The dopamine deficit lowers multimodal pain thresholds that are amenable to correction following levodopa dosing. Functional brain imaging with positron emission tomography following administration of H 2 15 O revealed abnormalities in the sensory discriminative processing of pain (insula/SII), as well as in the affective motivational processing of pain (anterior cingulate cortex, prefrontal cortex). Pain management is dependent on efforts invested in diagnostic accuracy to distinguish nociceptive from neuropathic pain. Treatment requires an integrated approach including strategies to lessen levodopa-related response fluctuations, in addition to other pharmacological and non-pharmacological options such as deep brain stimulation and rehabilitation. Copyright © 2017. Published by Elsevier Inc.

[Clinical and etiopathogenetic role of plasminogen and metaloproteinase systems in the tumor growth. Pericellular proteolysis of extracellular matrix and tumor growth].

PubMed

Cosić, Sanda Jelisavac; Kovac, Zdenko

2011-01-01

Pericellular proteolysis is a cascade process involved in degradation of extracellular matrix. This process is included in various physiological and pathological processes. Pericellullar proteolysis has major functions like degradation of tissue stroma and weakening of intercellular connections but it also has a function in the synthesis of bioactive molecules (cytokines, growth factors and inhibitory factors). Plasminogen system is involved in fibrinolysis and starts metalloproteinase activation. Activity of proteolytic molecules is controlled by the rate of zymogenic activation, half-life of molecules, and action of inhibitory molecules. Inhibition is achieved through direct binding of inhibitor and enzyme and takes a few steps. Pericellular proteolysis is involved in tumor invasion and metastasis, inflammatory reaction, degenerative diseases and other diseases. Pathophysiological regulation of pericellular proteolysis in mentioned diseases contributes to clinical properties of diseases and has diagnostic and therapeutic importance.

The Function of V-ATPases in Cancer

PubMed Central

Stransky, Laura; Cotter, Kristina

2016-01-01

The vacuolar ATPases (V-ATPases) are a family of proton pumps that couple ATP hydrolysis to proton transport into intracellular compartments and across the plasma membrane. They function in a wide array of normal cellular processes, including membrane traffic, protein processing and degradation, and the coupled transport of small molecules, as well as such physiological processes as urinary acidification and bone resorption. The V-ATPases have also been implicated in a number of disease processes, including viral infection, renal disease, and bone resorption defects. This review is focused on the growing evidence for the important role of V-ATPases in cancer. This includes functions in cellular signaling (particularly Wnt, Notch, and mTOR signaling), cancer cell survival in the highly acidic environment of tumors, aiding the development of drug resistance, as well as crucial roles in tumor cell invasion, migration, and metastasis. Of greatest excitement is evidence that at least some tumors express isoforms of V-ATPase subunits whose disruption is not lethal, leading to the possibility of developing anti-cancer therapeutics that selectively target V-ATPases that function in cancer cells. PMID:27335445

Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative.

PubMed

Baillet, Athan; Gossec, Laure; Carmona, Loreto; Wit, Maarten de; van Eijk-Hustings, Yvonne; Bertheussen, Heidi; Alison, Kent; Toft, Mette; Kouloumas, Marios; Ferreira, Ricardo J O; Oliver, Susan; Rubbert-Roth, Andrea; van Assen, Sander; Dixon, William G; Finckh, Axel; Zink, Angela; Kremer, Joel; Kvien, Tore K; Nurmohamed, Michael; van der Heijde, Desirée; Dougados, Maxime

2016-06-01

In chronic inflammatory rheumatic diseases, comorbidities such as cardiovascular diseases and infections are suboptimally prevented, screened for and managed. The objective of this European League Against Rheumatism (EULAR) initiative was to propose points to consider to collect comorbidities in patients with chronic inflammatory rheumatic diseases. We also aimed to develop a pragmatic reporting form to foster the implementation of the points to consider. In accordance with the EULAR Standardised Operating Procedures, the process comprised (1) a systematic literature review of existing recommendations on reporting, screening for or preventing six selected comorbidities: ischaemic cardiovascular diseases, malignancies, infections, gastrointestinal diseases, osteoporosis and depression and (2) a consensus process involving 21 experts (ie, rheumatologists, patients, health professionals). Recommendations on how to treat the comorbidities were not included in the document as they vary across countries. The literature review retrieved 42 articles, most of which were recommendations for reporting or screening for comorbidities in the general population. The consensus process led to three overarching principles and 15 points to consider, related to the six comorbidities, with three sections: (1) reporting (ie, occurrence of the comorbidity and current treatments); (2) screening for disease (eg, mammography) or for risk factors (eg, smoking) and (3) prevention (eg, vaccination). A reporting form (93 questions) corresponding to a practical application of the points to consider was developed. Using an evidence-based approach followed by expert consensus, this EULAR initiative aims to improve the reporting and prevention of comorbidities in chronic inflammatory rheumatic diseases. Next steps include dissemination and implementation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Tachykinins and Their Receptors: Contributions to Physiological Control and the Mechanisms of Disease

PubMed Central

Steinhoff, Martin S.; von Mentzer, Bengt; Geppetti, Pierangelo; Pothoulakis, Charalabos; Bunnett, Nigel W.

2014-01-01

The tachykinins, exemplified by substance P, are one of the most intensively studied neuropeptide families. They comprise a series of structurally related peptides that derive from alternate processing of three Tac genes and are expressed throughout the nervous and immune systems. Tachykinins interact with three neurokinin G protein-coupled receptors. The signaling, trafficking, and regulation of neurokinin receptors have also been topics of intense study. Tachykinins participate in important physiological processes in the nervous, immune, gastrointestinal, respiratory, urogenital, and dermal systems, including inflammation, nociception, smooth muscle contractility, epithelial secretion, and proliferation. They contribute to multiple diseases processes, including acute and chronic inflammation and pain, fibrosis, affective and addictive disorders, functional disorders of the intestine and urinary bladder, infection, and cancer. Neurokinin receptor antagonists are selective, potent, and show efficacy in models of disease. In clinical trials there is a singular success: neurokinin 1 receptor antagonists to treat nausea and vomiting. New information about the involvement of tachykinins in infection, fibrosis, and pruritus justifies further trials. A deeper understanding of disease mechanisms is required for the development of more predictive experimental models, and for the design and interpretation of clinical trials. Knowledge of neurokinin receptor structure, and the development of targeting strategies to disrupt disease-relevant subcellular signaling of neurokinin receptors, may refine the next generation of neurokinin receptor antagonists. PMID:24382888

Omics analysis of mouse brain models of human diseases.

PubMed

Paban, Véronique; Loriod, Béatrice; Villard, Claude; Buee, Luc; Blum, David; Pietropaolo, Susanna; Cho, Yoon H; Gory-Faure, Sylvie; Mansour, Elodie; Gharbi, Ali; Alescio-Lautier, Béatrice

2017-02-05

The identification of common gene/protein profiles related to brain alterations, if they exist, may indicate the convergence of the pathogenic mechanisms driving brain disorders. Six genetically engineered mouse lines modelling neurodegenerative diseases and neuropsychiatric disorders were considered. Omics approaches, including transcriptomic and proteomic methods, were used. The gene/protein lists were used for inter-disease comparisons and further functional and network investigations. When the inter-disease comparison was performed using the gene symbol identifiers, the number of genes/proteins involved in multiple diseases decreased rapidly. Thus, no genes/proteins were shared by all 6 mouse models. Only one gene/protein (Gfap) was shared among 4 disorders, providing strong evidence that a common molecular signature does not exist among brain diseases. The inter-disease comparison of functional processes showed the involvement of a few major biological processes indicating that brain diseases of diverse aetiologies might utilize common biological pathways in the nervous system, without necessarily involving similar molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Post-approval Studies for Rare Disease Treatments and Orphan Drugs.

PubMed

Maier, William C; Christensen, Ronald A; Anderson, Patricia

2017-01-01

Drug development involves a multi-stage process of drug discovery, animal studies and human clinical trials to assess the safety and efficacy of new medications. Rare disease drug development involves a much smaller number of affected patients, a predominance of pediatric patients and more complicated disease presentation. Post-approval studies are designed to address several limitations associated with the rare disease clinical trials.National and international regulatory agencies in the US and Europe have adopted similar approaches to requirements post-approval data for rare diseases and orphan drug indications. The US FDA published guidance in 2011 and the European Medicines Agency in 2015.Post-approval studies for rare diseases include observational studies, pragmatic trials and randomized controlled studies. Observational studies include both original data collection studies and the use of secondary data (retrospective studies). Original data collection can address limitations of retrospective studies resulting from incomplete information in secondary data sources. Disease registries focus on detail about a broad range of patients with a rare disease while product-related registries focus on specific health care outcomes associated with a single product and may incorporate a comparator of an alternative therapy or therapies.Rare disease patients can be difficult to find and enroll in a registry using conventional physician based driven recruitment. The study process also needs to recognize changes in the patient's disease and lifestyle and adapt both the study design and methods over time. Many rare diseases have strong patient advocacy groups that can in aid the design and execution of rare disease registries.

Pericytes of the neurovascular unit: Key functions and signaling pathways

PubMed Central

Sweeney, Melanie D.; Ayyadurai, Shiva; Zlokovic, Berislav V.

2017-01-01

Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles, and post-capillary venules. The central nervous system (CNS) pericytes are uniquely positioned within the neurovascular unit between endothelial cells, astrocytes, and neurons. They integrate, coordinate, and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease including regulation of the blood-brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation, and stem cell activity. Here, we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes, and neurons that control neurovascular functions. We also review the role of pericytes in different CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies. PMID:27227366

Complex Relationships Between Food, Diet, and the Microbiome.

PubMed

Pace, Laura A; Crowe, Sheila E

2016-06-01

Diet is a risk factor in several medically important disease states, including obesity, celiac disease, and functional gastrointestinal disorders. Modification of diet can prevent, treat, or alleviate some of the symptoms associated with these diseases and improve general health. It is important to provide patients with simple dietary recommendations to increase the probability of successful implementation. These recommendations include increasing vegetable, fruit, and fiber intake, consuming lean protein sources to enhance satiety, avoiding or severely limiting highly processed foods, and reducing portion sizes for overweight and obese patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Autism, Asthma, Inflammation, and the Hygiene Hypothesis

PubMed Central

Becker, Kevin G.

2007-01-01

Inflammation and the genes, molecules, and biological pathways that lead to inflammatory processes influence many important and disparate biological processes and disease states that are quite often not generally considered classical inflammatory or autoimmune disorders. These include development, reproduction, aging, tumor development and tumor rejection, cardiovascular pathologies, metabolic disorders, as well as neurological and psychiatric disorders. This paper compares parallel aspects of autism and inflammatory disorders with an emphasis on asthma. These comparisons include epidemiological, morphometric, molecular, and genetic aspects of both disease types, contributing to a hypothesis of autism in the context of the immune based hygiene hypothesis. This hypothesis is meant to address the apparent rise in the prevalence of autism in the population. PMID:17412520

Autism, asthma, inflammation, and the hygiene hypothesis.

PubMed

Becker, Kevin G

2007-01-01

Inflammation and the genes, molecules, and biological pathways that lead to inflammatory processes influence many important and disparate biological processes and disease states that are quite often not generally considered classical inflammatory or autoimmune disorders. These include development, reproduction, aging, tumor development and tumor rejection, cardiovascular pathologies, metabolic disorders, as well as neurological and psychiatric disorders. This paper compares parallel aspects of autism and inflammatory disorders with an emphasis on asthma. These comparisons include epidemiological, morphometric, molecular, and genetic aspects of both disease types, contributing to a hypothesis of autism in the context of the immune based hygiene hypothesis. This hypothesis is meant to address the apparent rise in the prevalence of autism in the population.

[Fibrous tissue(s): a key for lesion characterization in digestive diseases].

PubMed

Régent, D; Laurent, V; Antunes, L; Debelle, L; Cannard, L; Leclerc, Jc; Beot, S

2002-02-01

Fibrosis is one of the hallmarks of inflammatory and repair processes in pathology. Various exogenous and endogenous stimuli, including tumor development, can induce inflammatory reactions. During the post-equilibrium phase after IV injection of non specific contrast media, CT and/or MR allow the study of these inflammatory answers to tumoral or infectious processes. Delayed enhancement of collagenic fibrous tissue during the late post-equilibrium phase is an essential complementary data in the characterization of many liver lesions: cirrhosis, cholangiocarcinoma, focal nodular hyperplasia, fibrous metastasis. but also for the differential diagnosis of pancreatic diseases (groove pancreatitis vs ductal adenocarcinoma) or of gastro-intestinal diseases (gastric adenocarcinoma vs lymphoma, mechanical complication vs inflammatory bouts of ileal Crohn's disease).

Role of Experience and Context in Learning To Diagnose Lyme Disease.

ERIC Educational Resources Information Center

Bakken, Lori L.

2002-01-01

Using grounded theory, the learning processes used by nine physicians to diagnose Lyme Disease were investigated. Repetition and counterexperiences served to frame the problem along a continuum of familiarity. Results suggest ways to prepare case studies that include variety, repetition, and counterexperiences to teach diagnosis. (Contains 28…

A retrospective study of disease in elasmobranchs.

PubMed

Garner, M M

2013-05-01

This report reviews diseases of 1546 elasmobranchs representing at least 60 species submitted to Northwest ZooPath from 1994 to 2010. Cownose rays (Rhinoptera bonasus) (78), southern rays (Dasyatis americana) (75), dusky smooth-hounds (Mustelus canis) (74), bonnethead sharks (Sphyrna tiburo) (66), and bamboo sharks (Hemiscylliidae) (56) were the most commonly submitted species. Infectious/inflammatory disease was most common (33.5%) followed by nutritional (11.9%, mostly emaciation), traumatic (11.3%), cardiovascular (5.5%, mostly shock), and toxin-associated disease (3.7%). Bacterial infections (518/1546, 15%) included sepsis (136/518, 26%), dermatitis (7%), branchitis (6%), and enteritis (4%). Fungal infections (10/1546, 0.6%) included dermatitis (30%), hepatitis (30%), and branchitis (20%). Viral or suspected viral infections or disease processes (15/1546, 1%) included papillomatosis (47%), herpesvirus (20%), and adenovirus (7%). Parasitic infections (137/1546, 9%) included nematodiasis (36/137, 26%), ciliate infections (23%), trematodiasis (20%), coccidiosis (6%), myxozoanosis (5%), amoebiasis (4%), cestodiasis (1%), and flagellate infections (1%). Inflammation of unknown cause (401/1546, 26%) included enteritis (55/401, 14%), branchitis (9%), encephalitis (9%), and dermatitis (7%). Traumatic diseases (174/1546, 11.3%) included skin trauma (103/174, 60%), stress/maladaptation (9%), and gut trauma (7%). Toxicoses (57/1546, 4%) included toxic gill disease (16/57, 26%), gas bubble disease (19%), fenbendazole (7%), ammonia (7%), chlorine (5%), and chloramine (3%). Species trends included visceral nematodiasis in black-nosed sharks (Carcharhinus acronotus) (55%); sepsis in dusky smooth-hounds (41%), blue-spotted stingrays (36%), southern rays (36%), and wobeggong sharks (Orectolobus spp) (69%); emaciation in bamboo (33%) and bonnethead (32%) sharks and freshwater stingrays (Potamotrygon motoro) (32%); and trauma in bonnethead sharks (30%).

Extracellular Matrix Degradation and Remodeling in Development and Disease

PubMed Central

Lu, Pengfei; Takai, Ken; Weaver, Valerie M.; Werb, Zena

2011-01-01

The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine. PMID:21917992

Mitochondrial Fission and Autophagy in the Normal and Diseased Heart

PubMed Central

Iglewski, Myriam; Hill, Joseph A.; Lavandero, Sergio; Rothermel, Beverly A.

2011-01-01

Sustained hypertension promotes structural, functional and metabolic remodeling of cardiomyocyte mitochondria. As long-lived, postmitotic cells, cardiomyocytes turn over mitochondria continuously to compensate for changes in energy demands and to remove damaged organelles. This process involves fusion and fission of existing mitochondria to generate new organelles and separate old ones for degradation via autophagy. Autophagy is a lysosome-dependent proteolytic pathway capable of processing cellular components, including organelles and protein aggregates. Autophagy can be either nonselective or selective and contributes to remodeling of the myocardium under stress. Fission of mitochondria, loss of membrane potential, and ubiquitination are emerging as critical steps that direct selective autophagic degradation of mitochondria. This review discusses the molecular mechanisms controlling mitochondrial dynamics, including fission, fusion, transport, and degradation. Furthermore, it examines recent studies revealing the importance of these processes in normal and diseased heart. PMID:20865352

Impact of age on markers of HIV-1 disease

PubMed Central

Pirrone, Vanessa; Libon, David J; Sell, Christian; Lerner, Chad A; Nonnemacher, Michael R; Wigdahl, Brian

2013-01-01

Aging is a complicated process characterized by a progressive loss of homeostasis, which results in an increased vulnerability to multiple diseases. HIV-1-infected patients demonstrate a premature aging phenotype and develop certain age-related diseases earlier in their lifespan than what is seen in the general population. Age-related comorbidities may include the development of bone disease, metabolic disorders, neurologic impairment and immunosenescence. Age also appears to have an effect on traditional markers of HIV-1 disease progression, including CD4+ T-cell count and viral load. These effects are not only a consequence of HIV-1 infection, but in many cases, are also linked to antiretroviral therapy. This review summarizes the complex interplay between HIV-1 infection and aging, and the impact that aging has on markers of HIV-1 disease. PMID:23596462

Vogt-Koyanagi-Harada disease.

PubMed

Burkholder, Bryn M

2015-11-01

The purpose of this article is to review the current literature on Vogt-Koyanagi-Harada (VKH) disease, including current treatment options and new research directions. Recent publications on VKH disease show an increased focus on the immunogenetics and immune pathways associated with the development of VKH disease. There have also been advances in imaging modalities and techniques that may help to better elucidate the disease process in eyes with VKH disease. VKH disease is an autoimmune, multisystem inflammatory disorder, the cause of which is still incompletely understood. Continued research may elucidate the causes and triggers of immune dysregulation in this disease, and in doing so, identify novel therapeutic targets.

Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

PubMed Central

Hanson, M. A.; Gluckman, P. D.

2014-01-01

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention. PMID:25287859

Involvement of the Warburg effect in non-tumor diseases processes.

PubMed

Chen, Zhe; Liu, Meiqing; Li, Lanfang; Chen, Linxi

2018-04-01

Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β-mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non-tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non-tumor diseases. © 2017 Wiley Periodicals, Inc.

Cortical Odor Processing in Health and Disease

PubMed Central

Wilson, Donald A.; Xu, Wenjin; Sadrian, Benjamin; Courtiol, Emmanuelle; Cohen, Yaniv; Barnes, Dylan C.

2014-01-01

The olfactory system has a rich cortical representation, including a large archicortical component present in most vertebrates, and in mammals neocortical components including the entorhinal and orbitofrontal cortices. Together, these cortical components contribute to normal odor perception and memory. They help transform the physicochemical features of volatile molecules inhaled or exhaled through the nose into the perception of odor objects with rich associative and hedonic aspects. This chapter focuses on how olfactory cortical areas contribute to odor perception and begins to explore why odor perception is so sensitive to disease and pathology. Odor perception is disrupted by a wide range of disorders including Alzheimer’s disease, Parkinson’s disease, schizophrenia, depression, autism, and early life exposure to toxins. This olfactory deficit often occurs despite maintained functioning in other sensory systems. Does the unusual network of olfactory cortical structures contribute to this sensitivity? PMID:24767487

Diet and Inflammation in Alzheimer's Disease and Related Chronic Diseases: A Review.

PubMed

Gardener, Samantha L; Rainey-Smith, Stephanie R; Martins, Ralph N

2016-01-01

Inflammation is one of the pathological features of the neurodegenerative disease, Alzheimer's disease (AD). A number of additional disorders are likewise associated with a state of chronic inflammation, including obesity, cardiovascular disease, and type-2 diabetes, which are themselves risk factors for AD. Dietary components have been shown to modify the inflammatory process at several steps of the inflammatory pathway. This review aims to evaluate the published literature on the effect of consumption of pro- or anti-inflammatory dietary constituents on the severity of both AD pathology and related chronic diseases, concentrating on the dietary constituents of flavonoids, spices, and fats. Diet-based anti-inflammatory components could lead to the development of potent novel anti-inflammatory compounds for a range of diseases. However, further work is required to fully characterize the therapeutic potential of such compounds, including gaining an understanding of dose-dependent relationships and limiting factors to effectiveness. Nutritional interventions utilizing anti-inflammatory foods may prove to be a valuable asset in not only delaying or preventing the development of age-related neurodegenerative diseases such as AD, but also treating pre-existing conditions including type-2 diabetes, cardiovascular disease, and obesity.

Medical conditions with neuropsychiatric manifestations.

PubMed

Isaac, Margaret L; Larson, Eric B

2014-09-01

Medical disease sometimes affects patients through neuropsychiatric manifestations. When neuropsychiatric symptoms are predominant, identifying medical disease early in the illness course is imperative because many of these conditions are reversible with appropriate treatment. A high index of suspicion is required on the part of clinicians, particularly when patients also present with physical signs or unexplained symptoms that might suggest a broader, systemic process. The processes that most commonly cause neuropsychiatric symptoms include infectious, autoimmune, endocrinologic, metabolic, and neoplastic diseases. This article focuses on the most common of these conditions, and conditions for which early diagnosis and treatment are particularly important. Copyright © 2014 Elsevier Inc. All rights reserved.

The Fruit Fly Drosophila melanogaster as a Model for Aging Research.

PubMed

Brandt, Annely; Vilcinskas, Andreas

2013-01-01

: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.

Magnesium in Disease Prevention and Overall Health12

PubMed Central

Volpe, Stella Lucia

2013-01-01

Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation and has been recognized as a cofactor for >300 metabolic reactions in the body. Some of the processes in which magnesium is a cofactor include, but are not limited to, protein synthesis, cellular energy production and storage, reproduction, DNA and RNA synthesis, and stabilizing mitochondrial membranes. Magnesium also plays a critical role in nerve transmission, cardiac excitability, neuromuscular conduction, muscular contraction, vasomotor tone, blood pressure, and glucose and insulin metabolism. Because of magnesium’s many functions within the body, it plays a major role in disease prevention and overall health. Low levels of magnesium have been associated with a number of chronic diseases including migraine headaches, Alzheimer’s disease, cerebrovascular accident (stroke), hypertension, cardiovascular disease, and type 2 diabetes mellitus. Good food sources of magnesium include unrefined (whole) grains, spinach, nuts, legumes, and white potatoes (tubers). This review presents recent research in the areas of magnesium and chronic disease, with the goal of emphasizing magnesium’s role in disease prevention and overall health. PMID:23674807

Application of 5-ALA for differential diagnostics of stomach diseases

NASA Astrophysics Data System (ADS)

Okhotnikova, Natalja L.; Dadvany, Sergey A.; Kuszin, Michail I.; Kharnas, Sergey S.; Zavodnov, Victor Y.; Sklyanskaya, Olga A.; Loschenov, Victor B.; Volkova, Anna I.; Agafonov, Valery V.

2001-01-01

59 patients with stomach diseases including gastric cancer or polyp, gastritis, esofagus disease were investigated. Before gastroscopy all patients were given 5-ALA in doses 5mg, 10mg and 20mg per 1kg of body weight orally. Fluorescence diagnostics which estimates concentration of ALA-induced PPIX in regular and alternated tissues of gastric mucosa were carried out in 2-4 hours. Using of 5-ALA has shown high diagnostic effectiveness for differential diagnostics of stomach diseases. This technique has proved 10 diagnosis of cancer and revealed 15 malignant stomach diseases including 4 cancer in situ for patients with preliminary diagnosis of gastric ulcer. It also revealed 5 patients with enhanced fluorescence for which aimed biopsy has shown high degree of inflammation process. The latter were assigned as a risk group.

The epidemiology of bovine respiratory disease: What is the evidence for preventive measures?

PubMed Central

Taylor, Jared D.; Fulton, Robert W.; Lehenbauer, Terry W.; Step, Douglas L.; Confer, Anthony W.

2010-01-01

Bovine respiratory disease (BRD) is the most common and costly disease of beef cattle in North America. Despite extensive research, industry practices are often more informed by dogma than by fact. Frequently advocated interventions, including vaccination, various processing procedures, and nutritional manipulation, have limited impact on morbidity and mortality. Evidence for use of oral antimicrobials, either in feed or water, appears to be equivocal. In contrast, preconditioning and metaphylaxis have significant scientific evidence of efficacy, with weaning prior to sale potentially being the most important component of preconditioning. The inability to reach more definitive conclusions in preventing BRD may be attributable to difficulties in investigating the disease. Study challenges include potential for extensive confounding, tremendous variability, the multi-factorial nature of the disease, and inadequate methods for diagnosis. PMID:21358927

Comparative effectiveness of colony-stimulating factors in febrile neutropenia prophylaxis: how results are affected by research design.

PubMed

Henk, Henry J; Li, Xiaoyan; Becker, Laura K; Xu, Hairong; Gong, Qi; Deeter, Robert G; Barron, Richard L

2015-01-01

To examine the impact of research design on results in two published comparative effectiveness studies. Guidelines for comparative effectiveness research have recommended incorporating disease process in study design. Based on the recommendations, we develop a checklist of considerations and apply the checklist in review of two published studies on comparative effectiveness of colony-stimulating factors. Both studies used similar administrative claims data, but different methods, which resulted in directionally different estimates. Major design differences between the two studies include: whether the timing of intervention in disease process was identified and whether study cohort and outcome assessment period were defined based on this temporal relationship. Disease process and timing of intervention should be incorporated into the design of comparative effectiveness studies.

Integrative medicine for chronic pain: A cohort study using a process-outcome design in the context of a department for internal and integrative medicine.

PubMed

Saha, Felix J; Brüning, Alexander; Barcelona, Cyrus; Büssing, Arndt; Langhorst, Jost; Dobos, Gustav; Lauche, Romy; Cramer, Holger

2016-07-01

Integrative medicine inpatient treatment has been shown to improve physical and mental health in patients with internal medicine conditions. The aim of this study was to investigate the effectiveness of a 2-week integrative medicine inpatient treatment in patients with chronic pain syndromes and the association of treatment success with patient-related process variables. Inpatients with chronic pain syndromes participating in a 2-week integrative medicine inpatient program were included. Patients' pain intensity, pain disability, pain perception, quality of life, depression, and perceived stress were measured on admission, discharge, and 6 months after discharge. Likewise process variables including ability and will to change, emotional/rational disease acceptance, mindfulness, life and health satisfaction, and easiness of life were assessed. A total of 310 inpatients (91% female, mean age 50.7 ± 12.4 year, 26.5% low back pain, and 22.9% fibromyalgia) were included. Using mixed linear models, significant improvements in pain intensity, pain disability, pain perception, quality of life, depression, and perceived stress were found (all P < 0.05). Ability to change and implementation, disease acceptance, mindfulness, life and health satisfaction, and light heartedness/easiness likewise improved (all P < 0.05). Improved outcomes were associated with increases in process variables, mainly ability to change and implementation, disease acceptance, life and health satisfaction, and light heartedness/easiness (R = 0.03-0.40). Results of this study suggest that a 2-week integrative medicine inpatient treatment can benefit patients with chronic pain conditions. Functional improvements are associated with improved ability to change and implementation, disease acceptance, and satisfaction.

Brain age and other bodily 'ages': implications for neuropsychiatry.

PubMed

Cole, James H; Marioni, Riccardo E; Harris, Sarah E; Deary, Ian J

2018-06-11

As our brains age, we tend to experience cognitive decline and are at greater risk of neurodegenerative disease and dementia. Symptoms of chronic neuropsychiatric diseases are also exacerbated during ageing. However, the ageing process does not affect people uniformly; nor, in fact, does the ageing process appear to be uniform even within an individual. Here, we outline recent neuroimaging research into brain ageing and the use of other bodily ageing biomarkers, including telomere length, the epigenetic clock, and grip strength. Some of these techniques, using statistical approaches, have the ability to predict chronological age in healthy people. Moreover, they are now being applied to neurological and psychiatric disease groups to provide insights into how these diseases interact with the ageing process and to deliver individualised predictions about future brain and body health. We discuss the importance of integrating different types of biological measurements, from both the brain and the rest of the body, to build more comprehensive models of the biological ageing process. Finally, we propose seven steps for the field of brain-ageing research to take in coming years. This will help us reach the long-term goal of developing clinically applicable statistical models of biological processes to measure, track and predict brain and body health in ageing and disease.

Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

PubMed

Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

2012-04-01

Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena, right pallidum, right thalamus, cerebellum, middle frontal, middle occipital, right superior and left inferior temporal gyri, and left superior parietal lobule. The modulated happiness network included postcentral gyri, left caudate, right cingulate cortex, right superior and inferior parietal lobules, and right superior frontal, middle temporal, middle occipital and precentral gyri. These effects were not driven merely by striatal dysfunction. We did not find equivalent associations between brain structure and emotion recognition, and the pre-manifest Huntington's disease cohort did not have a behavioural deficit in out-of-scanner emotion recognition relative to controls. In addition, we found increased neural activity in the pre-manifest subjects in response to all three emotions in frontal regions, predominantly in the middle frontal gyri. Overall, these findings suggest that pathophysiological effects of Huntington's disease may precede the development of overt clinical symptoms and detectable cerebral atrophy.

Inhibition of amyloid oligomerization into different supramolecular architectures by small molecules: mechanistic insights and design rules.

PubMed

Brahmachari, Sayanti; Paul, Ashim; Segal, Daniel; Gazit, Ehud

2017-05-01

Protein misfolding and aggregation have been associated with several human disorders, including Alzheimer's, Parkinson's and Huntington's diseases, as well as senile systemic amyloidosis and Type II diabetes. However, there is no current disease-modifying therapy available for the treatment of these disorders. In spite of extensive academic, pharmaceutical, medicinal and clinical research, a complete mechanistic model for this family of diseases is still lacking. In this review, we primarily discuss the different types of small molecular entities which have been used for the inhibition of the aggregation process of different amyloidogenic proteins under diseased conditions. These include small peptides, polyphenols, inositols, quinones and their derivatives, and metal chelator molecules. In recent years, these groups of molecules have been extensively studied using in vitro, in vivo and computational models to understand their mechanism of action and common structural features underlying the process of inhibition. A salient feature found to be instrumental in the process of inhibition is the balance between the aromatic unit that functions as the amyloid recognition unit and the hydrophilic amyloid breaker unit. The establishment of structure-function relationship for amyloid-modifying therapies by the various functional entities should serve as an important step toward the development of efficient therapeutics.

From Pathways to Targets: Understanding the Mechanisms behind Polyglutamine Disease

PubMed Central

Weber, Jonasz Jeremiasz; Sowa, Anna Sergeevna

2014-01-01

The history of polyglutamine diseases dates back approximately 20 years to the discovery of a polyglutamine repeat in the androgen receptor of SBMA followed by the identification of similar expansion mutations in Huntington's disease, SCA1, DRPLA, and the other spinocerebellar ataxias. This common molecular feature of polyglutamine diseases suggests shared mechanisms in disease pathology and neurodegeneration of disease specific brain regions. In this review, we discuss the main pathogenic pathways including proteolytic processing, nuclear shuttling and aggregation, mitochondrial dysfunction, and clearance of misfolded polyglutamine proteins and point out possible targets for treatment. PMID:25309920

Child and teacher acceptability of school-based echocardiographic screening for rheumatic heart disease in Uganda.

PubMed

Ploutz, Michelle; Aliku, Twalib; Bradley-Hewitt, Tyler; Dantin, Andrea; Lemley, Bethan; Gillespie, Catherine W; Lwabi, Peter; Sable, Craig; Beaton, Andrea

2017-01-01

Introduction Rheumatic heart disease causes substantial morbidity in children in low-income countries. School-based echocardiographic screening has been suggested as a means to identify children with latent disease; however, little is known about the experience of children and teachers participating in screenings. The aim of our study was to assess students' and teachers' experience of school-based echocardiographic screening and identify areas for improvement. Materials and methods A school-based echocardiographic screening programme was conducted in five schools in Northern Uganda in 2013. After 8 months, an age- and gender-stratified population that included 5% of the participating students and teachers completed a questionnaire via an in-person interview. Responses were reviewed by question and coded to identify key themes. A total of 255 students (mean 10.7 years; 48% male) and 35 teachers participated in our study. In total, 95% of the students and 100% of the teachers were happy to have participated in the screening; however, students reported feeling scared (35%) and nervous (48%) during the screening process. Programmatic strengths included the following: knowing one's health status, opportunity to receive treatment, and staff interactions. Although 43% of the patients did not suggest a change with open-ended questioning, concerns regarding privacy, fear of the screening process, and a desire to include others in the community were noted. Discussion School-based echocardiographic rheumatic heart disease screening was well received by students and teachers. Future programmes would likely benefit from improved pre-screening education regarding the screening process and diagnosis of rheumatic heart disease. Furthermore, education of teachers and students could improve screening perception and establish realistic expectations regarding the scope of screening.

Combining Image and Non-Image Data for Automatic Detection of Retina Disease in a Telemedicine Network

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

Aykac, Deniz; Chaum, Edward; Fox, Karen

A telemedicine network with retina cameras and automated quality control, physiological feature location, and lesion/anomaly detection is a low-cost way of achieving broad-based screening for diabetic retinopathy (DR) and other eye diseases. In the process of a routine eye-screening examination, other non-image data is often available which may be useful in automated diagnosis of disease. In this work, we report on the results of combining this non-image data with image data, using the protocol and processing steps of a prototype system for automated disease diagnosis of retina examinations from a telemedicine network. The system includes quality assessments, automated physiology detection,more » and automated lesion detection to create an archive of known cases. Non-image data such as diabetes onset date and hemoglobin A1c (HgA1c) for each patient examination are included as well, and the system is used to create a content-based image retrieval engine capable of automated diagnosis of disease into 'normal' and 'abnormal' categories. The system achieves a sensitivity and specificity of 91.2% and 71.6% using hold-one-out validation testing.« less

Basics of Radiation Biology When Treating Hyperproliferative Benign Diseases.

PubMed

Rödel, Franz; Fournier, Claudia; Wiedemann, Julia; Merz, Felicitas; Gaipl, Udo S; Frey, Benjamin; Keilholz, Ludwig; Seegenschmiedt, M Heinrich; Rödel, Claus; Hehlgans, Stephanie

2017-01-01

For decades, low- and moderate-dose radiation therapy (RT) has been shown to exert a beneficial therapeutic effect in a multitude of non-malignant conditions including painful degenerative muscoloskeletal and hyperproliferative disorders. Dupuytren and Ledderhose diseases are benign fibroproliferative diseases of the hand/foot with fibrotic nodules and fascial cords, which determine debilitating contractures and deformities of fingers/toes, while keloids are exuberant scar formations following burn damage, surgery, and trauma. Although RT has become an established and effective option in the management of these diseases, experimental studies to illustrate cellular composites and factors involved remain to be elucidated. More recent findings, however, indicate the involvement of radiation-sensitive targets like mitotic fibroblasts/myofibroblasts as well as inflammatory cells. Radiation-related molecular mechanisms affecting these target cells include the production of free radicals to hamper proliferative activity and interference with growth factors and cytokines. Moreover, an impairment of activated immune cells involved in both myofibroblast proliferative and inflammatory processes may further contribute to the clinical effects. We here aim at briefly describing mechanisms contributing to a modulation of proliferative and inflammatory processes and to summarize current concepts of treating hyperproliferative diseases by low and moderate doses of ionizing radiation.

Emerging infectious diseases in southeast Asia: regional challenges to control.

PubMed

Coker, Richard J; Hunter, Benjamin M; Rudge, James W; Liverani, Marco; Hanvoravongchai, Piya

2011-02-12

Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly decimated the region's tourist industry. Influenza A H5N1 has had a profound effect on the poultry industry. The reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in food production, agriculture and land use, water and sanitation, and the effect of health systems through generation of drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a city state with a gross domestic product (GDP) of US$37,500 per head, and Laos, until recently an overwhelmingly rural economy, with a GDP of US$890 per head. The regional challenges in control of emerging infectious diseases are formidable and range from influencing the factors that drive disease emergence, to making surveillance systems fit for purpose, and ensuring that regional governance mechanisms work effectively to improve control interventions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

PubMed Central

Soliman, Ashraf T.; Yasin, Mohamed; Kassem, Ahmed

2012-01-01

The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders) are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed. PMID:23565493

Impact of intermittent fasting on health and disease processes.

PubMed

Mattson, Mark P; Longo, Valter D; Harvie, Michelle

2017-10-01

Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state. Intermittent fasting (IF) encompasses eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis. We use the term periodic fasting (PF) to refer to IF with periods of fasting or fasting mimicking diets lasting from 2 to as many as 21 or more days. In laboratory rats and mice IF and PF have profound beneficial effects on many different indices of health and, importantly, can counteract disease processes and improve functional outcome in experimental models of a wide range of age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer's disease Parkinson's disease and stroke. Studies of IF (e.g., 60% energy restriction on 2days per week or every other day), PF (e.g., a 5day diet providing 750-1100kcal) and time-restricted feeding (TRF; limiting the daily period of food intake to 8h or less) in normal and overweight human subjects have demonstrated efficacy for weight loss and improvements in multiple health indicators including insulin resistance and reductions in risk factors for cardiovascular disease. The cellular and molecular mechanisms by which IF improves health and counteracts disease processes involve activation of adaptive cellular stress response signaling pathways that enhance mitochondrial health, DNA repair and autophagy. PF also promotes stem cell-based regeneration as well as long-lasting metabolic effects. Randomized controlled clinical trials of IF versus PF and isoenergetic continuous energy restriction in human subjects will be required to establish the efficacy of IF in improving general health, and preventing and managing major diseases of aging. Published by Elsevier B.V.

A randomized trial of an acid-peptic disease management program in a managed care environment.

PubMed

Ofman, Joshua J; Segal, Richard; Russell, Wayne L; Cook, Deborah J; Sandhu, Meenu; Maue, Susan K; Lowenstein, Edward H; Pourfarzib, Ray; Blanchette, Erv; Ellrodt, Gray; Weingarten, Scott R

2003-06-01

To study the effectiveness of a disease management program for patients with acid-related disorders. A cluster-randomized clinical trial of 406 patients comparing a disease management program with "usual practice." Enrolled patients included those presenting with new dyspepsia and chronic users of antisecretory drugs in 8 geographically separate physician offices associated with the Orlando Health Care Group. There were 35 providers in the intervention group and 48 in the control group. The disease management program included evidence-based practice guidelines implemented by using physician champions, academic detailing, and multidisciplinary teams. Processes of care, patient symptoms, quality of life, costs, and work days lost were measured 6 months after patient enrollment. Compared with usual practice, disease management was associated with improvements in Helicobacter pylori testing (61% vs 9%; P = .001), use of recommended H pylori treatment regimens (96% vs 10%; P = .001), and discontinuation rates of proton pump therapy after treatment (70% vs 36%; P = .04). There were few differences in patient quality of life or symptoms between the 2 study groups. Disease management resulted in fewer days of antisecretory therapy (71.7 vs 88.1 days; P = .02) but no difference in total costs. This disease management program for patients with acid-related disorders led to improved processes of care. The effectiveness of such a program in other settings requires further study.

Risks of beryllium disease related to work processes at a metal, alloy, and oxide production plant.

PubMed

Kreiss, K; Mroz, M M; Zhen, B; Wiedemann, H; Barna, B

1997-08-01

To describe relative hazards in sectors of the beryllium industry, risk factors of beryllium disease and sensitisation related to work process were sought in a beryllium manufacturing plant producing pure metal, oxide, alloys, and ceramics. All 646 active employees were interviewed; beryllium sensitisation was ascertained with the beryllium lymphocyte proliferation blood test on 627 employees; clinical evaluation and bronchoscopy were offered to people with abnormal test results; and industrial hygiene measurements related to work processes taken in 1984-93 were reviewed. 59 employees (9.4%) had abnormal blood tests, 47 of whom underwent bronchoscopy. 24 new cases of beryllium disease were identified, resulting in a beryllium disease prevalence of 4.6%, including five known cases (29/632). Employees who had worked in ceramics had the highest prevalence of beryllium disease (9.0%). Employees in the pebble plant (producing beryllium metal) who had been employed after 1983 also had increased risk, with a prevalence of beryllium disease of 6.4%, compared with 1.3% of other workers hired in the same period, and a prevalence of abnormal blood tests of 19.2%. Logistic regression modelling confirmed these two risk factors for beryllium disease related to work processes and the dependence on time of the risk at the pebble plant. The pebble plant was not associated with the highest gravimetric industrial hygiene measurements available since 1984. Further characterisation of exposures in beryllium metal production may be important to understanding how beryllium exposures confer high contemporary risk of beryllium disease.

Tone Discrimination as a Window into Acoustic Perceptual Deficits in Parkinson's Disease

ERIC Educational Resources Information Center

Troche, Joshua; Troche, Michelle S.; Berkowitz, Rebecca; Grossman, Murray; Reilly, Jamie

2012-01-01

Purpose: Deficits in auditory perception compromise a range of linguistic processes in persons with Parkinson's disease (PD), including speech perception and sensitivity to affective and linguistic prosody. An unanswered question is whether this deficit exists not only at the level of speech perception, but also at a more pervasive level of…

Rumination and behavioural factors in Parkinson's disease depression.

PubMed

Julien, Camille L; Rimes, Katharine A; Brown, Richard G

2016-03-01

Parkinson's disease is associated with high rates of depression. There is growing interest in non-pharmacological management including psychological approaches such as Cognitive Behaviour Therapy. To date, little research has investigated whether processes that underpin cognitive models of depression, on which such treatment is based, apply in patients with Parkinson's disease. The study aimed to investigate the contribution of core psychological factors to the presence and degree of depressive symptoms. 104 participants completed questionnaires measuring mood, motor disability and core psychological variables, including maladaptive assumptions, rumination, cognitive-behavioural avoidance, illness representations and cognitive-behavioural responses to symptoms. Regression analyses revealed that a small number of psychological factors accounted for the majority of depression variance, over and above that explained by overall disability. Participants reporting high levels of rumination, avoidance and symptom focusing experienced more severe depressive symptoms. In contrast, pervasive negative dysfunctional beliefs did not independently contribute to depression variance. Specific cognitive (rumination and symptom focusing) and behavioural (avoidance) processes may be key psychological markers of depression in Parkinson's disease and therefore offer important targets for tailored psychological interventions. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Endocytic Receptor Megalin and its Associated Proteins in Proximal Tubule Epithelial Cells

PubMed Central

De, Shankhajit; Kuwahara, Shoji; Saito, Akihiko

2014-01-01

Receptor-mediated endocytosis in renal proximal tubule epithelial cells (PTECs) is important for the reabsorption and metabolization of proteins and other substances, including carrier-bound vitamins and trace elements, in glomerular filtrates. Impairment of this endocytic process results in the loss of such substances and development of proteinuria, which is an important clinical indicator of kidney diseases and is also a risk marker for cardiovascular disease. Megalin, a member of the low-density lipoprotein receptor gene family, is a multiligand receptor expressed in the apical membrane of PTECs and plays a central role in the endocytic process. Megalin interacts with various intracellular adaptor proteins for intracellular trafficking and cooperatively functions with other membrane molecules, including the cubilin-amnionless complex. Evidence suggests that megalin and the cubilin-amnionless complex are involved in the uptake of toxic substances into PTECs, which leads to the development of kidney disease. Studies of megalin and its associated molecules will be useful for future development of novel strategies for the diagnosis and treatment of kidney diseases. PMID:25019425

Irritable bowel syndrome in quiescent inflammatory bowel disease: a review.

PubMed

Burgell, R E; Asthana, A K; Gibson, P R

2015-12-01

Ongoing troublesome bowel symptoms despite quiescent inflammatory disease are a frequent management challenge when caring for patients with inflammatory bowel disease (IBD). Even when active disease has been excluded the prevalence of residual gastrointestinal symptoms is surprisingly high and the cause often obscure. The presence of a concurrent functional disorder such as irritable bowel syndrome (IBS) is associated with worse quality of life, worse physical functioning, higher prevalence of anxiety and greater health care utilization. Potential etiological mechanisms leading to the development of IBS like symptoms include the development of visceral hypersensitivity following the original inflammatory insult, alteration in cortical processing, dysbiosis and residual subacute inflammation. Therapeutic options for managing IBS in patients with IBD include dietary modification, interventions targeted at correction of visceral sensory dysfunction or cortical processing and modulation of the gut microbiota. As there are few studies specifically examining the treatment of IBS in patients with IBD, the majority of therapeutic interventions are extrapolated from the IBS literature. Given the frequency of residual functional symptoms in IBS, significantly more research is warranted in this field.

40 CFR 63.1251 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to... this section. Consumption means the quantity of all HAP raw materials entering a process in excess of... as added as a raw material, consumption includes the quantity generated in the process. Container, as...

40 CFR 63.1251 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to... this section. Consumption means the quantity of all HAP raw materials entering a process in excess of... as added as a raw material, consumption includes the quantity generated in the process. Container, as...

Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders.

PubMed

Islam, Md Torequl

2017-01-01

Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body's antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA. Oxidative stress has been considered to be linked to the etiology of many diseases, including neurodegenerative diseases (NDDs) such as Alzheimer diseases, Amyotrophic lateral sclerosis, Friedreich's ataxia, Huntington's disease, Multiple sclerosis, and Parkinson's diseases. In addition, oxidative stress causing protein misfold may turn to other NDDs include Creutzfeldt-Jakob disease, Bovine Spongiform Encephalopathy, Kuru, Gerstmann-Straussler-Scheinker syndrome, and Fatal Familial Insomnia. An overview of the oxidative stress and mitochondrial dysfunction-linked NDDs has been summarized in this review.

Genetically manipulated mouse models of lung disease: potential and pitfalls

PubMed Central

Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

2012-01-01

Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

Inflammation in sickle cell disease.

PubMed

Conran, Nicola; Belcher, John D

2018-01-01

The primary β-globin gene mutation that causes sickle cell disease (SCD) has significant pathophysiological consequences that result in hemolytic events and the induction of the inflammatory processes that ultimately lead to vaso-occlusion. In addition to their role in the initiation of the acute painful vaso-occlusive episodes that are characteristic of SCD, inflammatory processes are also key components of many of the complications of the disease including autosplenectomy, acute chest syndrome, pulmonary hypertension, leg ulcers, nephropathy and stroke. We, herein, discuss the events that trigger inflammation in the disease, as well as the mechanisms, inflammatory molecules and cells that propagate these inflammatory processes. Given the central role that inflammation plays in SCD pathophysiology, many of the therapeutic approaches currently under pre-clinical and clinical development for the treatment of SCD endeavor to counter aspects or specific molecules of these inflammatory processes and it is possible that, in the future, we will see anti-inflammatory drugs being used either together with, or in place of, hydroxyurea in those SCD patients for whom hematopoietic stem cell transplants and evolving gene therapies are not a viable option.

The role of insufficient copper in lipid synthesis and fatty-liver disease.

PubMed

Morrell, Austin; Tallino, Savannah; Yu, Lei; Burkhead, Jason L

2017-04-01

The essential transition metal copper is important in lipid metabolism, redox balance, iron mobilization, and many other critical processes in eukaryotic organisms. Genetic diseases where copper homeostasis is disrupted, including Menkes disease and Wilson disease, indicate the importance of copper balance to human health. The severe consequences of insufficient copper supply are illustrated by Menkes disease, caused by mutation in the X-linked ATP7A gene encoding a protein that transports copper from intestinal epithelia into the bloodstream and across the blood-brain barrier. Inadequate copper supply to the body due to poor diet quality or malabsorption can disrupt several molecular level pathways and processes. Though much of the copper distribution machinery has been described and consequences of disrupted copper handling have been characterized in human disease as well as animal models, physiological consequences of sub-optimal copper due to poor nutrition or malabsorption have not been extensively studied. Recent work indicates that insufficient copper may be important in a number of common diseases including obesity, ischemic heart disease, and metabolic syndrome. Specifically, marginal copper deficiency (CuD) has been reported as a potential etiologic factor in diseases characterized by disrupted lipid metabolism such as non-alcoholic fatty-liver disease (NAFLD). In this review, we discuss the available data suggesting that a significant portion of the North American population may consume insufficient copper, the potential mechanisms by which CuD may promote lipid biosynthesis, and the interaction between CuD and dietary fructose in the etiology of NAFLD. © 2016 IUBMB Life, 69(4):263-270, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Red meat, diseases, and healthy alternatives: A critical review.

PubMed

Ekmekcioglu, Cem; Wallner, Peter; Kundi, Michael; Weisz, Ulli; Haas, Willi; Hutter, Hans-Peter

2018-01-22

Meat is an important food for human nutrition, by especially providing high-quality protein and also some essential micronutrients, in front iron, zinc, and vitamin B 12 . However, a high intake of red and processed meat is associated with an increased risk for diseases, especially type 2 diabetes and colorectal cancer, as several epidemiological studies and meta-analyses have shown. This review summarizes meta-analyses of publications studying the association between red and processed meat intake and type 2 diabetes, cardiovascular diseases, colorectal and other cancers, and all-cause mortality. Various potential mechanisms involved in the increased disease risk are discussed. Furthermore, the beneficial effects of healthy alternatives for meat, like fish, nuts, vegetables and fruits, pulses and legumes, whole grains, and dairy products are reviewed by including selected papers and recent meta-analyses.

The role of trophic factors and inflammatory processes in physical activity-induced neuroprotection in Parkinson's disease.

PubMed

Pałasz, Ewelina; Bąk, Agnieszka; Gąsiorowska, Anna; Niewiadomska, Grażyna

2017-01-04

Glial cells and neurotrophins play an important role in maintaining homeostasis of the CNS. Disturbances of their function can lead to a number of nervous system diseases, including Parkinson's disease (PD). Current clinical studies provide evidence that moderate physical activity adapted to the health status of PD patients can support pharmacological treatment, slow down the onset of motor impairments, and extend the patients period of independence. Physical activity, by stimulating the production and release of endogenous trophic factors, prevents the neurodegeneration of dopaminergic neurons via inhibition of inflammatory processes and the reduction of oxidative stress. The aim of this study is to present the current state of knowledge for the anti-inflammatory and neuroprotective properties of physical activity as a supportive therapy in Parkinson's disease.

Lung and Heart Sounds Analysis: State-of-the-Art and Future Trends.

PubMed

Padilla-Ortiz, Ana L; Ibarra, David

2018-01-01

Lung sounds, which include all sounds that are produced during the mechanism of respiration, may be classified into normal breath sounds and adventitious sounds. Normal breath sounds occur when no respiratory problems exist, whereas adventitious lung sounds (wheeze, rhonchi, crackle, etc.) are usually associated with certain pulmonary pathologies. Heart and lung sounds that are heard using a stethoscope are the result of mechanical interactions that indicate operation of cardiac and respiratory systems, respectively. In this article, we review the research conducted during the last six years on lung and heart sounds, instrumentation and data sources (sensors and databases), technological advances, and perspectives in processing and data analysis. Our review suggests that chronic obstructive pulmonary disease (COPD) and asthma are the most common respiratory diseases reported on in the literature; related diseases that are less analyzed include chronic bronchitis, idiopathic pulmonary fibrosis, congestive heart failure, and parenchymal pathology. Some new findings regarding the methodologies associated with advances in the electronic stethoscope have been presented for the auscultatory heart sound signaling process, including analysis and clarification of resulting sounds to create a diagnosis based on a quantifiable medical assessment. The availability of automatic interpretation of high precision of heart and lung sounds opens interesting possibilities for cardiovascular diagnosis as well as potential for intelligent diagnosis of heart and lung diseases.

Sudden death in Lesch-Nyhan disease.

PubMed

Neychev, Vladimir Kostadinov; Jinnah, H A

2006-11-01

To increase awareness of sudden and unexpected death in Lesch-Nyhan disease (LND) and to explore its potential causes, we report the anteceding clinical features and laboratory evaluations of five males with LND who ultimately experienced sudden and unexpected death, along with three additional males who suffered serious respiratory events during life. The ages of patients ranged from 2 to 45 years. The cause of sudden death in LND appears to have a respiratory rather than a cardiogenic basis. All cases cannot be linked readily with a single respiratory process. Instead, different respiratory processes appear to operate in different cases. These may include aspiration, laryngospasm, central apnea, cyanotic breath-holding spells, and high cervical spine damage. Better recognition of these processes will help to guide appropriate workup and management that could include chest imaging, endoscopy of the airways, polysomnography, electroencephalogram, and brain and/or spine imaging.

Thalassaemia.

PubMed

Taher, Ali T; Weatherall, David J; Cappellini, Maria Domenica

2018-01-13

Inherited haemoglobin disorders, including thalassaemia and sickle-cell disease, are the most common monogenic diseases worldwide. Several clinical forms of α-thalassaemia and β-thalassaemia, including the co-inheritance of β-thalassaemia with haemoglobin E resulting in haemoglobin E/β-thalassaemia, have been described. The disease hallmarks include imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic haemolytic anaemia, compensatory haemopoietic expansion, hypercoagulability, and increased intestinal iron absorption. The complications of iron overload, arising from transfusions that represent the basis of disease management in most patients with severe thalassaemia, might further complicate the clinical phenotype. These pathophysiological mechanisms lead to an array of clinical manifestations involving numerous organ systems. Conventional management primarily relies on transfusion and iron-chelation therapy, as well as splenectomy in specific cases. An increased understanding of the molecular and pathogenic factors that govern the disease process have suggested routes for the development of new therapeutic approaches that address the underlying chain imbalance, ineffective erythropoiesis, and iron dysregulation, with several agents being evaluated in preclinical models and clinical trials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Spatial autocorrelation among automated geocoding errors and its effects on testing for disease clustering

PubMed Central

Li, Jie; Fang, Xiangming

2010-01-01

Automated geocoding of patient addresses is an important data assimilation component of many spatial epidemiologic studies. Inevitably, the geocoding process results in positional errors. Positional errors incurred by automated geocoding tend to reduce the power of tests for disease clustering and otherwise affect spatial analytic methods. However, there are reasons to believe that the errors may often be positively spatially correlated and that this may mitigate their deleterious effects on spatial analyses. In this article, we demonstrate explicitly that the positional errors associated with automated geocoding of a dataset of more than 6000 addresses in Carroll County, Iowa are spatially autocorrelated. Furthermore, through two simulation studies of disease processes, including one in which the disease process is overlain upon the Carroll County addresses, we show that spatial autocorrelation among geocoding errors maintains the power of two tests for disease clustering at a level higher than that which would occur if the errors were independent. Implications of these results for cluster detection, privacy protection, and measurement-error modeling of geographic health data are discussed. PMID:20087879

Demyelination of vestibular nerve axons in unilateral Ménière's disease.

PubMed

Spencer, Robert F; Sismanis, Aristides; Kilpatrick, Jefferson K; Shaia, Wayne T

2002-11-01

We conducted a study to determine whether vestibular nerves in patients with unilateral Ménière's disease whose symptoms are refractory to medical management exhibit neuropathologic changes. We also endeavored to determine whether retrocochlear abnormalities are primary or secondary factors in the disease process. To these ends, we obtained vestibular nerve segments from five patients during retrosigmoid (posterior fossa) neurectomy, immediately fixed them, and processed them for light and electron microscopy. We found that all five segments exhibited moderate to severe demyelination with axonal sparing. Moreover, we noted that reactive astrocytes produced an extensive proliferation of fibrous processes and that the microglia assumed a phagocytic role. We conclude that the possible etiologies of demyelination include viral and/or immune-mediated factors similar to those seen in other demyelinating diseases, such as multiple sclerosis and Guillain-Barré syndrome. Our findings suggest that some forms of Ménière's disease that are refractory to traditional medical management might be the result of retrocochlear pathology that affects the neuroglial portion of the vestibular nerve.

Enhancing surveillance for hepatitis C through public health informatics.

PubMed

Heisey-Grove, Dawn M; Church, Daniel R; Haney, Gillian A; Demaria, Alfred

2011-01-01

Disease surveillance for hepatitis C in the United States is limited by the occult nature of many of these infections, the large volume of cases, and limited public health resources. Through a series of discrete processes, the Massachusetts Department of Public Health modified its surveillance system in an attempt to improve timeliness and completeness of reporting and case follow-up of hepatitis C. These processes included clinician-based reporting, electronic laboratory reporting, deployment of a Web-based disease surveillance system, automated triage of pertinent data, and automated character recognition software for case-report processing. These changes have resulted in an increase in the timeliness of reporting.

Metabolomics - the complementary field in systems biology: a review on obesity and type 2 diabetes.

PubMed

Abu Bakar, Mohamad Hafizi; Sarmidi, Mohamad Roji; Cheng, Kian-Kai; Ali Khan, Abid; Suan, Chua Lee; Zaman Huri, Hasniza; Yaakob, Harisun

2015-07-01

Metabolomic studies on obesity and type 2 diabetes mellitus have led to a number of mechanistic insights into biomarker discovery and comprehension of disease progression at metabolic levels. This article reviews a series of metabolomic studies carried out in previous and recent years on obesity and type 2 diabetes, which have shown potential metabolic biomarkers for further evaluation of the diseases. Literature including journals and books from Web of Science, Pubmed and related databases reporting on the metabolomics in these particular disorders are reviewed. We herein discuss the potential of reported metabolic biomarkers for a novel understanding of disease processes. These biomarkers include fatty acids, TCA cycle intermediates, carbohydrates, amino acids, choline and bile acids. The biological activities and aetiological pathways of metabolites of interest in driving these intricate processes are explained. The data from various publications supported metabolomics as an effective strategy in the identification of novel biomarkers for obesity and type 2 diabetes. Accelerating interest in the perspective of metabolomics to complement other fields in systems biology towards the in-depth understanding of the molecular mechanisms underlying the diseases is also well appreciated. In conclusion, metabolomics can be used as one of the alternative approaches in biomarker discovery and the novel understanding of pathophysiological mechanisms in obesity and type 2 diabetes. It can be foreseen that there will be an increasing research interest to combine metabolomics with other omics platforms towards the establishment of detailed mechanistic evidence associated with the disease processes.

Potato Production, Usage, and Nutrition--A Review.

PubMed

Zaheer, Khalid; Akhtar, M Humayoun

2016-01-01

Potato is an economically important staple crop prevailing all across the world with successful large-scale production, consumption, and affordability with easy availability in the open market. Potatoes provide basic nutrients such as-carbohydrates, dietary fiber (skin), several vitamins, and minerals (e.g., potassium, magnesium, iron). On occasion exposures to raw and cooked potatoes impart allergic reactions. Dietary intake of potatoes, especially colored potatoes, play an important role in the production of antioxidant defense system by providing essential nutrient antioxidants, such as vitamins, β-carotene, polyphenols, and minerals. This may help lower the incidence of wide range of chronic and acute disease processes (like hypertension, heart diseases, cancer, neurodegenerative, and other diseases). However, retention of nutrients in potatoes is affected by various cooking and processing methods. Cooking at elevated temperature also produces acrylamide-a suspected carcinogen. Independent and/or collaborative studies have been conducted and reported on the various pathways leading to the formation of acrylamide in heat processed foods. This article reviews the latest research on potato production, consumption, nature of phytochemicals and their health benefits, and allergic reactions to children. Also included is the discovery of acrylamide in processed starch-rich foods including potatoes, mechanism of formation, detection methodologies, and mitigation steps to reduce acrylamide content in food.

Noninvasive Molecular Imaging of Disease Activity in Atherosclerosis

PubMed Central

Aikawa, Elena; Newby, David E.; Tarkin, Jason M.; Rudd, James H.F.; Narula, Jagat; Fayad, Zahi A.

2016-01-01

Major focus has been placed on the identification of vulnerable plaques as a means of improving the prediction of myocardial infarction. However, this strategy has recently been questioned on the basis that the majority of these individual coronary lesions do not in fact go on to cause clinical events. Attention is, therefore, shifting to alternative imaging modalities that might provide a more complete pan-coronary assessment of the atherosclerotic disease process. These include markers of disease activity with the potential to discriminate between patients with stable burnt-out disease that is no longer metabolically active and those with active atheroma, faster disease progression, and increased risk of infarction. This review will examine how novel molecular imaging approaches can provide such assessments, focusing on inflammation and microcalcification activity, the importance of these processes to coronary atherosclerosis, and the advantages and challenges posed by these techniques. PMID:27390335

Consensus Paper: Pathological Mechanisms Underlying Neurodegeneration in Spinocerebellar Ataxias

PubMed Central

Matilla-Dueñas, A.; Ashizawa, T.; Brice, A.; Magri, S.; McFarland, K. N.; Pandolfo, M.; Pulst, S. M.; Riess, O.; Rubinsztein, D. C.; Schmidt, J.; Schmidt, T.; Scoles, D. R.; Stevanin, G.; Taroni, F.; Underwood, B. R.; Sánchez, I.

2014-01-01

Intensive scientific research devoted in the recent years to understand the molecular mechanisms or neurodegeneration in spinocerebellar ataxias (SCAs) are identifying new pathways and targets providing new insights and a better understanding of the molecular pathogenesis in these diseases. In this consensus manuscript, the authors discuss their current views on the identified molecular processes causing or modulating the neurodegenerative phenotype in spinocerebellar ataxias with the common opinion of translating the new knowledge acquired into candidate targets for therapy. The following topics are discussed: transcription dysregulation, protein aggregation, autophagy, ion channels, the role of mitochondria, RNA toxicity, modulators of neurodegeneration and current therapeutic approaches. Overall point of consensus includes the common vision of neurodegeneration in SCAs as a multifactorial, progressive and reversible process, at least in early stages. Specific points of consensus include the role of the dysregulation of protein folding, transcription, bioenergetics, calcium handling and eventual cell death with apoptotic features of neurons during SCA disease progression. Unresolved questions include how the dysregulation of these pathways triggers the onset of symptoms and mediates disease progression since this understanding may allow effective treatments of SCAs within the window of reversibility to prevent early neuronal damage. Common opinions also include the need for clinical detection of early neuronal dysfunction, for more basic research to decipher the early neurodegenerative process in SCAs in order to give rise to new concepts for treatment strategies and for the translation of the results to preclinical studies and, thereafter, in clinical practice. PMID:24307138

HACCP-Based Programs for Preventing Disease and Injury from Premise Plumbing: A Building Consensus

PubMed Central

McCoy, William F.; Rosenblatt, Aaron A.

2015-01-01

Thousands of preventable injuries and deaths are annually caused by microbial, chemical and physical hazards from building water systems. Water is processed in buildings before use; this can degrade the quality of the water. Processing steps undertaken on-site in buildings often include conditioning, filtering, storing, heating, cooling, pressure regulation and distribution through fixtures that restrict flow and temperature. Therefore, prevention of disease and injury requires process management. A process management framework for buildings is the hazard analysis and critical control point (HACCP) adaptation of failure mode effects analysis (FMEA). It has been proven effective for building water system management. Validation is proof that hazards have been controlled under operating conditions and may include many kinds of evidence including cultures of building water samples to detect and enumerate potentially pathogenic microorganisms. However, results from culture tests are often inappropriately used because the accuracy and precision are not sufficient to support specifications for control limit or action triggers. A reliable negative screen is based on genus-level Polymerase Chain Reaction (PCR) for Legionella in building water systems; however, building water samples with positive results from this test require further analysis by culture methods. PMID:26184325

HACCP-Based Programs for Preventing Disease and Injury from Premise Plumbing: A Building Consensus.

PubMed

McCoy, William F; Rosenblatt, Aaron A

2015-07-09

Thousands of preventable injuries and deaths are annually caused by microbial, chemical and physical hazards from building water systems. Water is processed in buildings before use; this can degrade the quality of the water. Processing steps undertaken on-site in buildings often include conditioning, filtering, storing, heating, cooling, pressure regulation and distribution through fixtures that restrict flow and temperature. Therefore, prevention of disease and injury requires process management. A process management framework for buildings is the hazard analysis and critical control point (HACCP) adaptation of failure mode effects analysis (FMEA). It has been proven effective for building water system management. Validation is proof that hazards have been controlled under operating conditions and may include many kinds of evidence including cultures of building water samples to detect and enumerate potentially pathogenic microorganisms. However, results from culture tests are often inappropriately used because the accuracy and precision are not sufficient to support specifications for control limit or action triggers. A reliable negative screen is based on genus-level Polymerase Chain Reaction (PCR) for Legionella in building water systems; however, building water samples with positive results from this test require further analysis by culture methods.

What's in a Name?

ERIC Educational Resources Information Center

Tasse, Marc J.

2013-01-01

The World Health Organization (WHO) is in the process of developing the 11th edition of the "International Classification of Diseases" ("ICD-11"). Part of this process includes replacing "mental retardation" with a more acceptable term to identify the condition. The current international consensus appears to be replacing "mental retardation" with…

Large scale isolation and purification of soluble RAGE from lung tissue.

PubMed

Englert, Judson M; Ramsgaard, Lasse; Valnickova, Zuzana; Enghild, Jan J; Oury, Tim D

2008-09-01

The receptor for advanced glycation end-products (RAGE) has been implicated in numerous disease processes including: atherosclerosis, diabetic nephropathy, impaired wound healing and neuropathy to name a few. Treatment of animals with a soluble isoform of the receptor (sRAGE) has been shown to prevent and even reverse many disease processes. Isolating large quantities of pure sRAGE for in vitro and in vivo studies has hindered its development as a therapeutic strategy in other RAGE mediated diseases that require long-term therapy. This article provides an improvement in both yield and detail of a previously published method to obtain 10mg of pure, endotoxin free sRAGE from 65 g of lung tissue.

Guideline group composition and group processes: article 3 in Integrating and coordinating efforts in COPD guideline development. An official ATS/ERS workshop report.

PubMed

Kunz, Regina; Fretheim, Atle; Cluzeau, Françoise; Wilt, Timothy J; Qaseem, Amir; Lelgemann, Monika; Kelson, Marcia; Guyatt, Gordon; Schünemann, Holger J

2012-12-01

Professional societies, like many other organizations around the world, have recognized the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the third of a series of 14 articles that were prepared to advise guideline developers in respiratory and other diseases on considerations for group compositions and group processes in guideline development, and how this can be effectively integrated in the context of respiratory disease guidelines on a national and international level. We updated a review of the literature addressing group composition and group process, focusing on the following questions: 1. How to compose a functioning and representative guideline group; Who should be included in a guideline panel?; How to select organizations, groups, and individuals; What expertise is needed?; Consultation with non-included groups. 2. How to assure a functioning group process; How to make the process constructive; Balancing participation and finding agreement; Administrative support; What constitutes sufficient resources? Our conclusions are based on available evidence from published literature, experience from guideline developers, and workshop discussions. Formal studies addressing optimal processes in developing guidelines are limited, and experience from guideline organizations supplement the formal studies. When resources are available, guideline development groups should aim for multidisciplinary groups, including patients. Prerequisites for a multidisciplinary group include: a strong chair experienced in group facilitation with broad acceptance in the group, training the group in guideline methodology, and professional technical support. Formal consensus developing methods have proved effective in reaching agreement on the final recommendations.

Convergent molecular defects underpin diverse neurodegenerative diseases.

PubMed

Tofaris, George K; Buckley, Noel J

2018-02-19

In our ageing population, neurodegenerative disorders carry an enormous personal, societal and economic burden. Although neurodegenerative diseases are often thought of as clinicopathological entities, increasing evidence suggests a considerable overlap in the molecular underpinnings of their pathogenesis. Such overlapping biological processes include the handling of misfolded proteins, defective organelle trafficking, RNA processing, synaptic health and neuroinflammation. Collectively but in different proportions, these biological processes in neurons or non-neuronal cells lead to regionally distinct patterns of neuronal vulnerability and progression of pathology that could explain the disease symptomology. With the advent of patient-derived cellular models and novel genetic manipulation tools, we are now able to interrogate this commonality despite the cellular complexity of the brain in order to develop novel therapeutic strategies to prevent or arrest neurodegeneration. Here, we describe broadly these concepts and their relevance across neurodegenerative diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways

PubMed Central

Sturgeon, John A.; Finan, Patrick H.; Zautra, Alex J.

2017-01-01

In addition to recurrent pain, fatigue, and increased rates of physical disability, individuals with rheumatoid arthritis (RA) show an increased prevalence of some mental health disorders, particularly those involving mood disturbances. This narrative Review provides an overview of mental health comorbidities in RA, and discusses how these comorbidities interact with disease processes, including dysregulation of inflammatory responses, prolonged difficulties with pain and fatigue, and the development of cognitive and behavioural responses that could exacerbate the physical and psychological difficulties associated with RA. This article describes how the social context of individuals with RA affects both their coping strategies and psychological responses to the disease, and can also impair responses to treatment through disruption of therapeutic alliance and treatment adherence. Evidence from the literature on chronic pain suggests that the resulting alterations in neural pathways of reward processing could yield new insights into the connections between disease processes in RA and psychological distress. Finally, the role of psychological interventions in the effective and comprehensive treatment of RA is discussed. PMID:27411910

Mitochondria in lung disease

PubMed Central

Cloonan, Suzanne M.; Choi, Augustine M.K.

2016-01-01

Mitochondria are a distinguishing feature of eukaryotic cells. Best known for their critical function in energy production via oxidative phosphorylation (OXPHOS), mitochondria are essential for nutrient and oxygen sensing and for the regulation of critical cellular processes, including cell death and inflammation. Such diverse functional roles for organelles that were once thought to be simple may be attributed to their distinct heteroplasmic genome, exclusive maternal lineage of inheritance, and ability to generate signals to communicate with other cellular organelles. Mitochondria are now thought of as one of the cell’s most sophisticated and dynamic responsive sensing systems. Specific signatures of mitochondrial dysfunction that are associated with disease pathogenesis and/or progression are becoming increasingly important. In particular, the centrality of mitochondria in the pathological processes and clinical phenotypes associated with a range of lung diseases is emerging. Understanding the molecular mechanisms regulating the mitochondrial processes of lung cells will help to better define phenotypes and clinical manifestations associated with respiratory disease and to identify potential diagnostic and therapeutic targets. PMID:26928034

Developing Disease-Modifying Treatments in Alzheimer's Disease - A Perspective from Roche and Genentech.

PubMed

Doody, R

2017-01-01

Alzheimer's disease (AD) is a chronic neurodegenerative disease for which no preventative or disease-modifying treatments currently exist. Pathological hallmarks include amyloid plaques and neurofibrillary tangles composed of hyper-phosphorylated tau protein. Evidence suggests that both pathologies are self-propagating once established. However, the lag time between neuropathological changes in the brain and the onset of even subtle clinical symptomatology means that patients are often diagnosed late when pathology, and neurodegeneration secondary to these changes, may have been established for several years. Complex pathological pathways associated with susceptibility to AD and changes that occur downstream of the neuropathologic process further contribute to the challenging endeavour of developing novel disease-modifying therapy. Recognising this complexity, effective management of AD must include reliable screening and early diagnosis in combination with effective therapeutic management of the pathological processes. Roche and Genentech are committed to addressing these unmet needs through developing a comprehensive portfolio of diagnostics and novel therapies. Beginning with the most scientifically supported targets, this approach includes two targeted amyloid-β monoclonal antibody therapies, crenezumab and gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as well as a robust biomarker platform to aid in the early identification of people at risk or in the early stages of AD. Identification and implementation of diagnostic tools will support the enrolment of patients into clinical trials; furthermore, these tools should also support evaluation of the clinical efficacy and safety profile of the novel therapeutic agents tested in these trials. This review discusses the therapeutic agents currently under clinical development.

Evaluation of a regional disease management programme for patients with asthma or chronic obstructive pulmonary disease.

PubMed

Steuten, Lotte; Vrijhoef, Bert; Van Merode, Frits; Wesseling, Geert-Jan; Spreeuwenberg, Cor

2006-12-01

To assess the impact of a population-based disease management programme for adult patients with asthma or chronic obstructive pulmonary disease (COPD) on process measures, intermediate outcomes, and endpoints of care. Quasi-experimental design with 12-month follow-up. Region of Maastricht (the Netherlands) including university hospital and 16 general practices. Nine hundred and seventy-five patients of whom 658 have asthma and 317 COPD. Disease management programme. Endpoints of care are respiratory health, health utility, patient satisfaction, and total health care costs related to asthma or COPD. Quality aspects of care, disease control, self-care behaviour, smoking status, disease-specific knowledge, and patients' satisfaction improved after implementation of the programme. Lung function was not affected by implementation of the programme. For COPD patients, a significant improvement in health utility was found. For patients with asthma, significant cost savings were measured. Organizing health care according to principles of disease management for adults with asthma or COPD is associated with significant improvements in several processes and outcomes of care, while costs of care do not exceed the existing budget.

Clinical performance improvement series. Classic CQI integrated with comprehensive disease management as a model for performance improvement.

PubMed

Joshi, M S; Bernard, D B

1999-08-01

In recent years, health and disease management has emerged as an effective means of delivering, integrating, and improving care through a population-based approach. Since 1997 the University of Pennsylvania Health System (UPHS) has utilized the key principles and components of continuous quality improvement (CQI) and disease management to form a model for health care improvement that focuses on designing best practices, using best practices to influence clinical decision making, changing processes and systems to deploy and deliver best practices, and measuring outcomes to improve the process. Experience with 28 programs and more than 14,000 patients indicates significant improvement in outcomes, including high physician satisfaction, increased patient satisfaction, reduced costs, and improved clinical process and outcome measures across multiple diseases. DIABETES DISEASE MANAGEMENT: In three months a UPHS multidisciplinary diabetes disease management team developed a best practice approach for the treatment of all patients with diabetes in the UPHS. After the program was pilot tested in three primary care physician sites, it was then introduced progressively to additional practice sites throughout the health system. The establishment of the role of the diabetes nurse care managers (certified diabetes educators) was central to successful program deployment. Office-based coordinators ensure incorporation of the best practice protocols into routine flow processes. A disease management intranet disseminates programs electronically. Outcomes of the UPHS health and disease management programs so far demonstrate success across multiple dimensions of performance-service, clinical quality, access, and value. The task of health care leadership today is to remove barriers and enable effective implementation of key strategies, such as health and disease management. Substantial effort and resources must be dedicated to gain physician buy-in and achieve compliance. The challenge is to provide leadership support, to reward and recognize best practice performers, and to emphasize the use of data for feedback and improvement. As these processes are implemented successfully, and evidence of improved outcomes is documented, it is likely that this approach will be more widely embraced and that organizationwide performance improvement will increase significantly. Health care has traditionally invested extraordinary resources in developing best practice approaches, including guidelines, education programs, or other tangible products and services. Comparatively little time, effort, and resources have been targeted to implementation and use, the stage at which most efforts fail. CQI's emphasis on data, rapid diffusion of innovative programs, and rapid cycle improvements enhance the implementation and effectiveness of disease management.

Integrative medicine for chronic pain

PubMed Central

Saha, Felix J.; Brüning, Alexander; Barcelona, Cyrus; Büssing, Arndt; Langhorst, Jost; Dobos, Gustav; Lauche, Romy; Cramer, Holger

2016-01-01

Abstract Introduction: Integrative medicine inpatient treatment has been shown to improve physical and mental health in patients with internal medicine conditions. The aim of this study was to investigate the effectiveness of a 2-week integrative medicine inpatient treatment in patients with chronic pain syndromes and the association of treatment success with patient-related process variables. Methods: Inpatients with chronic pain syndromes participating in a 2-week integrative medicine inpatient program were included. Patients’ pain intensity, pain disability, pain perception, quality of life, depression, and perceived stress were measured on admission, discharge, and 6 months after discharge. Likewise process variables including ability and will to change, emotional/rational disease acceptance, mindfulness, life and health satisfaction, and easiness of life were assessed. Results: A total of 310 inpatients (91% female, mean age 50.7 ± 12.4 year, 26.5% low back pain, and 22.9% fibromyalgia) were included. Using mixed linear models, significant improvements in pain intensity, pain disability, pain perception, quality of life, depression, and perceived stress were found (all P < 0.05). Ability to change and implementation, disease acceptance, mindfulness, life and health satisfaction, and light heartedness/easiness likewise improved (all P < 0.05). Improved outcomes were associated with increases in process variables, mainly ability to change and implementation, disease acceptance, life and health satisfaction, and light heartedness/easiness (R2 = 0.03–0.40). Conclusions: Results of this study suggest that a 2-week integrative medicine inpatient treatment can benefit patients with chronic pain conditions. Functional improvements are associated with improved ability to change and implementation, disease acceptance, and satisfaction. PMID:27399133

Therapeutic strategies for allergic diseases

NASA Astrophysics Data System (ADS)

Barnes, Peter J.

1999-11-01

Many drugs are now in development for the treatment of atopic diseases, including asthma, allergic rhinitis and atopic dermatitis. These treatments are based on improvements in existing therapies or on a better understanding of the cellular and molecular mechanisms involved in atopic diseases. Although most attention has been focused on asthma, treatments that inhibit the atopic disease process would have application to all atopic diseases, as they often coincide. Most of the many new therapies in development are aimed at inhibiting components of the allergic inflammatory response, but in the future there are real possibilities for the development of preventative and even curative treatments.

Occupational Disease Registries–Characteristics and Experiences

PubMed Central

Davoodi, Somayeh; Haghighi, Khosro Sadeghniat; Kalhori, Sharareh Rostam Niakan; Hosseini, Narges Shams; Mohammadzadeh, Zeinab; Safdari, Reza

2017-01-01

Introduction: Due to growth of occupational diseases and also increase of public awareness about their consequences, attention to various aspects of diseases and improve occupational health and safety has found great importance. Therefore, there is the need for appropriate information management tools such as registries in order to recognitions of diseases patterns and then making decision about prevention, early detection and treatment of them. These registries have different characteristics in various countries according to their occupational health priorities. Aim: Aim of this study is evaluate dimensions of occupational diseases registries including objectives, data sources, responsible institutions, minimum data set, classification systems and process of registration in different countries. Material and Methods: In this study, the papers were searched using the MEDLINE (PubMed) Google scholar, Scopus, ProQuest and Google. The search was done based on keyword in English for all motor engines including “occupational disease”, “work related disease”, “surveillance”, “reporting”, “registration system” and “registry” combined with name of the countries including all subheadings. After categorizing search findings in tables, results were compared with each other. Results: Important aspects of the registries studied in ten countries including Finland, France, United Kingdom, Australia, Czech Republic, Malaysia, United States, Singapore, Russia and Turkey. The results show that surveyed countries have statistical, treatment and prevention objectives. Data sources in almost the rest of registries were physicians and employers. The minimum data sets in most of them consist of information about patient, disease, occupation and employer. Some of countries have special occupational related classification systems for themselves and some of them apply international classification systems such as ICD-10. Finally, the process of registration system was different in countries. Conclusion: Because occupational diseases are often preventable, but not curable, it is necessary to all countries, to consider prevention and early detection of occupational diseases as the objectives of their registry systems. Also it is recommended that all countries reach an agreement about global characteristics of occupational disease registries. This enables country to compare their data at international levels. PMID:28883681

Prediction of human disease-associated phosphorylation sites with combined feature selection approach and support vector machine.

PubMed

Xu, Xiaoyi; Li, Ao; Wang, Minghui

2015-08-01

Phosphorylation is a crucial post-translational modification, which regulates almost all cellular processes in life. It has long been recognised that protein phosphorylation has close relationship with diseases, and therefore many researches are undertaken to predict phosphorylation sites for disease treatment and drug design. However, despite the success achieved by these approaches, no method focuses on disease-associated phosphorylation sites prediction. Herein, for the first time the authors propose a novel approach that is specially designed to identify associations between phosphorylation sites and human diseases. To take full advantage of local sequence information, a combined feature selection method-based support vector machine (CFS-SVM) that incorporates minimum-redundancy-maximum-relevance filtering process and forward feature selection process is developed. Performance evaluation shows that CFS-SVM is significantly better than the widely used classifiers including Bayesian decision theory, k nearest neighbour and random forest. With the extremely high specificity of 99%, CFS-SVM can still achieve a high sensitivity. Besides, tests on extra data confirm the effectiveness and general applicability of CFS-SVM approach on a variety of diseases. Finally, the analysis of selected features and corresponding kinases also help the understanding of the potential mechanism of disease-phosphorylation relationships and guide further experimental validations.

Trends in childhood cancer incidence: review of environmental linkages.

PubMed

Buka, Irena; Koranteng, Samuel; Osornio Vargas, Alvaro R

2007-02-01

Cancer in children is rare and accounts for about 1% of all malignancies. In the developed world, however, it is the commonest cause of disease-related deaths in childhood, carrying with it a great economic and emotional cost. Cancers are assumed to be multivariate, multifactorial diseases that occur when a complex and prolonged process involving genetic and environmental factors interact in a multistage sequence. This article explores the available evidence for this process, primarily from the environmental linkages perspective but including some evidence of the genetic factors.

In Silico Approaches and the Role of Ontologies in Aging Research

PubMed Central

Boerries, Melanie; Busch, Hauke; de Grey, Aubrey; Hahn, Udo; Hiller, Thomas; Hoeflich, Andreas; Jansen, Ludger; Janssens, Georges E.; Kaleta, Christoph; Meinema, Anne C.; Schäuble, Sascha; Simm, Andreas; Schofield, Paul N.; Smith, Barry; Sühnel, Juergen; Vera, Julio; Wagner, Wolfgang; Wönne, Eva C.; Wuttke, Daniel

2013-01-01

Abstract The 2013 Rostock Symposium on Systems Biology and Bioinformatics in Aging Research was again dedicated to dissecting the aging process using in silico means. A particular focus was on ontologies, because these are a key technology to systematically integrate heterogeneous information about the aging process. Related topics were databases and data integration. Other talks tackled modeling issues and applications, the latter including talks focused on marker development and cellular stress as well as on diseases, in particular on diseases of kidney and skin. PMID:24188080

Ubiquitination in Periodontal Disease: A Review.

PubMed

Tsuchida, Sachio; Satoh, Mamoru; Takiwaki, Masaki; Nomura, Fumio

2017-07-10

Periodontal disease (periodontitis) is a chronic inflammatory condition initiated by microbial infection that leads to gingival tissue destruction and alveolar bone resorption. The periodontal tissue's response to dental plaque is characterized by the accumulation of polymorphonuclear leukocytes, macrophages, and lymphocytes, all of which release inflammatory mediators and cytokines to orchestrate the immunopathogenesis of periodontal disease. Ubiquitination is achieved by a mechanism that involves a number of factors, including an ubiquitin-activating enzyme, ubiquitin-conjugating enzyme, and ubiquitin-protein ligase. Ubiquitination is a post-translational modification restricted to eukaryotes that are involved in essential host processes. The ubiquitin system has been implicated in the immune response, development, and programmed cell death. Increasing numbers of recent reports have provided evidence that many approaches are delivering promising reports for discovering the relationship between ubiquitination and periodontal disease. The scope of this review was to investigate recent progress in the discovery of ubiquitinated protein in diseased periodontium and to discuss the ubiquitination process in periodontal diseases.

Ubiquitination in Periodontal Disease: A Review

PubMed Central

Tsuchida, Sachio; Satoh, Mamoru; Takiwaki, Masaki; Nomura, Fumio

2017-01-01

Periodontal disease (periodontitis) is a chronic inflammatory condition initiated by microbial infection that leads to gingival tissue destruction and alveolar bone resorption. The periodontal tissue’s response to dental plaque is characterized by the accumulation of polymorphonuclear leukocytes, macrophages, and lymphocytes, all of which release inflammatory mediators and cytokines to orchestrate the immunopathogenesis of periodontal disease. Ubiquitination is achieved by a mechanism that involves a number of factors, including an ubiquitin-activating enzyme, ubiquitin-conjugating enzyme, and ubiquitin–protein ligase. Ubiquitination is a post-translational modification restricted to eukaryotes that are involved in essential host processes. The ubiquitin system has been implicated in the immune response, development, and programmed cell death. Increasing numbers of recent reports have provided evidence that many approaches are delivering promising reports for discovering the relationship between ubiquitination and periodontal disease. The scope of this review was to investigate recent progress in the discovery of ubiquitinated protein in diseased periodontium and to discuss the ubiquitination process in periodontal diseases. PMID:28698506

Gender Differences in Drug Use, Sexually Transmitted Diseases, and Risky Sexual Behavior among Arrested Youths

ERIC Educational Resources Information Center

Dembo, Richard; Belenko, Steven; Childs, Kristina; Greenbaum, Paul E.; Wareham, Jennifer

2010-01-01

Data was collected on arrested youths processed at a centralized intake facility, including youths released back to the community and those placed in secure detention. This article reports the results of a test of a structural model involving newly arrested male and female youths' sexually transmitted diseases (STD) test results, urine analysis…

Behavioral Relaxation Training for Parkinson's Disease Related Dyskinesia and Comorbid Social Anxiety

ERIC Educational Resources Information Center

Lundervold, Duane A.; Pahwa, Rajesh; Lyons, Kelly E.

2013-01-01

Effects of brief Behavioral Relaxation Training (BRT) on anxiety and dyskinesia of a 57-year-old female, with an 11-year history of Parkinson's disease (PD) and 18-months post-deep brain stimulation of the subthalamic nucleus, were evaluated. Multiple process and outcome measures were used including the Clinical Anxiety Scale (CAS), Subjective…

Abnormal Glucose Metabolism in Alzheimer’s Disease: Relation to Autophagy/Mitophagy and Therapeutic Approaches

PubMed Central

Banerjee, Kalpita; Munshi, Soumyabrata; Frank, David E.; Gibson, Gary E.

2015-01-01

Diminished glucose metabolism accompanies many neurodegenerative diseases including Alzheimer’s disease. An understanding of the relation of these metabolic changes to the disease will enable development of novel therapeutic strategies. Following a metabolic challenge, cells generally conserve energy to preserve viability. This requires activation of many cellular repair/regenerative processes such as mitophagy/autophagy and fusion/fission. These responses may diminish cell function in the long term. Prolonged fission induces mitophagy/autophagy which promotes repair but if prolonged progresses to mitochondrial degradation. Abnormal glucose metabolism alters protein signaling including the release of proteins from the mitochondria or migration of proteins from the cytosol to the mitochondria or nucleus. This overview provides an insight into the different mechanisms of autophagy/mitophagy and mitochondrial dynamics in response to the diminished metabolism that occurs with diseases, especially neurodegenerative diseases such as Alzheimer's disease. The review discusses multiple aspects of mitochondrial responses including different signaling proteins and pathways of mitophagy and mitochondrial biogenesis. Improving cellular bioenergetics and mitochondrial dynamics will alter protein signaling and improve cellular/mitochondrial repair and regeneration. An understanding of these changes will suggest new therapeutic strategies. PMID:26077923

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

Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach.

PubMed

Park, Sa-Yoon; Park, Ji-Hun; Kim, Hyo-Su; Lee, Choong-Yeol; Lee, Hae-Jeung; Kang, Ki Sung; Kim, Chang-Eop

2018-01-01

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng , it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng , a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Expression profiling of cardiovascular disease

PubMed Central

2004-01-01

Cardiovascular disease is the most important cause of morbidity and mortality in developed countries, causing twice as many deaths as cancer in the USA. The major cardiovascular diseases, including coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF) and common congenital heart disease (CHD), are caused by multiple genetic and environmental factors, as well as the interactions between them. The underlying molecular pathogenic mechanisms for these disorders are still largely unknown, but gene expression may play a central role in the development and progression of cardiovascular disease. Microarrays are high-throughput genomic tools that allow the comparison of global expression changes in thousands of genes between normal and diseased cells/tissues. Microarrays have recently been applied to CAD/MI, CHF and CHD to profile changes in gene expression patterns in diseased and non-diseased patients. This same technology has also been used to characterise endothelial cells, vascular smooth muscle cells and inflammatory cells, with or without various treatments that mimic disease processes involved in CAD/MI. These studies have led to the identification of unique subsets of genes associated with specific diseases and disease processes. Ongoing microarray studies in the field will provide insights into the molecular mechanism of cardiovascular disease and may generate new diagnostic and therapeutic markers. PMID:15588496

[Psychosocial analysis of the health-disease process].

PubMed

Sawaia, B B

1994-04-01

This article is a reflection about the transdisciplinary paradigmas of the health-illness process noting the symbolic mediation between the reactions of the biological organism and the socio-environment factors including the pathogenic ones. The symbolic-affective mediation is analyzed from the perspective of Social Representation theory allowing one to comprehend the references of individual and collective actions in the health-illness process.

Difficulty Processing Temporary Syntactic Ambiguities in Lewy Body Spectrum Disorder

ERIC Educational Resources Information Center

Grossman, Murray; Gross, Rachel G.; Moore, Peachie; Dreyfuss, Michael; McMillan, Corey T.; Cook, Philip A.; Ash, Sherry; Siderowf, Andrew

2012-01-01

While grammatical aspects of language are preserved, executive deficits are prominent in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's dementia (PDD) and dementia with Lewy bodies (DLB). We examined executive control during sentence processing in LBSD by assessing temporary structural ambiguities. Using an…

Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease

PubMed Central

Fernandez-Prado, Raul; Esteras, Raquel; Perez-Gomez, Maria Vanessa; Gracia-Iguacel, Carolina; Gonzalez-Parra, Emilio; Sanz, Ana B.; Ortiz, Alberto; Sanchez-Niño, Maria Dolores

2017-01-01

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes. PMID:28498348

Nutrients Turned into Toxins: Microbiota Modulation of Nutrient Properties in Chronic Kidney Disease.

PubMed

Fernandez-Prado, Raul; Esteras, Raquel; Perez-Gomez, Maria Vanessa; Gracia-Iguacel, Carolina; Gonzalez-Parra, Emilio; Sanz, Ana B; Ortiz, Alberto; Sanchez-Niño, Maria Dolores

2017-05-12

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes.

[Cormorbidity in multiple sclerosis and its therapeutic approach].

PubMed

Estruch, Bonaventura Casanova

2014-12-01

Multiple sclerosis (MS) is a long-term chronic disease, in which intercurrent processes develop three times more frequently in affected individuals than in persons without MS. Knowledge of the comorbidity of MS, its definition and measurement (Charlson index) improves patient management. Acting on comorbid conditions delays the progression of disability, which is intimately linked to the number of concurrent processes and with health states and habits. Moreover, the presence of comorbidities delays the diagnosis of MS, which in turn delays the start of treatment. The main comorbidity found in MS includes other autoimmune diseases (thyroiditis, systemic lupus erythematosus, or pemphigus) but can also include general diseases, such as asthma or osteomuscular alterations, and, in particular, psychiatric disturbances. All these alterations should be evaluated with multidimensional scales (Disability Expectancy Table, DET), which allow more accurate determination of the patient's real clinical course and quality of life. These scales also allow identification of how MS, concurrent and intercurrent processes occurring during the clinical course, and the treatment provided affect patients with MS. An overall approach to patients' health status helps to improve quality of life. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Complement in the Initiation and Evolution of Rheumatoid Arthritis

PubMed Central

Holers, V. Michael; Banda, Nirmal K.

2018-01-01

The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA. PMID:29892280

Bioactive Nutrients and Nutrigenomics in Age-Related Diseases.

PubMed

Rescigno, Tania; Micolucci, Luigina; Tecce, Mario F; Capasso, Anna

2017-01-08

The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the "omics" technologies (transcriptomics, proteomics and metabolomics) are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

MR Imaging of the Penis and Scrotum.

PubMed

Parker, Rex A; Menias, Christine O; Quazi, Robin; Hara, Amy K; Verma, Sadhna; Shaaban, Akram; Siegel, Cary L; Radmanesh, Alireza; Sandrasegaran, Kumar

2015-01-01

Traditionally, due to its low cost, ready availability, and proved diagnostic accuracy, ultrasonography (US) has been the primary imaging modality for the evaluation of scrotal and, to a lesser extent, penile disease. However, US is limited by its relatively small useful field of view, operator dependence, and inability to provide much information on tissue characterization. Magnetic resonance (MR) imaging, with its excellent soft-tissue contrast and good spatial resolution, is increasingly being used as both a problem-solving tool in patients who have already undergone US and as a primary modality for the evaluation of suspected disease. Specifically, MR imaging can aid in differentiating between benign and malignant lesions seen at US, help define the extent of inflammatory processes or traumatic injuries, and play a vital role in locoregional staging of tumors. Consequently, it is becoming more important for radiologists to be familiar with the wide range of penile and scrotal disease entities and their MR imaging appearances. The authors review the basic anatomy of the penis and scrotum as seen at MR imaging and provide a basic protocol for penile and scrotal imaging, with emphasis on the advantages of MR imaging. Pathologic processes are organized into traumatic (including penile fracture and contusion), infectious or inflammatory (including Fournier gangrene and scrotal abscess), and neoplastic (including both benign and malignant scrotal and penile tumors) processes. ©RSNA, 2015.

The Role and Immunobiology of Eosinophils in the Respiratory System: a Comprehensive Review.

PubMed

Eng, Stephanie S; DeFelice, Magee L

2016-04-01

The eosinophil is a fully delineated granulocyte that disseminates throughout the bloodstream to end-organs after complete maturation in the bone marrow. While the presence of eosinophils is not uncommon even in healthy individuals, these granulocytes play a central role in inflammation and allergic processes. Normally appearing in smaller numbers, higher levels of eosinophils in the peripheral blood or certain tissues typically signal a pathologic process. Eosinophils confer a beneficial effect on the host by enhancing immunity against molds and viruses. However, tissue-specific elevation of eosinophils, particularly in the respiratory system, can cause a variety of short-term symptoms and may lead to long-term sequelae. Eosinophils often play a role in more commonly encountered disease processes, such as asthma and allergic responses in the upper respiratory tract. They are also integral in the pathology of less common diseases including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and drug reaction with eosinophilia and systemic symptoms. They can be seen in neoplastic disorders or occupational exposures as well. The involvement of eosinophils in pulmonary disease processes can affect the method of diagnosis and the selection of treatment modalities. By analyzing the complex interaction between the eosinophil and its environment, which includes signaling molecules and tissues, different therapies have been discovered and created in order to target disease processes at a cellular level. Innovative treatments such as mepolizumab and benralizumab will be discussed. The purpose of this article is to further explore the topic of eosinophilic presence, activity, and pathology in the respiratory tract, as well as discuss current and future treatment options through a detailed literature review.

Review on iron and its importance for human health

PubMed Central

Abbaspour, Nazanin; Hurrell, Richard; Kelishadi, Roya

2014-01-01

It is well-known that deficiency or over exposure to various elements has noticeable effects on human health. The effect of an element is determined by several characteristics, including absorption, metabolism, and degree of interaction with physiological processes. Iron is an essential element for almost all living organisms as it participates in a wide variety of metabolic processes, including oxygen transport, deoxyribonucleic acid (DNA) synthesis, and electron transport. However, as iron can form free radicals, its concentration in body tissues must be tightly regulated because in excessive amounts, it can lead to tissue damage. Disorders of iron metabolism are among the most common diseases of humans and encompass a broad spectrum of diseases with diverse clinical manifestations, ranging from anemia to iron overload, and possibly to neurodegenerative diseases. In this review, we discuss the latest progress in studies of iron metabolism and bioavailability, and our current understanding of human iron requirement and consequences and causes of iron deficiency. Finally, we discuss strategies for prevention of iron deficiency. PMID:24778671

The impact of Parkinson's disease and subthalamic deep brain stimulation on reward processing.

PubMed

Evens, Ricarda; Stankevich, Yuliya; Dshemuchadse, Maja; Storch, Alexander; Wolz, Martin; Reichmann, Heinz; Schlaepfer, Thomas E; Goschke, Thomas; Lueken, Ulrike

2015-08-01

Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation of the STN (DBS-STN) in patients with idiopathic Parkinson's disease (PD). We compared 33 PD patients treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33 PD patients without DBS, but optimized pharmacological treatment and 34 age-matched healthy controls. We then investigated DBS-STN effects using a postoperative stimulation-on/ -off design. The task set included a delay discounting task, a task to assess changes in incentive salience attribution, and the Iowa Gambling Task. The presence of PD was associated with increased incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN increased risky choices in the Iowa Gambling Task under DBS-on condition, but did not further affect incentive salience attribution or the evaluation of delayed rewards. Findings indicate that acute DBS-STN affects specific aspects of reward processing, including the weighting of gains and losses, while larger-scale effects of disease or medication are predominant in others reward-related functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling congenital disease and inborn errors of development in Drosophila melanogaster

PubMed Central

Moulton, Matthew J.; Letsou, Anthea

2016-01-01

ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes. PMID:26935104

[Transitions in context: findings related to rural-to-urban migration and chronic non-communicable diseases in Peru].

PubMed

Miranda, J Jaime; Wells, Jonathan C K; Smeeth, Liam

2012-01-01

In order to better understand the emergence of chronic non-communicable diseases in low- and middle-income countries this article seeks to present, in context, different transitional processes which societies and populations are currently undergoing. Relevant factors for specific contexts such as Peru are described, including internal migration, urbanization and profiles of adversity in early life, all of them linked to chronic non-communicable diseases, including obesity and overweight. The capacity-load model, which considers chronic disease risk in adulthood as a function of two generic traits, metabolic capacity and metabolic load, is described. The contribution of rural-to-urban migration to this problem is also presented. Finally, these topics are framed within pending challenges for public health in Peru.

Challenges in orphan drug development and regulatory policy in China.

PubMed

Cheng, Alice; Xie, Zhi

2017-01-18

While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.

Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease.

PubMed

German, Christopher L; Baladi, Michelle G; McFadden, Lisa M; Hanson, Glen R; Fleckenstein, Annette E

2015-10-01

Dopamine (DA) plays a well recognized role in a variety of physiologic functions such as movement, cognition, mood, and reward. Consequently, many human disorders are due, in part, to dysfunctional dopaminergic systems, including Parkinson's disease, attention deficit hyperactivity disorder, and substance abuse. Drugs that modify the DA system are clinically effective in treating symptoms of these diseases or are involved in their manifestation, implicating DA in their etiology. DA signaling and distribution are primarily modulated by the DA transporter (DAT) and by vesicular monoamine transporter (VMAT)-2, which transport DA into presynaptic terminals and synaptic vesicles, respectively. These transporters are regulated by complex processes such as phosphorylation, protein-protein interactions, and changes in intracellular localization. This review provides an overview of 1) the current understanding of DAT and VMAT2 neurobiology, including discussion of studies ranging from those conducted in vitro to those involving human subjects; 2) the role of these transporters in disease and how these transporters are affected by disease; and 3) and how selected drugs alter the function and expression of these transporters. Understanding the regulatory processes and the pathologic consequences of DAT and VMAT2 dysfunction underlies the evolution of therapeutic development for the treatment of DA-related disorders. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease

PubMed Central

German, Christopher L.; Baladi, Michelle G.; McFadden, Lisa M.; Hanson, Glen R.

2015-01-01

Dopamine (DA) plays a well recognized role in a variety of physiologic functions such as movement, cognition, mood, and reward. Consequently, many human disorders are due, in part, to dysfunctional dopaminergic systems, including Parkinson’s disease, attention deficit hyperactivity disorder, and substance abuse. Drugs that modify the DA system are clinically effective in treating symptoms of these diseases or are involved in their manifestation, implicating DA in their etiology. DA signaling and distribution are primarily modulated by the DA transporter (DAT) and by vesicular monoamine transporter (VMAT)-2, which transport DA into presynaptic terminals and synaptic vesicles, respectively. These transporters are regulated by complex processes such as phosphorylation, protein–protein interactions, and changes in intracellular localization. This review provides an overview of 1) the current understanding of DAT and VMAT2 neurobiology, including discussion of studies ranging from those conducted in vitro to those involving human subjects; 2) the role of these transporters in disease and how these transporters are affected by disease; and 3) and how selected drugs alter the function and expression of these transporters. Understanding the regulatory processes and the pathologic consequences of DAT and VMAT2 dysfunction underlies the evolution of therapeutic development for the treatment of DA-related disorders. PMID:26408528

Computerized clinical decision support systems for chronic disease management: a decision-maker-researcher partnership systematic review.

PubMed

Roshanov, Pavel S; Misra, Shikha; Gerstein, Hertzel C; Garg, Amit X; Sebaldt, Rolf J; Mackay, Jean A; Weise-Kelly, Lorraine; Navarro, Tamara; Wilczynski, Nancy L; Haynes, R Brian

2011-08-03

The use of computerized clinical decision support systems (CCDSSs) may improve chronic disease management, which requires recurrent visits to multiple health professionals, ongoing disease and treatment monitoring, and patient behavior modification. The objective of this review was to determine if CCDSSs improve the processes of chronic care (such as diagnosis, treatment, and monitoring of disease) and associated patient outcomes (such as effects on biomarkers and clinical exacerbations). We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for potentially eligible articles published up to January 2010. We included randomized controlled trials that compared the use of CCDSSs to usual practice or non-CCDSS controls. Trials were eligible if at least one component of the CCDSS was designed to support chronic disease management. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of relevant outcomes. Of 55 included trials, 87% (n = 48) measured system impact on the process of care and 52% (n = 25) of those demonstrated statistically significant improvements. Sixty-five percent (36/55) of trials measured impact on, typically, non-major (surrogate) patient outcomes, and 31% (n = 11) of those demonstrated benefits. Factors of interest to decision makers, such as cost, user satisfaction, system interface and feature sets, unique design and deployment characteristics, and effects on user workflow were rarely investigated or reported. A small majority (just over half) of CCDSSs improved care processes in chronic disease management and some improved patient health. Policy makers, healthcare administrators, and practitioners should be aware that the evidence of CCDSS effectiveness is limited, especially with respect to the small number and size of studies measuring patient outcomes.

Computerized clinical decision support systems for chronic disease management: A decision-maker-researcher partnership systematic review

PubMed Central

2011-01-01

Background The use of computerized clinical decision support systems (CCDSSs) may improve chronic disease management, which requires recurrent visits to multiple health professionals, ongoing disease and treatment monitoring, and patient behavior modification. The objective of this review was to determine if CCDSSs improve the processes of chronic care (such as diagnosis, treatment, and monitoring of disease) and associated patient outcomes (such as effects on biomarkers and clinical exacerbations). Methods We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for potentially eligible articles published up to January 2010. We included randomized controlled trials that compared the use of CCDSSs to usual practice or non-CCDSS controls. Trials were eligible if at least one component of the CCDSS was designed to support chronic disease management. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of relevant outcomes. Results Of 55 included trials, 87% (n = 48) measured system impact on the process of care and 52% (n = 25) of those demonstrated statistically significant improvements. Sixty-five percent (36/55) of trials measured impact on, typically, non-major (surrogate) patient outcomes, and 31% (n = 11) of those demonstrated benefits. Factors of interest to decision makers, such as cost, user satisfaction, system interface and feature sets, unique design and deployment characteristics, and effects on user workflow were rarely investigated or reported. Conclusions A small majority (just over half) of CCDSSs improved care processes in chronic disease management and some improved patient health. Policy makers, healthcare administrators, and practitioners should be aware that the evidence of CCDSS effectiveness is limited, especially with respect to the small number and size of studies measuring patient outcomes. PMID:21824386

Oxidative injury of the pulmonary circulation in the perinatal period: Short- and long-term consequences for the human cardiopulmonary system

PubMed Central

de Wijs-Meijler, Daphne P.; Duncker, Dirk J.; Tibboel, Dick; Schermuly, Ralph T.; Weissmann, Norbert; Merkus, Daphne; Reiss, Irwin K.M.

2017-01-01

Development of the pulmonary circulation is a complex process with a spatial pattern that is tightly controlled. This process is vulnerable for disruption by various events in the prenatal and early postnatal periods. Disruption of normal pulmonary vascular development leads to abnormal structure and function of the lung vasculature, causing neonatal pulmonary vascular diseases. Premature babies are especially at risk of the development of these diseases, including persistent pulmonary hypertension and bronchopulmonary dysplasia. Reactive oxygen species play a key role in the pathogenesis of neonatal pulmonary vascular diseases and can be caused by hyperoxia, mechanical ventilation, hypoxia, and inflammation. Besides the well-established short-term consequences, exposure of the developing lung to injurious stimuli in the perinatal period, including oxidative stress, may also contribute to the development of pulmonary vascular diseases later in life, through so-called “fetal or perinatal programming.” Because of these long-term consequences, it is important to develop a follow-up program tailored to adolescent survivors of neonatal pulmonary vascular diseases, aimed at early detection of adult pulmonary vascular diseases, and thereby opening the possibility of early intervention and interfering with disease progression. This review focuses on pathophysiologic events in the perinatal period that have been shown to disrupt human normal pulmonary vascular development, leading to neonatal pulmonary vascular diseases that can extend even into adulthood. This knowledge may be particularly important for ex-premature adults who are at risk of the long-term consequences of pulmonary vascular diseases, thereby contributing disproportionately to the burden of adult cardiovascular disease in the future. PMID:28680565

Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases?

PubMed

Iida, Tomoya; Wagatsuma, Kohei; Hirayama, Daisuke; Nakase, Hiroshi

2017-12-21

Osteopontin (OPN) is involved in a variety of biological processes, including bone remodeling, innate immunity, acute and chronic inflammation, and cancer. The expression of OPN occurs in various tissues and cells, including intestinal epithelial cells and immune cells such as macrophages, dendritic cells, and T lymphocytes. OPN plays an important role in the efficient development of T helper 1 immune responses and cell survival by inhibiting apoptosis. The association of OPN with apoptosis has been investigated. In this review, we described the role of OPN in inflammatory gastrointestinal and liver diseases, focusing on the association of OPN with apoptosis. OPN changes its association with apoptosis depending on the type of disease and the phase of disease activity, acting as a promoter or a suppressor of inflammation and inflammatory carcinogenesis. It is essential that the roles of OPN in those diseases are elucidated, and treatments based on its mechanism are developed.

The past, current and future of diagnosis and management of pleural disease

PubMed Central

2015-01-01

Pleural disease is frequently encountered by the chest physician. Pleural effusions arise as the sequelae of underlying disease processes including pressure/volume imbalances, infection and malignancy. In addition to pleural effusions, persistent air leaks after surgery and bronchopleural fistulae remain a challenge. Our understanding of pleural disease including its diagnosis and management, have made tremendous strides. The introduction of the molecular detection of organism specific infection, risk stratification and improvements in the non-surgical treatment of patients with pleural infection are all within reach and may be the standard of care in the very near future. Malignant pleural effusion management continues to evolve with the introduction of tunneled pleural catheters and procedures combining that and chemical pleurodesis. These advances in the diagnostic and therapeutic evaluation of pleural disease as well as what seems to be an increasing multidisciplinary interest in the space foretell a bright future. PMID:26807281

A saponin-detoxifying enzyme mediates suppression of plant defences

NASA Astrophysics Data System (ADS)

Bouarab, K.; Melton, R.; Peart, J.; Baulcombe, D.; Osbourn, A.

2002-08-01

Plant disease resistance can be conferred by constitutive features such as structural barriers or preformed antimicrobial secondary metabolites. Additional defence mechanisms are activated in response to pathogen attack and include localized cell death (the hypersensitive response). Pathogens use different strategies to counter constitutive and induced plant defences, including degradation of preformed antimicrobial compounds and the production of molecules that suppress induced plant defences. Here we present evidence for a two-component process in which a fungal pathogen subverts the preformed antimicrobial compounds of its host and uses them to interfere with induced defence responses. Antimicrobial saponins are first hydrolysed by a fungal saponin-detoxifying enzyme. The degradation product of this hydrolysis then suppresses induced defence responses by interfering with fundamental signal transduction processes leading to disease resistance.

Current Dilemmas in Defining the Boundaries of Disease.

PubMed

Doust, Jenny; Jean Walker, Mary; Rogers, Wendy A

2017-08-01

Boorse's biostatistical theory states that diseases should be defined in ways that reflect disturbances of biological function and that are objective and value free. We use three examples from contemporary medicine that demonstrate the complex issues that arise when defining the boundaries of disease: polycystic ovary syndrome, chronic kidney disease, and myocardial infarction. We argue that the biostatistical theory fails to provide sufficient guidance on where the boundaries of disease should be drawn, contains ambiguities relating to choice of reference class, and is out of step with medical processes for identifying disease boundaries. Although proponents of the biostatistical theory might regard these practical issues as irrelevant to the aim of providing a theoretical account of disease, we take them to indicate the need for a theoretical account that is adequate for current needs-including limiting new forms of medicalization that are driven by the identification of disease based on dysfunction. Our processes for determining the boundaries for disease need to recognize that there is no value-free method for making these decisions. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Susceptibility based upon Chemical Interaction with Disease ...

EPA Pesticide Factsheets

One of the challenges facing toxicology and risk assessment is that numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest is the potential for chemicals to interact with background aging and disease processes, an interaction that may yield cumulative damage, altered chemical potency, and increased disease incidence. This review outlines the interactions possible between chemicals and background disease and identifies the type of information needed to evaluate such interactions. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which allows the identification of vulnerable individuals based upon the level of risk biomarker. The impact of toxic chemicals on this biomarker can then be used to predict how the chemical modifies disease risk as long as related mechanistic and toxicological data are consistent with toxicant effect on the disease process. Several case studies are briefly presented which describe the toxic chemical, the clinical biomarker and the impacted disease including: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration rate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; trichloroethylene/increased anti-nuclear antibody/autoimmunity; dioxin/increased CYP1A1/hypertension. These case studies point o

Rare Disease Mechanisms Identified by Genealogical Proteomics of Copper Homeostasis Mutant Pedigrees.

PubMed

Zlatic, Stephanie A; Vrailas-Mortimer, Alysia; Gokhale, Avanti; Carey, Lucas J; Scott, Elizabeth; Burch, Reid; McCall, Morgan M; Rudin-Rush, Samantha; Davis, John Bowen; Hartwig, Cortnie; Werner, Erica; Li, Lian; Petris, Michael; Faundez, Victor

2018-03-28

Rare neurological diseases shed light onto universal neurobiological processes. However, molecular mechanisms connecting genetic defects to their disease phenotypes are elusive. Here, we obtain mechanistic information by comparing proteomes of cells from individuals with rare disorders with proteomes from their disease-free consanguineous relatives. We use triple-SILAC mass spectrometry to quantify proteomes from human pedigrees affected by mutations in ATP7A, which cause Menkes disease, a rare neurodegenerative and neurodevelopmental disorder stemming from systemic copper depletion. We identified 214 proteins whose expression was altered in ATP7A -/y fibroblasts. Bioinformatic analysis of ATP7A-mutant proteomes identified known phenotypes and processes affected in rare genetic diseases causing copper dyshomeostasis, including altered mitochondrial function. We found connections between copper dyshomeostasis and the UCHL1/PARK5 pathway of Parkinson disease, which we validated with mitochondrial respiration and Drosophila genetics assays. We propose that our genealogical "omics" strategy can be broadly applied to identify mechanisms linking a genomic locus to its phenotypes. Copyright © 2018 Elsevier Inc. All rights reserved.

Pathogenesis of the limb manifestations and exercise limitations in peripheral artery disease.

PubMed

Hiatt, William R; Armstrong, Ehrin J; Larson, Christopher J; Brass, Eric P

2015-04-24

Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease. © 2015 American Heart Association, Inc.

Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents.

PubMed

Krzewska, Aleksandra; Ben-Skowronek, Iwona

2016-01-01

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases developing in childhood. The incidence of the disease in children increases for unknown reasons at a rate from 3 to 5% every year worldwide. The background of T1DM is associated with the autoimmune process of pancreatic beta cell destruction, which leads to absolute insulin deficiency and organ damage. Complex interactions between environmental and genetic factors contribute to the development of T1DM in genetically predisposed patients. The T1DM-inducing autoimmune process can also affect other organs, resulting in development of additional autoimmune diseases in the patient, thereby impeding diabetes control. The most common T1DM comorbidities include autoimmune thyroid diseases, celiac disease, and autoimmune gastritis; additionally, diabetes can be a component of PAS (Polyglandular Autoimmune Syndrome). The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T1DM. We also present suggestions concerning screening tests.

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research

PubMed Central

McCann, Liza J; Pilkington, Clarissa A; Huber, Adam M; Ravelli, Angelo; Appelbe, Duncan; Kirkham, Jamie J; Williamson, Paula R; Aggarwal, Amita; Christopher-Stine, Lisa; Constantin, Tamas; Feldman, Brian M; Lundberg, Ingrid; Maillard, Sue; Mathiesen, Pernille; Murphy, Ruth; Pachman, Lauren M; Reed, Ann M; Rider, Lisa G; van Royen-Kerkof, Annet; Russo, Ricardo; Spinty, Stefan; Wedderburn, Lucy R

2018-01-01

Objectives This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres. Methods A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation. Results A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter. Conclusions Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases. PMID:29084729

Calcium in the pathomechanism of amyotrophic lateral sclerosis - Taking center stage?

PubMed

Patai, Roland; Nógrádi, Bernát; Engelhardt, József I; Siklós, László

2017-02-19

Amyotrophic lateral sclerosis is an incurable, relentlessly progressive disease primarily affecting motor neurons. The cause of the disease, except for the mutations identified in a small fraction of patients, is unknown. The major mechanisms contributing to the degeneration of motor neurons have already been disclosed and characterized, including excitotoxicity, oxidative stress, mitochondrial dysfunction, and immune/inflammatory processes. During the progression of the disease these toxic processes are not discrete, but each facilitates the deleterious effect of the other. However, due to their common reciprocal calcium dependence, calcium ions may act as a common denominator and through a positive feedback loop may combine the individual pathological processes into a unified escalating mechanism of neuronal destruction. This mini-review provides an overview of the mutual calcium dependence of the major toxic mechanisms associated with amyotrophic lateral sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Imaging of musculoskeletal manifestations in sickle cell disease patients.

PubMed

Kosaraju, Vijaya; Harwani, Alok; Partovi, Sasan; Bhojwani, Nicholas; Garg, Vasant; Ayyappan, Sabarish; Kosmas, Christos; Robbin, Mark

2017-05-01

Sickle cell disease (SCD) is a hereditary red cell disorder with clinical manifestations secondary to sickling or crescent-shaped distortion of the red blood cells. Major clinical manifestations of SCD include haemolytic anaemia and vaso-occlusive phenomena resulting in ischaemic tissue injury and organ damage. Chronic sequelae of the anaemia and vaso-occlusive processes involving the musculoskeletal system include complications related to extramedullary haematopoiesis, osteonecrosis, myonecrosis and osteomyelitis. Sickle cell bone disease is one of the commonest clinical presentations. Awareness and knowledge of the imaging features related to these complications are essential for early diagnosis and prompt management. In this article, the pathophysiology and key imaging findings related to these complications are reviewed.

Alternative Polyadenylation in Human Diseases

PubMed Central

Chang, Jae-Woong; Yeh, Hsin-Sung

2017-01-01

Varying length of messenger RNA (mRNA) 3′-untranslated region is generated by alternating the usage of polyadenylation sites during pre-mRNA processing. It is prevalent through all eukaryotes and has emerged as a key mechanism for controlling gene expression. Alternative polyadenylation (APA) plays an important role for cell growth, proliferation, and differentiation. In this review, we discuss the functions of APA related with various physiological conditions including cellular metabolism, mRNA processing, and protein diversity in a variety of disease models. We also discuss the molecular mechanisms underlying APA regulation, such as variations in the concentration of mRNA processing factors and RNA-binding proteins, as well as global transcriptome changes under cellular signaling pathway. PMID:29271615

Dental caries and pulpal disease.

PubMed

Zero, Domenick T; Zandona, Andrea Ferreira; Vail, Mychel Macapagal; Spolnik, Kenneth J

2011-01-01

This article reviews the diagnostic process, from the first clinically evident stages of the caries process to development of pulpal pathosis. The caries diagnostic process includes 4 interconnected components-staging caries lesion severity, assessing caries lesion activity, and risk assessments at the patient and tooth surface level - which modify treatment decisions for the patient. Pulpal pathosis is diagnosed as reversible pulpitis, irreversible pulpitis (asymptomatic), irreversible pulpitis (symptomatic), and pulp necrosis. Periapical disease is diagnosed as symptomatic apical periodontitis, asymptomatic apical periodontitis, acute apical abscess, and chronic apical abscess. Ultimately, the goal of any diagnosis should be to achieve better treatment decisions and health outcomes for the patient. Copyright © 2011 Elsevier Inc. All rights reserved.

Vicious circles in inflammatory bowel disease.

PubMed

Sonnenberg, Amnon; Collins, Judith F

2006-10-01

Inflammatory bowel disease can present with a bewildering array of disease manifestations whose overall impact on patient health is difficult to disentangle. The multitude of disease complications and therapeutic side effects result in conflicting ideas on how to best manage a patient. The aim of the study is to test the usefulness of influence diagrams in resolving conflicts centered on managing complex disease processes. The influences of a disease process and the ensuing medical interventions on the health of a patient with inflammatory bowel disease are modeled by an influence diagram. Patient health is the focal point of multiple influences affecting its overall strength. Any downstream influence represents the focal point of other preceding upstream influences. The mathematics underlying the influence diagram is similar to that of a decision tree. Its formalism allows one to consider additive and inhibitory influences and include in the same analysis qualitatively different types of parameters, such as diagnoses, complications, side effects, and therapeutic outcomes. Three exemplary cases are presented to illustrate the potential use of influence diagrams. In all three case scenarios, Crohn's disease resulted in disease manifestations that seemingly interfered with its own therapy. The presence of negative feedback loops rendered the management of each case particularly challenging. The analyses by influence diagrams revealed subtle interactions among the multiple influences and their joint contributions to the patient's overall health that would have been difficult to appreciate by verbal reasoning alone. Influence diagrams represent a decision tool that is particularly suited to improve decision-making in inflammatory bowel disease. They highlight key factors of a complex disease process and help to assess their quantitative interactions.

Harnessing RNA interference to develop neonatal therapies: from Nobel Prize winning discovery to proof of concept clinical trials.

PubMed

DeVincenzo, John P

2009-10-01

A revolution in the understanding of RNA biological processing and control is leading to revolutionary new concepts in human therapeutics. It has become increasingly clear that the so called "non-coding RNA" exerts specific and profound functional control on regulation of protein production and indeed controls the expression of all genes. Harnessing this naturally-occurring RNA-mediated regulation of protein production has immense human therapeutic potential. These processes are collectively known as RNA interference (RNAi). RNAi is a recently discovered, naturally-occurring intracellular process that regulates gene expression through the silencing of specific mRNAs. Methods of harnessing this natural pathway are being developed that allow the catalytic degradation of targeted mRNAs using specifically designed complementary small inhibitory RNAs (siRNA). siRNAs are being chemically modified to acquire drug-like properties. Numerous recent high profile publications have provided proofs of concept that RNA interference may be useful therapeutically. Much of the design of these siRNAs can be accomplished bioinformatically, thus potentially expediting drug discovery and opening new avenues of therapy for many uncommon, orphan, or emerging diseases. This makes this approach very attractive for developing therapies targeting orphan diseases including neonatal diseases. Theoretically, any disease that can be ameliorated through knockdown of any endogenous or exogenous protein is a potential therapeutic target for RNAi-based therapeutics. Lung diseases are particularly attractive targets for RNAi therapeutics since the affected cells' location increases their accessibility to topical administration of siRNA, for example by aerosol. Respiratory viral infections and chronic lung disease are examples of such diseases. RNAi therapeutics have been shown to be active against RSV, parainfluenza and human metapneumoviruses in vitro and in vivo resulting in profound antiviral effects. The first proof of concept test of efficacy of an RNAi-based therapeutic in man has been initiated. A discussion of the science behind RNA interference is followed by a presentation of the potential practical issues in applying this technology to neonatal respiratory viral diseases. RNAi may offer new strategies for the treatment of a variety of orphan diseases including neonatal diseases, RSV infections, and other respiratory viruses.

SWI/SNF Chromatin-remodeling Factors: Multiscale Analyses and Diverse Functions*

PubMed Central

Euskirchen, Ghia; Auerbach, Raymond K.; Snyder, Michael

2012-01-01

Chromatin-remodeling enzymes play essential roles in many biological processes, including gene expression, DNA replication and repair, and cell division. Although one such complex, SWI/SNF, has been extensively studied, new discoveries are still being made. Here, we review SWI/SNF biochemistry; highlight recent genomic and proteomic advances; and address the role of SWI/SNF in human diseases, including cancer and viral infections. These studies have greatly increased our understanding of complex nuclear processes. PMID:22952240

Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

PubMed Central

Mora, Ana L.; Rojas, Mauricio

2017-01-01

Idiopathic pulmonary fibrosis (IPF) is a chronic age-related lung disease with high mortality that is characterized by abnormal scarring of the lung parenchyma. There has been a recent attempt to define the age-associated changes predisposing individuals to develop IPF. Age-related perturbations that are increasingly found in epithelial cells and fibroblasts from IPF lungs compared with age-matched cells from normal lungs include defective autophagy, telomere attrition, altered proteostasis, and cell senescence. These divergent processes seem to converge in mitochondrial dysfunction and metabolic distress, which potentiate maladaptation to stress and susceptibility to age-related diseases such as IPF. Therapeutic approaches that target aging processes may be beneficial for halting the progression of disease and improving quality of life in IPF patients. PMID:28145905

Gene Expression Profile Change and Associated Physiological and Pathological Effects in Mouse Liver Induced by Fasting and Refeeding

PubMed Central

Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

2011-01-01

Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes. PMID:22096593

Gene expression profile change and associated physiological and pathological effects in mouse liver induced by fasting and refeeding.

PubMed

Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

2011-01-01

Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes.

Functional components and medicinal properties of food: a review.

PubMed

Abuajah, Christian Izuchukwu; Ogbonna, Augustine Chima; Osuji, Chijioke Maduka

2015-05-01

Research has proved a relationship between functional components of food, health and well-being. Thus, functional components of food can be effectively applied in the treatment and prevention of diseases. They act simultaneously at different or identical target sites with the potential to impart physiological benefits and promotion of wellbeing including reducing the risk of cancer, cardiovascular disease, osteoporosis, inflammation, type II diabetes, and other chronic degenerative diseases, lowering of blood cholesterol, neutralization of reactive oxygen species and charged radicals, anticarcinogenic effect, low-glycaemic response, etc. Previously, it was thought that functional ingredients such as non-starchy carbohydrates including soluble and insoluble dietary fibres, fucoidan; antioxidants including polyphenols, carotenoids, tocopherols, tocotrienols, phytosterols, isoflavones, organosulphur compounds; plant sterols and soy phytoestrogens occur only in plant foods (whole grains, fruits, and vegetables) as phytochemicals. However, probiotics, prebiotics, conjugated linolenic acid, long-chain omega-3, -6 and -9-polyunsaturated fatty acids, and bioactive peptides have proved that functional components are equally available in animal products such as milk, fermented milk products and cold-water fish. The way a food is processed affects its functional components. Many processing techniques have been found to lower the concentration of functional components in food. Conversely, other techniques were found to increase them. Hence, in a time when the role of a healthy diet in preventing non-communicable diseases is well accepted, the borderline between food and medicine is becoming very thin.

Mechanisms of metabolic memory and renal hypoxia as a therapeutic target in diabetic kidney disease.

PubMed

Hirakawa, Yosuke; Tanaka, Tetsuhiro; Nangaku, Masaomi

2017-05-01

Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is under discussion. Although the term DKD was originally defined as 'kidney disease specific to diabetes,' DKD frequently means chronic kidney disease with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction as a result of nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end-products, deoxyribonucleic acid methylation, histone modifications and non-coding ribonucleic acid including micro ribonucleic acid. Regardless of the presence of diabetes mellitus, the final common pathway in chronic kidney disease is chronic kidney hypoxia, which influences epigenetic processes, including deoxyribonucleic acid methylation, histone modification, and conformational changes in micro ribonucleic acid and chromatin. Therefore, hypoxia and oxidative stress are appropriate targets of therapies against DKD. Prolyl hydroxylase domain inhibitor enhances the defensive mechanisms against hypoxia. Bardoxolone methyl protects against oxidative stress, and can even reverse impaired renal function; a phase 2 trial with considerable attention to heart complications is currently ongoing in Japan. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Retinoic acid signaling pathways in development and diseases.

PubMed

Das, Bhaskar C; Thapa, Pritam; Karki, Radha; Das, Sasmita; Mahapatra, Sweta; Liu, Ting-Chun; Torregroza, Ingrid; Wallace, Darren P; Kambhampati, Suman; Van Veldhuizen, Peter; Verma, Amit; Ray, Swapan K; Evans, Todd

2014-01-15

Retinoids comprise a group of compounds each composed of three basic parts: a trimethylated cyclohexene ring that is a bulky hydrophobic group, a conjugated tetraene side chain that functions as a linker unit, and a polar carbon-oxygen functional group. Biochemical conversion of carotenoid or other retinoids to retinoic acid (RA) is essential for normal regulation of a wide range of biological processes including development, differentiation, proliferation, and apoptosis. Retinoids regulate various physiological outputs by binding to nuclear receptors called retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which themselves are DNA-binding transcriptional regulators. The functional response of RA and their receptors are modulated by a host of coactivators and corepressors. Retinoids are essential in the development and function of several organ systems; however, deregulated retinoid signaling can contribute to serious diseases. Several natural and synthetic retinoids are in clinical use or undergoing trials for treating specific diseases including cancer. In this review, we provide a broad overview on the importance of retinoids in development and various diseases, highlighting various retinoids in the drug discovery process, ranging all the way from retinoid chemistry to clinical uses and imaging. Copyright © 2013 Elsevier Ltd. All rights reserved.

Motor Control Abnormalities in Parkinson’s Disease

PubMed Central

Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

2012-01-01

The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

Dietary polyphenols and chromatin remodeling.

PubMed

Russo, Gian Luigi; Vastolo, Viviana; Ciccarelli, Marco; Albano, Luigi; Macchia, Paolo Emidio; Ungaro, Paola

2017-08-13

Polyphenols are the most abundant phytochemicals in fruits, vegetables, and plant-derived beverages. Recent findings suggest that polyphenols display the ability to reverse adverse epigenetic regulation involved in pathological conditions, such as obesity, metabolic disorder, cardiovascular and neurodegenerative diseases, and various forms of cancer. Epigenetics, defined as heritable changes to the transcriptome, independent from those occurring in the genome, includes DNA methylation, histone modifications, and posttranscriptional gene regulation by noncoding RNAs. Sinergistically and cooperatively, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Such induced epigenetic changes can be inherited during cell division, resulting in permanent maintenance of the acquired phenotype, but they may also occur throughout an individual life-course and may ultimately influence phenotypic outcomes (health and disease risk). In the last decade, a number of studies have shown that nutrients can affect metabolic traits by altering the structure of chromatin and directly regulate both transcription and translational processes. In this context, dietary polyphenol-targeted epigenetics becomes an attractive approach for disease prevention and intervention. Here, we will review how polyphenols, including flavonoids, curcuminoids, and stilbenes, modulate the establishment and maintenance of key epigenetic marks, thereby influencing gene expression and, hence, disease risk and health.

Hormesis and medicine

PubMed Central

Calabrese, Edward J

2008-01-01

Evidence is presented which supports the conclusion that the hormetic dose–response model is the most common and fundamental in the biological and biomedical sciences, being highly generalizable across biological model, endpoint measured and chemical class and physical agent. The paper provides a broad spectrum of applications of the hormesis concept for clinical medicine including anxiety, seizure, memory, stroke, cancer chemotherapy, dermatological processes such as hair growth, osteoporosis, ocular diseases, including retinal detachment, statin effects on cardiovascular function and tumour development, benign prostate enlargement, male sexual behaviours/dysfunctions, and prion diseases. PMID:18662293

Community resources and technologies developed through the NIH Roadmap Epigenomics Program.

PubMed

Satterlee, John S; Beckel-Mitchener, Andrea; McAllister, Kim; Procaccini, Dena C; Rutter, Joni L; Tyson, Frederick L; Chadwick, Lisa Helbling

2015-01-01

This chapter describes resources and technologies generated by the NIH Roadmap Epigenomics Program that may be useful to epigenomics researchers investigating a variety of diseases including cancer. Highlights include reference epigenome maps for a wide variety of human cells and tissues, the development of new technologies for epigenetic assays and imaging, the identification of novel epigenetic modifications, and an improved understanding of the role of epigenetic processes in a diversity of human diseases. We also discuss future needs in this area including exploration of epigenomic variation between individuals, single-cell epigenomics, environmental epigenomics, exploration of the use of surrogate tissues, and improved technologies for epigenome manipulation.

Nurses' role and care practices in decision-making regarding artificial ventilation in late stage pulmonary disease.

PubMed

Jerpseth, Heidi; Dahl, Vegard; Nortvedt, Per; Halvorsen, Kristin

2017-11-01

Decisions regarding whether or not to institute mechanical ventilation during the later stages of chronic obstructive pulmonary disease is challenging both ethically, emotionally and medically. Caring for these patients is a multifaceted process where nurses play a crucial role. Research question and design: We have investigated how nurses experienced their own role in decision-making processes regarding mechanical ventilation in later stages of chronic obstructive pulmonary disease and how they consider the patients' role in these processes. We applied a qualitative approach, with six focus-group interviews of nurses (n = 26). Ethical considerations: The Regional Committees for Medical and Health Research Ethics approved the study. Voluntary informed consent was obtained. The nurses found themselves operating within a cure-directed treatment culture wherein they were unable to stand up for the caring values. They perceived their roles and responsibilities in decision-making processes regarding mechanical ventilation to patients as unclear and unsatisfactory. They also experienced inadequate interdisciplinary cooperation. Lack of communication skills, the traditional hierarchical hospital culture together with operating in a medical-orientated treatment culture where caring values is rated as less important might explain the nurses' absence in participation in the decision about mechanical ventilation. To be able to advocate for the patients' and their own right to be included in decision-making processes, nurses need an awareness of their own responsibilities. This requires personal courage, leadership who are capable of organising common interpersonal meetings and willingness on the part of the physicians to include and value the nurses' participation in decision-making processes.

Using multitype branching processes to quantify statistics of disease outbreaks in zoonotic epidemics

NASA Astrophysics Data System (ADS)

Singh, Sarabjeet; Schneider, David J.; Myers, Christopher R.

2014-03-01

Branching processes have served as a model for chemical reactions, biological growth processes, and contagion (of disease, information, or fads). Through this connection, these seemingly different physical processes share some common universalities that can be elucidated by analyzing the underlying branching process. In this work we focus on coupled branching processes as a model of infectious diseases spreading from one population to another. An exceedingly important example of such coupled outbreaks are zoonotic infections that spill over from animal populations to humans. We derive several statistical quantities characterizing the first spillover event from animals to humans, including the probability of spillover, the first passage time distribution for human infection, and disease prevalence in the animal population at spillover. Large stochastic fluctuations in those quantities can make inference of the state of the system at the time of spillover difficult. Focusing on outbreaks in the human population, we then characterize the critical threshold for a large outbreak, the distribution of outbreak sizes, and associated scaling laws. These all show a strong dependence on the basic reproduction number in the animal population and indicate the existence of a novel multicritical point with altered scaling behavior. The coupling of animal and human infection dynamics has crucial implications, most importantly allowing for the possibility of large human outbreaks even when human-to-human transmission is subcritical.

Ecosystem processes related to wood decay

Treesearch

Bruce G. Marcot

2017-01-01

Wood decay elements include snags, down wood, root wads, tree stumps, litter, duff, broomed or diseased branches, and partially dead trees, all of which contribute to ecological processes and biodiversity of the forest ecosystem. Down wood can serve as reservoirs for moisture and mycorrhizal fungi beneficial to the health and growth of commercial tree species. Decaying...

Neurodegenerative Disease Transmission and Transgenesis in Mice.

PubMed

Dugger, Brittany N; Perl, Daniel P; Carlson, George A

2017-11-01

Although the discovery of the prion protein (PrP) resulted from its co-purification with scrapie infectivity in Syrian hamsters, work with genetically defined and genetically modified mice proved crucial for understanding the fundamental processes involved not only in prion diseases caused by PrP misfolding, aggregation, and spread but also in other, much more common, neurodegenerative brain diseases. In this review, we focus on methodological and conceptual approaches used to study scrapie and related PrP misfolding diseases in mice and how these approaches have advanced our understanding of related disorders including Alzheimer's and Parkinson's disease. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Molecular inflammation: underpinnings of aging and age-related diseases.

PubMed

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2009-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) upregulation of pro-inflammatory mediators (e.g., TNF-alpha, IL-1beta, IL-6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-kappaB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity.

Molecular Inflammation: Underpinnings of Aging and Age-related Diseases

PubMed Central

Chung, Hae Young; Cesari, Matteo; Anton, Stephen; Marzetti, Emanuele; Giovannini, Silvia; Seo, Arnold Young; Carter, Christy; Yu, Byung Pal; Leeuwenburgh, Christiaan

2013-01-01

Recent scientific studies have advanced the notion of chronic inflammation as a major risk factor underlying aging and age-related diseases. In this review, low-grade, unresolved, molecular inflammation is described as an underlying mechanism of aging and age-related diseases, which may serve as a bridge between normal aging and age-related pathological processes. Accumulated data strongly suggest that continuous (chronic) up-regulation of pro-inflammatory mediators (e.g., TNF-α, IL-1β, 6, COX-2, iNOS) are induced during the aging process due to an age-related redox imbalance that activates many pro-inflammatory signaling pathways, including the NF-κB signaling pathway. These pro-inflammatory molecular events are discussed in relation to their role as basic mechanisms underlying aging and age-related diseases. Further, the anti-inflammatory actions of aging-retarding caloric restriction and exercise are reviewed. Thus, the purpose of this review is to describe the molecular roles of age-related physiological functional declines and the accompanying chronic diseases associated with aging. This new view on the role of molecular inflammation as a mechanism of aging and age-related pathogenesis can provide insights into potential interventions that may affect the aging process and reduce age-related diseases, thereby promoting healthy longevity. PMID:18692159

The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer

PubMed Central

2011-01-01

The role of vitamin D (VitD) in calcium and bone homeostasis is well described. In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. VitD deficiency appears to be frequent in industrialized countries. Especially patients with lung diseases have often low VitD serum levels. Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases. Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer. The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells. This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status. PMID:21418564

Channel catfish

USDA-ARS?s Scientific Manuscript database

This book chapter provides a comprehensive overview of channel catfish aquaculture. Sections include fish biology; commercial culture; culture facilities; production practices; water quality management; nutrition, feeding and feed formulation; infectious diseases; harvesting and processing; and the...

The Facially Disfigured Child.

ERIC Educational Resources Information Center

Moncada, Georgia A.

1987-01-01

The article reviews diagnosis and treatments for facially disfigured children including craniofacial reconstruction and microsurgical techniques. Noted are associated disease processes that affect the social and intellectual outcomes of the afflicted child. (Author/DB)

System theory in medical diagnostic devices: an overview.

PubMed

Baura, Gail D

2006-01-01

Medical diagnostics refers to testing conducted either in vitro or in vivo to provide critical health care information for risk assessment, early diagnosis, treatment, or disease management. Typical in vivo diagnostic tests include the computed tomography scan, magnetic resonance imaging, and blood pressure screening. Typical in vitro diagnostic tests include cholesterol, Papanicolaou smear, and conventional glucose monitoring tests. Historically, devices associated with both types of diagnostics have used heuristic curve fitting during signal analysis. However, since the early 1990s, a few enterprising engineers and physicians have used system theory to improve their core processing for feature detection and system identification. Current applications include automated Pap smear screening for detection of cervical cancer and diagnosis of Alzheimer's disease. Future applications, such as disease prediction before symptom onset and drug treatment customization, have been catalyzed by the Human Genome Project.

Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications

PubMed Central

Hua, Yinan; Nair, Sreejayan

2014-01-01

Cardiovascular disease is the leading cause of death in the U.S. and other developed country. Metabolic syndrome, including obesity, diabetes/insulin resistance, hypertension and dyslipidemia is major threat for public health in the modern society. It is well established that metabolic syndrome contributes to the development of cardiovascular disease collective called as cardiometabolic disease. Despite documented studies in the research field of cardiometabolic disease, the underlying mechanisms are far from clear. Proteases are enzymes that break down proteins, many of which have been implicated in various diseases including cardiac disease. Matrix metalloproteinase (MMP), calpain, cathepsin and caspase are among the major proteases involved in cardiac remodeling. Recent studies have also implicated proteases in the pathogenesis of cardiometabolic disease. Elevated expression and activities of proteases in atherosclerosis, coronary heart disease, obesity/insulin-associated heart disease as well as hypertensive heart disease have been documented. Furthermore, transgenic animals that are deficient in or overexpress proteases allow scientists to understand the causal relationship between proteases and cardiometabolic disease. Mechanistically, MMPs and cathepsins exert their effect on cardiometabolic diseases mainly through modifying the extracellular matrix. However, MMP and cathepsin are also reported to affect intracellular proteins, by which they contribute to the development of cardiometabolic diseases. On the other hand, activation of calpain and caspases has been shown to influence intracellular signaling cascade including the NF-κB and apoptosis pathways. Clinically, proteases are reported to function as biomarkers of cardiometabolic diseases. More importantly, the inhibitors of proteases are credited with beneficial cardiometabolic profile, although the exact molecular mechanisms underlying these salutary effects are still under investigation. A better understanding of the role of MMPs, cathepsins, calpains and caspases in cardiometabolic diseases process may yield novel therapeutic targets for threating or controlling these diseases. PMID:24815358

Mathematical Modeling of Protein Misfolding Mechanisms in Neurological Diseases: A Historical Overview.

PubMed

Carbonell, Felix; Iturria-Medina, Yasser; Evans, Alan C

2018-01-01

Protein misfolding refers to a process where proteins become structurally abnormal and lose their specific 3-dimensional spatial configuration. The histopathological presence of misfolded protein (MP) aggregates has been associated as the primary evidence of multiple neurological diseases, including Prion diseases, Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob disease. However, the exact mechanisms of MP aggregation and propagation, as well as their impact in the long-term patient's clinical condition are still not well understood. With this aim, a variety of mathematical models has been proposed for a better insight into the kinetic rate laws that govern the microscopic processes of protein aggregation. Complementary, another class of large-scale models rely on modern molecular imaging techniques for describing the phenomenological effects of MP propagation over the whole brain. Unfortunately, those neuroimaging-based studies do not take full advantage of the tremendous capabilities offered by the chemical kinetics modeling approach. Actually, it has been barely acknowledged that the vast majority of large-scale models have foundations on previous mathematical approaches that describe the chemical kinetics of protein replication and propagation. The purpose of the current manuscript is to present a historical review about the development of mathematical models for describing both microscopic processes that occur during the MP aggregation and large-scale events that characterize the progression of neurodegenerative MP-mediated diseases.

Diverse structures, functions and uses of FK506 binding proteins.

PubMed

Bonner, Julia Maeve; Boulianne, Gabrielle L

2017-10-01

FK506 (Tacrolimus), isolated from Streptomyces tsukubaenis is a powerful immunosuppressant shown to inhibit T cell activation. FK506 mediated immunosuppression requires the formation of a complex between FK506, a FK506 binding protein (FKBP) and calcineurin. Numerous FKBPs have been identified in a wide range of species, from single celled organisms to humans. FKBPs show peptidylprolyl cis/trans isomerase (PPIase) activity and have been shown to affect a wide range of cellular processes including protein folding, receptor signaling and apoptosis. FKBPs also affect numerous biological functions in addition to immunosuppression including regulation of cardiac function, neuronal function and development and have been implicated in several diseases including cardiac disease, cancer and neurodegenerative diseases such as Alzheimer's disease. More recently, FKBPs have proven useful as molecular tools for studying protein interactions, localization and functions. This review provides an overview of the current state of knowledge of FKBPs and their numerous biological functions and uses. Copyright © 2017 Elsevier Inc. All rights reserved.

Method and system for the diagnosis of disease using retinal image content and an archive of diagnosed human patient data

DOEpatents

Tobin, Kenneth W; Karnowski, Thomas P; Chaum, Edward

2013-08-06

A method for diagnosing diseases having retinal manifestations including retinal pathologies includes the steps of providing a CBIR system including an archive of stored digital retinal photography images and diagnosed patient data corresponding to the retinal photography images, the stored images each indexed in a CBIR database using a plurality of feature vectors, the feature vectors corresponding to distinct descriptive characteristics of the stored images. A query image of the retina of a patient is obtained. Using image processing, regions or structures in the query image are identified. The regions or structures are then described using the plurality of feature vectors. At least one relevant stored image from the archive based on similarity to the regions or structures is retrieved, and an eye disease or a disease having retinal manifestations in the patient is diagnosed based on the diagnosed patient data associated with the relevant stored image(s).

Principles and approaches to the treatment of immune-mediated movement disorders.

PubMed

Mohammad, Shekeeb S; Dale, Russell C

2018-03-01

Immune mediated movement disorders include movement disorders in the context of autoimmune encephalitis such as anti-NMDAR encephalitis, post-infectious autoimmune movement disorders such as Sydenham chorea, paraneoplastic autoimmune movement disorders such as opsoclonus myoclonus ataxia syndrome, and infection triggered conditions such as paediatric acute neuropsychiatric syndrome. This review focuses on the approach to treatment of immune mediated movement disorders, which requires an understanding of the immunopathogenesis, whether the disease is destructive or 'altering', and the natural history of disease. Factors that can influence outcome include the severity of disease, the delay before starting therapy, use of multimodal therapy and whether the course is monophasic or relapsing. Although the four main conditions listed above have different pathophysiological processes, there are general themes that broadly apply including: early diagnosis and treatment is better, minimise the severity of disease, escalate treatment if the patient is not responding to initial treatments, and minimise relapse. Copyright © 2017. Published by Elsevier Ltd.

Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera)

PubMed Central

2012-01-01

Background Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor. The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. Results We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor. We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Conclusions Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation. PMID:23021491

Correlation of proteome-wide changes with social immunity behaviors provides insight into resistance to the parasitic mite, Varroa destructor, in the honey bee (Apis mellifera).

PubMed

Parker, Robert; Guarna, M Marta; Melathopoulos, Andony P; Moon, Kyung-Mee; White, Rick; Huxter, Elizabeth; Pernal, Stephen F; Foster, Leonard J

2012-06-29

Disease is a major factor driving the evolution of many organisms. In honey bees, selection for social behavioral responses is the primary adaptive process facilitating disease resistance. One such process, hygienic behavior, enables bees to resist multiple diseases, including the damaging parasitic mite Varroa destructor. The genetic elements and biochemical factors that drive the expression of these adaptations are currently unknown. Proteomics provides a tool to identify proteins that control behavioral processes, and these proteins can be used as biomarkers to aid identification of disease tolerant colonies. We sampled a large cohort of commercial queen lineages, recording overall mite infestation, hygiene, and the specific hygienic response to V. destructor. We performed proteome-wide correlation analyses in larval integument and adult antennae, identifying several proteins highly predictive of behavior and reduced hive infestation. In the larva, response to wounding was identified as a key adaptive process leading to reduced infestation, and chitin biosynthesis and immune responses appear to represent important disease resistant adaptations. The speed of hygienic behavior may be underpinned by changes in the antenna proteome, and chemosensory and neurological processes could also provide specificity for detection of V. destructor in antennae. Our results provide, for the first time, some insight into how complex behavioural adaptations manifest in the proteome of honey bees. The most important biochemical correlations provide clues as to the underlying molecular mechanisms of social and innate immunity of honey bees. Such changes are indicative of potential divergence in processes controlling the hive-worker maturation.

Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging.

PubMed

Grammatikakis, Ioannis; Panda, Amaresh C; Abdelmohsen, Kotb; Gorospe, Myriam

2014-12-01

During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits.

Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging

PubMed Central

Abdelmohsen, Kotb; Gorospe, Myriam

2014-01-01

During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits. PMID:25543668

A framework for physician assistant intervention for overweight and obesity.

PubMed

Herman, Lawrence; McGinnity, John G; Doll, Michael; Peterson, Eric D; Russell, Amanda; Largay, Joseph

2015-07-01

Overweight and obesity compose a chronic disease process of epidemic proportions that presents on a continuum, likely affecting nearly two out of every three patients treated by physician assistants (PAs). However, meaningful and actionable definitions, including but not limited to anthropometric and clinical descriptors, are needed. The effective treatment of overweight and obesity requires an efficient and timely process of screening, diagnosis, evaluation of complications, staging, and clear algorithmic management. PAs are trained as primary care providers and can diagnose and treat overweight and obese patients regardless of practice setting and across the spectrum of the disease and patient's age.

A Chronic Disease Prevention and Management Corridor© to Supporting System-Level Transformations for Chronic Conditions.

PubMed

Sampalli, Tara; Christian, Erin; Edwards, Lynn; Ryer, Ashley

2015-01-01

Improving care for chronic conditions requires system-level transformations to ensure multiple levels of adoption and sustainability of the implemented improvements. These comprehensive solutions require transformations and supports at various levels, leadership and process changes at service/program level. Recognizing the importance of an organization-wide strategy to mitigate the growing issue of chronic disease prevention and management, a novel system-level approach has been developed in a district health authority in Nova Scotia, Canada. In this paper, the contextual factors and efforts that led to the conceptual framework of the Chronic Disease Prevention and Management (CDPM) "Corridor©" to management of chronic conditions are discussed. The CDPM Corridor© essentially constitutes a system-level redesign process; common elements, tools and resources; and a hub of supports for chronic disease prevention and management. The CDPM Corridor © will include a toolkit to guide the implementation of the proposed transformations.

Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

PubMed

Arnett, S V; Clark, I A

2012-12-10

Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management. Copyright © 2012 Elsevier B.V. All rights reserved.

The potential of disease management for neuromuscular hereditary disorders.

PubMed

Chouinard, Maud-Christine; Gagnon, Cynthia; Laberge, Luc; Tremblay, Carmen; Côté, Charlotte; Leclerc, Nadine; Mathieu, Jean

2009-01-01

Neuromuscular hereditary disorders require long-term multidisciplinary rehabilitation management. Although the need for coordinated healthcare management has long been recognized, most neuromuscular disorders are still lacking clinical guidelines about their long-term management and structured evaluation plan with associated services. One of the most prevalent adult-onset neuromuscular disorders, myotonic dystrophy type 1, generally presents several comorbidities and a variable clinical picture, making management a constant challenge. This article presents a healthcare follow-up plan and proposes a nursing case management within a disease management program as an innovative and promising approach. This disease management program and model consists of eight components including population identification processes, evidence-based practice guidelines, collaborative practice, patient self-management education, and process outcomes evaluation (Disease Management Association of America, 2004). It is believed to have the potential to significantly improve healthcare management for neuromuscular hereditary disorders and will prove useful to nurses delivering and organizing services for this population.

Multidisciplinary approach to R&D in vitiligo, a neglected skin disease.

PubMed

Valle, Yan; Lotti, Torello M; Hercogova, Jana; Schwartz, Robert A; Korobko, Igor V

2012-01-01

A global interest in therapies for neglected diseases is rising, but traditional biopharma research and development (R&D) process is prohibitively expensive to justify cost of their development. Vitiligo is a multifactorial orphan disease that affects at minimum 35 million people worldwide, yet no therapeutic solutions exist. The present authors describe a budget-minded pursuit of the new therapy development for vitiligo, which includes a multidiscipline collaboration and effective bridging between academic research, biobanking, and bioinformatics. The present authors anticipate that the present authors' "theoretically induced and empirically guided" discovery process will enable development of more leads, with a much greater probability of success and under tighter budgets compared with those of the biopharma company. Ultimately, the multidisciplinary approach described below facilitates the collaborative development of personalized treatments for different patient subpopulations in vitiligo and other neglected diseases. © 2012 Wiley Periodicals, Inc.

Inter relationship of Ayurveda and Astrology

PubMed Central

Dwivedi, Jaiprakash Narayan

2013-01-01

In the universe all the creatures are related to Adhivyadhi, which indicates mental agony or bodily pain. Acharyas of Ayurveda like Charaka, Sushruta and Kashyap have classified diseases into various categories like Agantuja, Sharirika, Manasika, Swabhavika, etc. Charaka classified diseases based on the prognosis like Sadhya, Asadhya, Mrudu and Daruna. Ayurveda also suggested Daiva Vyapashraya Chikitsa which includes of Manidharana and chanting Mantras. Astrological sciences suggest 10 types of remedial measures in the treatment of diseases. This science considers that causative factors of various disorders are the Navagrahas (nine planets). The influence of the planets on various procedures like drug processing, bath taking, performing Yajna, wearing Ratna, etc. are well documented in Jyotishashastra. Drugs processed in Chandra Nakshatra acts as ambrosia and subdues Tridoshajanya Vyadhi. Medicated baths are suggested for diseases engendered due to involvement of different planet effects viz. Sarshpa for Shukra, Haridra and Daruharidra for Shani Lodhra for Ketu, Sharpunkha for Rahu, etc. In a close scrutiny it appears that Jyotishashastra Siddhanta can play crucial role in the management of chronic diseases. PMID:24049402

Inter relationship of Ayurveda and Astrology.

PubMed

Dwivedi, Jaiprakash Narayan

2013-01-01

In the universe all the creatures are related to Adhivyadhi, which indicates mental agony or bodily pain. Acharyas of Ayurveda like Charaka, Sushruta and Kashyap have classified diseases into various categories like Agantuja, Sharirika, Manasika, Swabhavika, etc. Charaka classified diseases based on the prognosis like Sadhya, Asadhya, Mrudu and Daruna. Ayurveda also suggested Daiva Vyapashraya Chikitsa which includes of Manidharana and chanting Mantras. Astrological sciences suggest 10 types of remedial measures in the treatment of diseases. This science considers that causative factors of various disorders are the Navagrahas (nine planets). The influence of the planets on various procedures like drug processing, bath taking, performing Yajna, wearing Ratna, etc. are well documented in Jyotishashastra. Drugs processed in Chandra Nakshatra acts as ambrosia and subdues Tridoshajanya Vyadhi. Medicated baths are suggested for diseases engendered due to involvement of different planet effects viz. Sarshpa for Shukra, Haridra and Daruharidra for Shani Lodhra for Ketu, Sharpunkha for Rahu, etc. In a close scrutiny it appears that Jyotishashastra Siddhanta can play crucial role in the management of chronic diseases.

CT Angiography after 20 Years

PubMed Central

Rubin, Geoffrey D.; Leipsic, Jonathon; Schoepf, U. Joseph; Fleischmann, Dominik; Napel, Sandy

2015-01-01

Through a marriage of spiral computed tomography (CT) and graphical volumetric image processing, CT angiography was born 20 years ago. Fueled by a series of technical innovations in CT and image processing, over the next 5–15 years, CT angiography toppled conventional angiography, the undisputed diagnostic reference standard for vascular disease for the prior 70 years, as the preferred modality for the diagnosis and characterization of most cardiovascular abnormalities. This review recounts the evolution of CT angiography from its development and early challenges to a maturing modality that has provided unique insights into cardiovascular disease characterization and management. Selected clinical challenges, which include acute aortic syndromes, peripheral vascular disease, aortic stent-graft and transcatheter aortic valve assessment, and coronary artery disease, are presented as contrasting examples of how CT angiography is changing our approach to cardiovascular disease diagnosis and management. Finally, the recently introduced capabilities for multispectral imaging, tissue perfusion imaging, and radiation dose reduction through iterative reconstruction are explored with consideration toward the continued refinement and advancement of CT angiography. PMID:24848958

Autoinflammatory bone diseases.

PubMed

Stern, Sara M; Ferguson, Polly J

2013-11-01

Autoinflammatory bone disease is a new branch of autoinflammatory diseases caused by seemingly unprovoked activation of the innate immune system leading to an osseous inflammatory process. The inflammatory bone lesions in these disorders are characterized by chronic inflammation that is typically culture negative with no demonstrable organism on histopathology. The most common autoinflammatory bone diseases in childhood include chronic nonbacterial osteomyelitis (CNO), synovitis, acne, pustulosis, hyperostosis, osteitis syndrome, Majeed syndrome, deficiency of interleukin-1 receptor antagonist, and cherubism. In this article, the authors focus on CNO and summarize the distinct genetic autoinflammatory bone syndromes. Copyright © 2013 Elsevier Inc. All rights reserved.

SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease

PubMed Central

Li, Darrick K.; Tisdale, Sarah; Lotti, Francesco; Pellizzoni, Livio

2014-01-01

At the post-transcriptional level, expression of protein-coding genes is controlled by a series of RNA regulatory events including nuclear processing of primary transcripts, transport of mature mRNAs to specific cellular compartments, translation and ultimately, turnover. These processes are orchestrated through the dynamic association of mRNAs with RNA binding proteins and ribonucleoprotein (RNP) complexes. Accurate formation of RNPs in vivo is fundamentally important to cellular development and function, and its impairment often leads to human disease. The survival motor neuron (SMN) protein is key to this biological paradigm: SMN is essential for the biogenesis of various RNPs that function in mRNA processing, and genetic mutations leading to SMN deficiency cause the neurodegenerative disease spinal muscular atrophy. Here we review the expanding role of SMN in the regulation of gene expression through its multiple functions in RNP assembly. We discuss advances in our understanding of SMN activity as a chaperone of RNPs and how disruption of SMN-dependent RNA pathways can cause motor neuron disease. PMID:24769255

Assessing technical performance at diverse ambulatory care sites.

PubMed

Osterweis, M; Bryant, E

1978-01-01

The purpose of the large study reported here was to develop and test methods for assessing the quality of health care that would be broadly applicable to diverse ambulatory care organizations for periodic comparative review. Methodological features included the use of an age-sex stratified random sampling scheme, dependence on medical records as the source of data, a fixed study period year, use of Kessner's tracer methodology (including not only acute and chronic diseases but also screening and immunization rates as indicators), and a fixed tracer matrix at all test sites. This combination of methods proved more efficacious in estimating certain parameters for the total patient populations at each site (including utilization patterns, screening, and immunization rates) and the process of care for acute conditions than it did in examining the process of care for the selected chronic condition. It was found that the actual process of care at all three sites for the three acute conditions (streptococcal pharyngitis, urinary tract infection, and iron deficiency anemia) often differed from the expected process in terms of both diagnostic procedures and treatment. For hypertension, the chronic disease tracer, medical records were frequently a deficient data source from which to draw conclusions about the adequacy of treatment. Several aspects of the study methodology were found to be detrimental to between-site comparisons of the process of care for chronic disease management. The use of an age-sex stratified random sampling scheme resulted in the identification of too few cases of hypertension at some sites for analytic purposes, thereby necessitating supplementary sampling by diagnosis. The use of a fixed study period year resulted in an arbitrary starting point in the course of the disease. Furthermore, in light of the diverse sociodemographic characteristics of the patient populations, the use of a fixed matrix of tracer conditions for all test sites is questionable. The discussion centers on these and other problems encountered in attempting to compare technical performance within diverse ambulatory care organizations and provides some guidelines as to the utility of alternative methods for assessing the quality of health care.

Statistical Process Control: A Quality Tool for a Venous Thromboembolic Disease Registry.

PubMed

Posadas-Martinez, Maria Lourdes; Rojas, Liliana Paloma; Vazquez, Fernando Javier; De Quiros, Fernan Bernaldo; Waisman, Gabriel Dario; Giunta, Diego Hernan

2016-01-01

We aim to describe Statistical Control Process as a quality tool for the Institutional Registry of Venous Thromboembolic Disease (IRTD), a registry developed in a community-care tertiary hospital in Buenos Aires, Argentina. The IRTD is a prospective cohort. The process of data acquisition began with the creation of a computerized alert generated whenever physicians requested imaging or laboratory study to diagnose venous thromboembolism, which defined eligible patients. The process then followed a structured methodology for patient's inclusion, evaluation, and posterior data entry. To control this process, process performance indicators were designed to be measured monthly. These included the number of eligible patients, the number of included patients, median time to patient's evaluation, and percentage of patients lost to evaluation. Control charts were graphed for each indicator. The registry was evaluated in 93 months, where 25,757 patients were reported and 6,798 patients met inclusion criteria. The median time to evaluation was 20 hours (SD, 12) and 7.7% of the total was lost to evaluation. Each indicator presented trends over time, caused by structural changes and improvement cycles, and therefore the central limit suffered inflexions. Statistical process control through process performance indicators allowed us to control the performance of the registry over time to detect systematic problems. We postulate that this approach could be reproduced for other clinical registries.

In vivo and in vitro IL-18 production during uveitis associated with Behçet disease: effect of glucocorticoid therapy.

PubMed

Belguendouz, H; Messaoudene, D; Lahmar-Belguendouz, K; Djeraba, Z; Otmani, F; Terahi, M; Tiar, M; Hartani, D; Lahlou-Boukoffa, O S; Touil-Boukoffa, C

2015-03-01

Uveitis represents one of the major diagnostic criteria in Behçet's disease. It is most prevalent in the countries of the Mediterranean area, including Algeria, and along the Silk Road. Clinical features include oral and genital ulcers, ocular and skin lesions, as well as central nervous system, joint, vascular, gastrointestinal, or pulmonary manifestations. Many studies have reported that Th1 immune responses are involved in the physiopathology. We have previously studied the production of IL-12 and IFN-γ, cytokine markers in the Th1 pathway involved in Behçet's disease. In our study, we investigate in vivo and in vitro IL-18 production in Algerian patients with Behçet's disease with ocular manifestations in various stages of the disease. We examined the effect of glucocorticoids on IL-18 production during the active stage of the disease. Our results suggest that IL-18 could be a good biomarker for monitoring disease activity and its regression, demonstrating the effectiveness of treatment on the underlying immunopathologic process. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

SU-E-CAMPUS-J-04: Image Guided Radiation Therapy (IGRT): Review of Technical Standards and Credentialing in Radiotherapy Clinical Trials

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

Giaddui, T; Chen, W; Yu, J

2014-06-15

Purpose: To review IGRT credentialing experience and unexpected technical issues encountered in connection with advanced radiotherapy technologies as implemented in RTOG clinical trials. To update IGRT credentialing procedures with the aim of improving the quality of the process, and to increase the proportion of IGRT credentialing compliance. To develop a living disease site-specific IGRT encyclopedia. Methods: Numerous technical issues were encountered during the IGRT credentialing process. The criteria used for credentialing review were based on: image quality; anatomy included in fused data sets and shift results. Credentialing requirements have been updated according to the AAPM task group reports for IGRTmore » to ensure that all required technical items are included in the quality review process. Implementation instructions have been updated and expanded for recent protocols. Results: Technical issues observed during the credentialing review process include, but are not limited to: poor quality images; inadequate image acquisition region; poor data quality; shifts larger than acceptable; no soft tissue surrogate. The updated IGRT credentialing process will address these issues and will also include the technical items required from AAPM: TG 104; TG 142 and TG 179 reports. An instruction manual has been developed describing a remote credentialing method for reviewers. Submission requirements are updated, including images/documents as well as facility questionnaire. The review report now includes summary of the review process and the parameters that reviewers check. We have reached consensus on the minimum IGRT technical requirement for a number of disease sites. RTOG 1311(NRG-BR002A Phase 1 Study of Stereotactic Body Radiotherapy (SBRT) for the Treatment of Multiple Metastases) is an example, here; the protocol specified the minimum requirement for each anatomical sites (with/without fiducials). Conclusion: Technical issues are identified and reported. IGRT guidelines are updated, with the corresponding credentialing requirements. An IGRT encyclopedia describing site-specific implementation issues is currently in development.« less

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

Monitoring-Based Model for Personalizing the Clinical Process of Crohn’s Disease

PubMed Central

de Ramón-Fernández, Alberto; Ruiz-Fernández, Daniel; Vives-Boix, Víctor

2017-01-01

Crohn’s disease is a chronic pathology belonging to the group of inflammatory bowel diseases. Patients suffering from Crohn’s disease must be supervised by a medical specialist for the rest of their lives; furthermore, each patient has its own characteristics and is affected by the disease in a different way, so health recommendations and treatments cannot be generalized and should be individualized for a specific patient. To achieve this personalization in a cost-effective way using technology, we propose a model based on different information flows: control, personalization, and monitoring. As a result of the model and to perform a functional validation, an architecture based on services and a prototype of the system has been defined. In this prototype, a set of different devices and technologies to monitor variables from patients and their environment has been integrated. Artificial intelligence algorithms are also included to reduce the workload related to the review and analysis of the information gathered. Due to the continuous and automated monitoring of the Crohn’s patient, this proposal can help in the personalization of the Crohn’s disease clinical process. PMID:28678162

A radiographic anthology of vertebral names.

PubMed

Yochum, T R; Hartley, B; Thomas, D P; Guebert, G M

1985-06-01

There are many conditions of the spine to which various authors have applied descriptive names. This paper, an extensive review of the literature, provides the first complete source for such named vertebrae. Included are 88 names covering all categories of bone disease. A brief description of the radiographic appearance and its pathogenesis is provided for each, along with a consideration of the disease processes which may produce the appearance.

Applying data mining techniques to determine important parameters in chronic kidney disease and the relations of these parameters to each other.

PubMed

Tahmasebian, Shahram; Ghazisaeedi, Marjan; Langarizadeh, Mostafa; Mokhtaran, Mehrshad; Mahdavi-Mazdeh, Mitra; Javadian, Parisa

2017-01-01

Introduction: Chronic kidney disease (CKD) includes a wide range of pathophysiological processes which will be observed along with abnormal function of kidneys and progressive decrease in glomerular filtration rate (GFR). According to the definition decreasing GFR must have been present for at least three months. CKD will eventually result in end-stage kidney disease. In this process different factors play role and finding the relations between effective parameters in this regard can help to prevent or slow progression of this disease. There are always a lot of data being collected from the patients' medical records. This huge array of data can be considered a valuable source for analyzing, exploring and discovering information. Objectives: Using the data mining techniques, the present study tries to specify the effective parameters and also aims to determine their relations with each other in Iranian patients with CKD. Material and Methods: The study population includes 31996 patients with CKD. First, all of the data is registered in the database. Then data mining tools were used to find the hidden rules and relationships between parameters in collected data. Results: After data cleaning based on CRISP-DM (Cross Industry Standard Process for Data Mining) methodology and running mining algorithms on the data in the database the relationships between the effective parameters was specified. Conclusion: This study was done using the data mining method pertaining to the effective factors on patients with CKD.

Applying data mining techniques to determine important parameters in chronic kidney disease and the relations of these parameters to each other

PubMed Central

Tahmasebian, Shahram; Ghazisaeedi, Marjan; Langarizadeh, Mostafa; Mokhtaran, Mehrshad; Mahdavi-Mazdeh, Mitra; Javadian, Parisa

2017-01-01

Introduction: Chronic kidney disease (CKD) includes a wide range of pathophysiological processes which will be observed along with abnormal function of kidneys and progressive decrease in glomerular filtration rate (GFR). According to the definition decreasing GFR must have been present for at least three months. CKD will eventually result in end-stage kidney disease. In this process different factors play role and finding the relations between effective parameters in this regard can help to prevent or slow progression of this disease. There are always a lot of data being collected from the patients’ medical records. This huge array of data can be considered a valuable source for analyzing, exploring and discovering information. Objectives: Using the data mining techniques, the present study tries to specify the effective parameters and also aims to determine their relations with each other in Iranian patients with CKD. Material and Methods: The study population includes 31996 patients with CKD. First, all of the data is registered in the database. Then data mining tools were used to find the hidden rules and relationships between parameters in collected data. Results: After data cleaning based on CRISP-DM (Cross Industry Standard Process for Data Mining) methodology and running mining algorithms on the data in the database the relationships between the effective parameters was specified. Conclusion: This study was done using the data mining method pertaining to the effective factors on patients with CKD. PMID:28497080

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

PubMed

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

2018-04-11

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

Gene-Disease Network Analysis Reveals Functional Modules in Mendelian, Complex and Environmental Diseases

PubMed Central

Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A.; Sanz, Ferran; Furlong, Laura I.

2011-01-01

Background Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. Principal Findings We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. Conclusions For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. Availability The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download. PMID:21695124

Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases.

PubMed

Bauer-Mehren, Anna; Bundschus, Markus; Rautschka, Michael; Mayer, Miguel A; Sanz, Ferran; Furlong, Laura I

2011-01-01

Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download.

SymptomCare@Home: Developing an Integrated Symptom Monitoring and Management System for Outpatients Receiving Chemotherapy.

PubMed

Beck, Susan L; Eaton, Linda H; Echeverria, Christina; Mooney, Kathi H

2017-10-01

SymptomCare@Home, an integrated symptom monitoring and management system, was designed as part of randomized clinical trials to help patients with cancer who receive chemotherapy in ambulatory clinics and often experience significant symptoms at home. An iterative design process was informed by chronic disease management theory and features of assessment and clinical decision support systems used in other diseases. Key stakeholders participated in the design process: nurse scientists, clinical experts, bioinformatics experts, and computer programmers. Especially important was input from end users, patients, and nurse practitioners participating in a series of studies testing the system. The system includes both a patient and clinician interface and fully integrates two electronic subsystems: a telephone computer-linked interactive voice response system and a Web-based Decision Support-Symptom Management System. Key features include (1) daily symptom monitoring, (2) self-management coaching, (3) alerting, and (4) nurse practitioner follow-up. The nurse practitioner is distinctively positioned to provide assessment, education, support, and pharmacologic and nonpharmacologic interventions to intensify management of poorly controlled symptoms at home. SymptomCare@Home is a model for providing telehealth. The system facilitates using evidence-based guidelines as part of a comprehensive symptom management approach. The design process and system features can be applied to other diseases and conditions.

Epidemiological Trends Strongly Suggest Exposures as Etiologic Agents in the Pathogenesis of Sporadic Alzheimer's Disease, Diabetes Mellitus, and Non-Alcoholic Steatohepatitis

PubMed Central

de la Monte, Suzanne M.; Neusner, Alexander; Chu, Jennifer; Lawton, Margot

2015-01-01

Nitrosamines mediate their mutagenic effects by causing DNA damage, oxidative stress, lipid peroxidation, and pro-inflammatory cytokine activation, which lead to increased cellular degeneration and death. However, the very same pathophysiological processes comprise the “unbuilding” blocks of aging and insulin-resistance diseases including, neurodegeneration, diabetes mellitus (DM), and non-alcoholic steatohepatitis (NASH). Previous studies demonstrated that experimental exposure to streptozotocin, a nitrosamine-related compound, causes NASH, and diabetes mellitus Types 1, 2 and 3 (Alzheimer (AD)-type neurodegeneration). Herein, we review evidence that the upwardly spiraling trends in mortality rates due to DM, AD, and Parkinson's disease typify exposure rather than genetic-based disease models, and parallel the progressive increases in human exposure to nitrates, nitrites, and nitrosamines via processed/preserved foods. We propose that such chronic exposures have critical roles in the pathogenesis of our insulin resistance disease pandemic. Potential solutions include: 1) eliminating the use of nitrites in food; 2) reducing nitrate levels in fertilizer and water used to irrigate crops; and 3) employing safe and effective measures to detoxify food and water prior to human consumption. Future research efforts should focus on refining our ability to detect and monitor human exposures to nitrosamines and assess early evidence of nitrosamine-mediated tissue injury and insulin resistance. PMID:19363256

A systematic review of validated methods for identifying pulmonary fibrosis and interstitial lung disease using administrative and claims data.

PubMed

Jones, Natalie; Schneider, Gary; Kachroo, Sumesh; Rotella, Philip; Avetisyan, Ruzan; Reynolds, Matthew W

2012-01-01

The Food and Drug Administration's Mini-Sentinel pilot program initially aimed to conduct active surveillance to refine safety signals that emerge for marketed medical products. A key facet of this surveillance is to develop and understand the validity of algorithms for identifying health outcomes of interest (HOIs) from administrative and claims data. This paper summarizes the process and findings of the algorithm review of pulmonary fibrosis and interstitial lung disease. PubMed and Iowa Drug Information Service Web searches were conducted to identify citations applicable to the pulmonary fibrosis/interstitial lung disease HOI. Level 1 abstract reviews and Level 2 full-text reviews were conducted to find articles using administrative and claims data to identify pulmonary fibrosis and interstitial lung disease, including validation estimates of the coding algorithms. Our search revealed a deficiency of literature focusing on pulmonary fibrosis and interstitial lung disease algorithms and validation estimates. Only five studies provided codes; none provided validation estimates. Because interstitial lung disease includes a broad spectrum of diseases, including pulmonary fibrosis, the scope of these studies varied, as did the corresponding diagnostic codes used. Research needs to be conducted on designing validation studies to test pulmonary fibrosis and interstitial lung disease algorithms and estimating their predictive power, sensitivity, and specificity. Copyright © 2012 John Wiley & Sons, Ltd.

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research.

PubMed

McCann, Liza J; Pilkington, Clarissa A; Huber, Adam M; Ravelli, Angelo; Appelbe, Duncan; Kirkham, Jamie J; Williamson, Paula R; Aggarwal, Amita; Christopher-Stine, Lisa; Constantin, Tamas; Feldman, Brian M; Lundberg, Ingrid; Maillard, Sue; Mathiesen, Pernille; Murphy, Ruth; Pachman, Lauren M; Reed, Ann M; Rider, Lisa G; van Royen-Kerkof, Annet; Russo, Ricardo; Spinty, Stefan; Wedderburn, Lucy R; Beresford, Michael W

2018-02-01

This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres. A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation. A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter. Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Human neutrophils in auto-immunity.

PubMed

Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

2016-04-01

Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Proposal for an integrated evaluation model for the study of whole systems health care in cancer.

PubMed

Jonas, Wayne B; Beckner, William; Coulter, Ian

2006-12-01

For more than 200 years, biomedicine has approached the treatment of disease by studying disease processes (patho-genesis), inferring causal connections and developing specific approaches for therapeutically interfering with those processes. This pathogenic approach has been highly successful in acute and traumatic disease but less successful in chronic disease, primarily because of the complex, multi-factorial nature of most chronic disease, which does not allow for simple causal inference or for simple therapeutic interventions. This article suggests that chronic disease is best approached by enhancing healing processes (salutogenesis) as a whole system. Because of the nature of complex systems in chronic disease, an evaluation model based on integrative medicine is felt to be more appropriate than a disease model. The authors propose and describe an integrated model for the evaluation of healing (IMEH) that collects multilevel "thick case" observational data in assessing complex practices for chronic disease. If successful, this approach could become a blueprint for studying healing capacity in whole medical systems, including complementary medicine, traditional medicine, and conventional primary care. In addition, streamlining data collection and applying rapid informatics management might allow for such data to be used in guiding clinical practice. The IMEH involves collection, integration, and potentially feedback of relevant variables in the following areas: (1) sociocultural, (2) psychological and behavioral, (3) clinical (diagnosis based), and (4) biological. Evaluation and integration of these components would involve specialized research teams that feed their data into a single data management and information analysis center. These data can then be subjected to descriptive and pathway analysis providing "bench and bedside" information.

Application of a theoretical model to evaluate COPD disease management.

PubMed

Lemmens, Karin M M; Nieboer, Anna P; Rutten-Van Mölken, Maureen P M H; van Schayck, Constant P; Asin, Javier D; Dirven, Jos A M; Huijsman, Robbert

2010-03-26

Disease management programmes are heterogeneous in nature and often lack a theoretical basis. An evaluation model has been developed in which theoretically driven inquiries link disease management interventions to outcomes. The aim of this study is to methodically evaluate the impact of a disease management programme for patients with chronic obstructive pulmonary disease (COPD) on process, intermediate and final outcomes of care in a general practice setting. A quasi-experimental research was performed with 12-months follow-up of 189 COPD patients in primary care in the Netherlands. The programme included patient education, protocolised assessment and treatment of COPD, structural follow-up and coordination by practice nurses at 3, 6 and 12 months. Data on intermediate outcomes (knowledge, psychosocial mediators, self-efficacy and behaviour) and final outcomes (dyspnoea, quality of life, measured by the CRQ and CCQ, and patient experiences) were obtained from questionnaires and electronic registries. Implementation of the programme was associated with significant improvements in dyspnoea (p < 0.001) and patient experiences (p < 0.001). No significant improvement was found in mean quality of life scores. Improvements were found in several intermediate outcomes, including investment beliefs (p < 0.05), disease-specific knowledge (p < 0.01; p < 0.001) and medication compliance (p < 0.01). Overall, process improvement was established. The model showed associations between significantly improved intermediate outcomes and improvements in quality of life and dyspnoea. The application of a theory-driven model enhances the design and evaluation of disease management programmes aimed at improving health outcomes. This study supports the notion that a theoretical approach strengthens the evaluation designs of complex interventions. Moreover, it provides prudent evidence that the implementation of COPD disease management programmes can positively influence outcomes of care.

Application of a theoretical model to evaluate COPD disease management

PubMed Central

2010-01-01

Background Disease management programmes are heterogeneous in nature and often lack a theoretical basis. An evaluation model has been developed in which theoretically driven inquiries link disease management interventions to outcomes. The aim of this study is to methodically evaluate the impact of a disease management programme for patients with chronic obstructive pulmonary disease (COPD) on process, intermediate and final outcomes of care in a general practice setting. Methods A quasi-experimental research was performed with 12-months follow-up of 189 COPD patients in primary care in the Netherlands. The programme included patient education, protocolised assessment and treatment of COPD, structural follow-up and coordination by practice nurses at 3, 6 and 12 months. Data on intermediate outcomes (knowledge, psychosocial mediators, self-efficacy and behaviour) and final outcomes (dyspnoea, quality of life, measured by the CRQ and CCQ, and patient experiences) were obtained from questionnaires and electronic registries. Results Implementation of the programme was associated with significant improvements in dyspnoea (p < 0.001) and patient experiences (p < 0.001). No significant improvement was found in mean quality of life scores. Improvements were found in several intermediate outcomes, including investment beliefs (p < 0.05), disease-specific knowledge (p < 0.01; p < 0.001) and medication compliance (p < 0.01). Overall, process improvement was established. The model showed associations between significantly improved intermediate outcomes and improvements in quality of life and dyspnoea. Conclusions The application of a theory-driven model enhances the design and evaluation of disease management programmes aimed at improving health outcomes. This study supports the notion that a theoretical approach strengthens the evaluation designs of complex interventions. Moreover, it provides prudent evidence that the implementation of COPD disease management programmes can positively influence outcomes of care. PMID:20346135

GLIS1-3 transcription factors: critical roles in the regulation of multiple physiological processes and diseases.

PubMed

Jetten, Anton M

2018-05-19

Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions. Loss of GLIS3 function in humans and mice leads to the development of several pathologies, including neonatal diabetes and congenital hypothyroidism, polycystic kidney disease, and infertility. Single nucleotide polymorphisms in GLIS3 genes have been associated with increased risk of several diseases, including type 1 and type 2 diabetes, glaucoma, and neurological disorders. GLIS2 plays a critical role in the kidney and GLIS2 dysfunction leads to nephronophthisis, an end-stage, cystic renal disease. In addition, GLIS1-3 have regulatory functions in several stem/progenitor cell populations. GLIS1 and GLIS3 greatly enhance reprogramming efficiency of somatic cells into induced embryonic stem cells, while GLIS2 inhibits reprogramming. Recent studies have obtained substantial mechanistic insights into several physiological processes regulated by GLIS2 and GLIS3, while a little is still known about the physiological functions of GLIS1. The localization of some GLIS proteins to the primary cilium suggests that their activity may be regulated by a downstream primary cilium-associated signaling pathway. Insights into the upstream GLIS signaling pathway may provide opportunities for the development of new therapeutic strategies for diabetes, hypothyroidism, and other diseases.

The intricate mechanisms of neurodegeneration in prion diseases

PubMed Central

Soto, Claudio; Satani, Nikunj

2010-01-01

Prion diseases are a group of infectious neurodegenerative diseases with an entirely novel mechanism of transmission, involving a protein-only infectious agent that propagates the disease by transmitting protein conformational changes. The disease results from extensive and progressive brain degeneration. The molecular mechanisms involved in neurodegeneration are not entirely known but involve multiple processes operating simultaneously and synergistically in the brain, including spongiform degeneration, synaptic alterations, brain inflammation, neuronal death and the accumulation of protein aggregates. Here, we review the pathways implicated in prion-induced brain damage and put the pieces together into a possible model of neurodegeneration in prion disorders. A more comprehensive understanding of the molecular basis of brain degeneration is essential to develop a much needed therapy for these devastating diseases. PMID:20889378

A Tol2 Gateway-Compatible Toolbox for the Study of the Nervous System and Neurodegenerative Disease.

PubMed

Don, Emily K; Formella, Isabel; Badrock, Andrew P; Hall, Thomas E; Morsch, Marco; Hortle, Elinor; Hogan, Alison; Chow, Sharron; Gwee, Serene S L; Stoddart, Jack J; Nicholson, Garth; Chung, Roger; Cole, Nicholas J

2017-02-01

Currently there is a lack in fundamental understanding of disease progression of most neurodegenerative diseases, and, therefore, treatments and preventative measures are limited. Consequently, there is a great need for adaptable, yet robust model systems to both investigate elementary disease mechanisms and discover effective therapeutics. We have generated a Tol2 Gateway-compatible toolbox to study neurodegenerative disorders in zebrafish, which includes promoters for astrocytes, microglia and motor neurons, multiple fluorophores, and compatibility for the introduction of genes of interest or disease-linked genes. This toolbox will advance the rapid and flexible generation of zebrafish models to discover the biology of the nervous system and the disease processes that lead to neurodegeneration.

Matrix metalloproteinase inhibitors as investigative tools in the pathogenesis and management of vascular disease.

PubMed

Benjamin, Mina M; Khalil, Raouf A

2012-01-01

Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade various components of the extracellular matrix (ECM). MMPs could also regulate the activity of several non-ECM bioactive substrates and consequently affect different cellular functions. Members of the MMPs family include collagenases, gelatinases, stromelysins, matrilysins, membrane-type MMPs, and others. Pro-MMPs are cleaved into active MMPs, which in turn act on various substrates in the ECM and on the cell surface. MMPs play an important role in the regulation of numerous physiological processes including vascular remodeling and angiogenesis. MMPs may also be involved in vascular diseases such as hypertension, atherosclerosis, aortic aneurysm, and varicose veins. MMPs also play a role in the hemodynamic and vascular changes associated with pregnancy and preeclampsia. The role of MMPs is commonly assessed by measuring their gene expression, protein amount, and proteolytic activity using gel zymography. Because there are no specific activators of MMPs, MMP inhibitors are often used to investigate the role of MMPs in different physiologic processes and in the pathogenesis of specific diseases. MMP inhibitors include endogenous tissue inhibitors (TIMPs) and pharmacological inhibitors such as zinc chelators, doxycycline, and marimastat. MMP inhibitors have been evaluated as diagnostic and therapeutic tools in cancer, autoimmune disease, and cardiovascular disease. Although several MMP inhibitors have been synthesized and tested both experimentally and clinically, only one MMP inhibitor, i.e., doxycycline, is currently approved by the Food and Drug Administration. This is mainly due to the undesirable side effects of MMP inhibitors especially on the musculoskeletal system. While most experimental and clinical trials of MMP inhibitors have not demonstrated significant benefits, some trials still showed promising results. With the advent of new genetic and pharmacological tools, disease-specific MMP inhibitors with fewer undesirable effects are being developed and could be useful in the management of vascular disease.

A three-dimensional point process model for the spatial distribution of disease occurrence in relation to an exposure source.

PubMed

Grell, Kathrine; Diggle, Peter J; Frederiksen, Kirsten; Schüz, Joachim; Cardis, Elisabeth; Andersen, Per K

2015-10-15

We study methods for how to include the spatial distribution of tumours when investigating the relation between brain tumours and the exposure from radio frequency electromagnetic fields caused by mobile phone use. Our suggested point process model is adapted from studies investigating spatial aggregation of a disease around a source of potential hazard in environmental epidemiology, where now the source is the preferred ear of each phone user. In this context, the spatial distribution is a distribution over a sample of patients rather than over multiple disease cases within one geographical area. We show how the distance relation between tumour and phone can be modelled nonparametrically and, with various parametric functions, how covariates can be included in the model and how to test for the effect of distance. To illustrate the models, we apply them to a subset of the data from the Interphone Study, a large multinational case-control study on the association between brain tumours and mobile phone use. Copyright © 2015 John Wiley & Sons, Ltd.

Radiation injury to the temporal bone

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

Guida, R.A.; Finn, D.G.; Buchalter, I.H.

1990-01-01

Osteoradionecrosis of the temporal bone is an unusual sequela of radiation therapy to the head and neck. Symptoms occur many years after the radiation is administered, and progression of the disease is insidious. Hearing loss (sensorineural, conductive, or mixed), otalgia, otorrhea, and even gross tissue extrusion herald this condition. Later, intracranial complications such as meningitis, temporal lobe or cerebellar abscess, and cranial neuropathies may occur. Reported here are five cases of this rare malady representing varying degrees of the disease process. They include a case of radiation-induced necrosis of the tympanic ring with persistent squamous debris in the external auditorymore » canal and middle ear. Another case demonstrates the progression of radiation otitis media to mastoiditis with bony sequestration. Further progression of the disease process is seen in a third case that evolved into multiple cranial neuropathies from skull base destruction. Treatment includes systemic antibiotics, local wound care, and debridement in cases of localized tissue involvement. More extensive debridement with removal of sequestrations, abscess drainage, reconstruction with vascularized tissue from regional flaps, and mastoid obliteration may be warranted for severe cases. Hyperbaric oxygen therapy has provided limited benefit.« less

Molecular Pathological Epidemiology of Epigenetics: Emerging Integrative Science to Analyze Environment, Host, and Disease

PubMed Central

Ogino, Shuji; Lochhead, Paul; Chan, Andrew T.; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M.; Meyerhardt, Jeffrey A.; Meissner, Alexander; Schernhammer, Eva S.; Fuchs, Charles S.; Giovannucci, Edward

2013-01-01

Epigenetics acts as an interface between environmental / exogenous factors, cellular responses and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases, including non-neoplastic disorders (e.g., cardiovascular diseases, hypertension, diabetes mellitus, autoimmune diseases, and some infectious diseases) and neoplasms (e.g., leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc.) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. DNA methylation assays are widely applied to formalin-fixed paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiologic factors, cellular molecular characteristics, and disease evolution, the field of “Molecular Pathological Epidemiology (MPE)” has emerged as an interdisciplinary integration of “molecular pathology” and “epidemiology”, with a similar conceptual framework to systems biology and network medicine. In contrast to traditional epidemiologic research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle; that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macro-environment and tissue microenvironment. The widespread application of epigenomics (e.g., methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator phenotype, LINE-1 hypomethylation, etc.), and host-disease interactions. MPE may represent a logical evolution of GWAS, termed “GWAS-MPE approach”. Though epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. This article will illustrate increasing contribution of modern pathology to broader public health sciences, which attests pivotal roles of pathologists in the new integrated MPE science towards our ultimate goal of personalized medicine and prevention. PMID:23307060

Air pollution and Parkinson's disease - evidence and future directions.

PubMed

Palacios, Natalia

2017-12-20

Parkinson's disease (PD) is a neurodegenerative disease of unknown etiology that is thought to be caused by a complex combination of environmental and/or genetic factors. Air pollution exposure is linked to numerous adverse effects on human health, including brain inflammation and oxidative stress, processes that are believed to contribute to the development and progression of PD. This review provides an overview of recent advances in the epidemiology of air pollution and PD, including evidence of the effects of various pollutants (ozone, PM10, PM2.5, PM2.5-10, NOx, NO2, CO, traffic air pollution, second-hand smoking) on PD risk. Based on this evidence, promising opportunities for future research are outlined, including: (1) studies of smaller particle sizes that cross the blood-brain barrier, (2) studies of the effects of air pollution on PD mortality and/or progression; (3) studies of interactions of air pollution with gene environment and other environmental factors.

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

Neurological and Psychiatric Diseases and Their Unique Cognitive Profiles: Implications for Nursing Practice and Research

PubMed Central

Vance, David E.; Dodson, Joan E.; Watkins, Jason; Kennedy, Bridgett H.; Keltner, Norman L.

2013-01-01

To successfully negotiate and interact with one’s environment, optimal cognitive functioning is needed. Unfortunately, many neurological and psychiatric diseases impede certain cognitive abilities such as executive functioning or speed of processing; this can produce a poor fit between the patient and the cognitive demands of his or her environment. Such non-dementia diseases include bipolar disorder, schizophrenia, post-traumatic stress syndrome, depression, and anxiety disorders, just to name a few. Each of these diseases negatively affects particular areas of the brain, resulting in distinct cognitive profiles (e.g., deficits in executive functioning but normal speed of processing as seen in schizophrenia). In fact, it is from these cognitive deficits in which such behavioral and emotional symptoms may manifest (e.g., delusions, paranoia). This article highlights the distinct cognitive profiles of such common neurological and psychiatric diseases. An understanding of such disease-specific cognitive profiles can assist nurses in providing care to patients by knowing what cognitive deficits are associated with each disease and how these cognitive deficits impact everyday functioning and social interactions. Implications for nursing practice and research are posited within the framework of cognitive reserve and neuroplasticity. PMID:23422693

New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases

PubMed Central

Adachi, Naoki; Numakawa, Tadahiro; Richards, Misty; Nakajima, Shingo; Kunugi, Hiroshi

2014-01-01

Brain-derived neurotrophic factor (BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has been reported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer’s disease, Huntington’s disease, depression and schizophrenia. PMID:25426265

Rituximab for the treatment of refractory simultaneous anti-glomerular basement membrane (anti-GBM) and membranous nephropathy.

PubMed

Bandak, Ghassan; Jones, Bruce A; Li, Jian; Yee, Jerry; Umanath, Kausik

2014-02-01

Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs rarely in the presence of another B-cell disorder, membranous nephropathy. The coexistence of these two autoimmune disorders would be anticipated to require differing, specific therapies targeted to each disease process. We describe a case of concomitant membranous nephropathy and anti-GBM disease in which conventional therapy, including steroids, plasmapheresis and cyclophosphamide, failed to attenuate the anti-GBM disease, yet responded to an alternative treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody treatment substantially reduced anti-GBM antibody titers and led to discontinuation of plasmapheresis, while maintaining the remission of membranous nephropathy and anti-GBM disease.

Disorders of emotional processing in amyotrophic lateral sclerosis.

PubMed

Sedda, Anna

2014-12-01

Amyotrophic lateral sclerosis (ALS) is a degenerative brain disease characterized by motor, behavioural and cognitive deficits. Only recently, emotional processing disorders have been shown in this disease. The interest in affective processing in ALS is growing given that basic emotion impairments could impact copying strategies and mood. Studies explore both basic emotion recognition and social cognition. Results are congruent on arousal and valence detection impairments, independently from the stimulus modality (verbal or visual). Further, recognition of facial expressions of anger, sadness and disgust is impaired in ALS, even when cognition is preserved. Clinical features such as type of onset and severity of the disease could be the cause of the heterogeneity in emotional deficits profiles between patients. Finally, a study employing diffusion tensor imaging showed that emotional dysfunctions in ALS are related to right hemispheric connective bundles impairments, involving the inferior longitudinal fasciculus and the inferior frontal occipital fasciculus. Research on emotional processing in ALS is still in its infancy and results are mixed. Future research including more detailed clinical profiles of patients and measures of brain connectivity will provide useful information to understand heterogeneity of results in ALS.

The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms.

PubMed

Lin, Wei-Jye; Salton, Stephen R

2013-01-01

The regulated secretory pathway provides critical control of peptide, growth factor, and hormone release from neuroendocrine and endocrine cells, and neurons, maintaining physiological homeostasis. Propeptides and prohormones are packaged into dense core granules (DCGs), where they frequently undergo tissue-specific processing as the DCG matures. Proteins of the granin family are DCG components, and although their function is not fully understood, data suggest they are involved in DCG formation and regulated protein/peptide secretion, in addition to their role as precursors of bioactive peptides. Association of gene variation, including single nucleotide polymorphisms (SNPs), with neuropsychiatric, endocrine, and metabolic diseases, has implicated specific secreted proteins and peptides in disease pathogenesis. For example, a SNP at position 196 (G/A) of the human brain-derived neurotrophic factor gene dysregulates protein processing and secretion and leads to cognitive impairment. This suggests more generally that variants identified in genes encoding secreted growth factors, peptides, hormones, and proteins involved in DCG biogenesis, protein processing, and the secretory apparatus, could provide insight into the process of regulated secretion as well as disorders that result when it is impaired.

The Regulated Secretory Pathway and Human Disease: Insights from Gene Variants and Single Nucleotide Polymorphisms

PubMed Central

Lin, Wei-Jye; Salton, Stephen R.

2013-01-01

The regulated secretory pathway provides critical control of peptide, growth factor, and hormone release from neuroendocrine and endocrine cells, and neurons, maintaining physiological homeostasis. Propeptides and prohormones are packaged into dense core granules (DCGs), where they frequently undergo tissue-specific processing as the DCG matures. Proteins of the granin family are DCG components, and although their function is not fully understood, data suggest they are involved in DCG formation and regulated protein/peptide secretion, in addition to their role as precursors of bioactive peptides. Association of gene variation, including single nucleotide polymorphisms (SNPs), with neuropsychiatric, endocrine, and metabolic diseases, has implicated specific secreted proteins and peptides in disease pathogenesis. For example, a SNP at position 196 (G/A) of the human brain-derived neurotrophic factor gene dysregulates protein processing and secretion and leads to cognitive impairment. This suggests more generally that variants identified in genes encoding secreted growth factors, peptides, hormones, and proteins involved in DCG biogenesis, protein processing, and the secretory apparatus, could provide insight into the process of regulated secretion as well as disorders that result when it is impaired. PMID:23964269

Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease.

PubMed

Bekris, Lynn M; Tsuang, Debby W; Peskind, Elaine R; Yu, Chang E; Montine, Thomas J; Zhang, Jing; Zabetian, Cyrus P; Leverenz, James B

2015-06-01

Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD). Parkinson's disease (n = 86) and control (n = 161) DNA were genotyped for 19 regulatory region tagging single-nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 status. Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344). In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.

DISINFECTION

EPA Science Inventory

The primary goal of the disinfection process in drinking water treatment is the inactivation of microbial pathogens. These pathogens comprise a diverse group of organisms which serve as the etiological agents of waterborne disease. Included in this group are bacterial, viral and ...

Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease.

PubMed

Gupta, Arjun; Ayyar, Balaji; Zia, Hamid; Chen, Weina; Harris, Samar; Naina, Harris V

2016-06-01

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease.

Emotional and cognitive social processes are impaired in Parkinson's disease and are related to behavioral disorders.

PubMed

Narme, Pauline; Mouras, Harold; Roussel, Martine; Duru, Cécile; Krystkowiak, Pierre; Godefroy, Olivier

2013-03-01

Parkinson's disease (PD) is associated with behavioral disorders that can affect social functioning but are poorly understood. Since emotional and cognitive social processes are known to be crucial in social relationships, impairment of these processes may account for the emergence of behavioral disorders. We used a systematic battery of tests to assess emotional processes and social cognition in PD patients and relate our findings to conventional neuropsychological data (especially behavioral disorders). Twenty-three PD patients and 46 controls (matched for age and educational level) were included in the study and underwent neuropsychological testing, including an assessment of the behavioral and cognitive components of executive function. Emotional and cognitive social processes were assessed with the Interpersonal Reactivity Index caregiver-administered questionnaire (as a measure of empathy), a facial emotion recognition task and two theory of mind (ToM) tasks. When compared with controls, PD patients showed low levels of empathy (p = .006), impaired facial emotion recognition (which persisted after correction for perceptual abilities) (p = .001), poor performance in a second-order ToM task (p = .008) that assessed both cognitive (p = .004) and affective (p = .03) inferences and, lastly, frequent dysexecutive behavioral disorders (in over 40% of the patients). Overall, impaired emotional and cognitive social functioning was observed in 17% of patients and was related to certain cognitive dysexecutive disorders. In terms of behavioral dysexecutive disorders, social behavior disorders were related to impaired emotional and cognitive social functioning (p = .04) but were independent of cognitive impairments. Emotional and cognitive social processes were found to be impaired in Parkinson's disease. This impairment may account for the emergence of social behavioral disorders. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Nanoparticle based tailoring of adjuvant function: the role in vaccine development.

PubMed

Prashant, Chandravilas Keshvan; Kumar, Manoj; Dinda, Amit Kumar

2014-09-01

Vaccination is one of the most powerful therapeutic tools for prevention and management of various infective and non-infective diseases including malignancy. Mass vaccination is a great strategy for eradicating major infectious diseases throughout the world like small pox. Application of nanotechnology for antigen delivery is a unique area of research and development which can change the vaccination strategy and policy in future. Nanocarriers can enhance antigen presentation including modulation of antigen processing pathways according to the specific need. The current review explores the pros and cons of application of different nanomaterials for antigen presentation and vaccine development.

An Evidence-Based Practical Approach to Pediatric Otolaryngology in the Developing World.

PubMed

Belcher, Ryan H; Molter, David W; Goudy, Steven L

2018-06-01

Despite humanitarian otolaryngology groups traveling in record numbers to resource-limited areas treating pediatric otolaryngology disease processes and training local providers, there remains a large burden of unmet needs. There is a meager amount of published information that comes from the developing world from an otolaryngology standpoint. As would be expected, the little information that does comes involves some of the most common pediatric otolaryngology diseases and surgical burdens including childhood hearing loss, otitis media, adenotonsillectomies, airway obstructions requiring tracheostomies, foreign body aspirations, and craniomaxillofacial surgeries, including cleft lip and palate. Copyright © 2018 Elsevier Inc. All rights reserved.

Tracheomalacia and tracheobronchomalacia in children and adults: an in-depth review.

PubMed

Carden, Kelly A; Boiselle, Philip M; Waltz, David A; Ernst, Armin

2005-03-01

Tracheomalacia and tracheobronchomalacia are disorders that are encountered in both pediatric and adult medicine. Despite increasing recognition of these disease processes, there remains some uncertainty regarding their identification, causes, and treatment. This article is intended to be a comprehensive review of both the adult and pediatric forms of the diseases, and includes sections on the historical aspects of the disorders, and their classification, associated conditions, histopathology, and natural history. We also review the various modalities that are used for diagnosis as well as the state of the art of treatment, including airway stent placement and surgical intervention.

Learning and using technology in intertwined processes: a study of people with mild cognitive impairment or Alzheimer's disease.

PubMed

Rosenberg, Lena; Nygård, Louise

2014-09-01

People with mild cognitive impairment and Alzheimer's disease are likely to be challenged by the multitude of everyday technology in today's society. The aim of this study was to explore how they try to prohibit, avoid or solve problems in everyday technology use, maintain skills, and learn to use new technology. To explore how the participants applied and reasoned about using everyday technology in real-life situations interviews were conducted while the participants used their own technology in their homes. Interviews were conducted with 20 participants with mild cognitive impairment (n = 10) or Alzheimer's disease (n = 10). The analyses were inspired from grounded theory and resulted in one core category and three sub-categories that represent sub-processes in the core. The core finding presents a continuous, intertwined process of learning and using everyday technology, highlighting how the context was interwoven in the processes. The participants used a rich variety of management strategies when approaching technology, including communication with the everyday technologies on different levels. The findings underscore that it is important to support continued use of everyday technology as long as it is valued and relevant to the person with mild cognitive impairment or Alzheimer's disease. The intertwined process of learning and using everyday technology suggests how support could target different sub-processes. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Morphology and physiology of the olfactory system of blood-feeding insects.

PubMed

Guidobaldi, F; May-Concha, I J; Guerenstein, P G

2014-01-01

Several blood-feeding (hematophagous) insects are vectors of a number of diseases including dengue, Chagas disease and leishmaniasis which persistently affect public health throughout Latin America. The vectors of those diseases include mosquitoes, triatomine bugs and sandflies. As vector control is an efficient way to prevent these illnesses it is important to understand the sensory biology of those harmful insects. We study the physiology of the olfactory system of those insects and apply that knowledge on the development of methods to manipulate their behavior. Here we review some of the latest information on insect olfaction with emphasis on hematophagous insects. The insect olfactory sensory neurons are housed inside hair-like organs called sensilla which are mainly distributed on the antenna and mouthparts. The identity of many of the odor compounds that those neurons detect are already known in hematophagous insects. They include several constituents of host (vertebrate) odor, sex, aggregation and alarm pheromones, and compounds related to egg-deposition behavior. Recent work has contributed significant knowledge on how odor information is processed in the insect first odor-processing center in the brain, the antennal lobe. The quality, quantity, and temporal features of the odor stimuli are encoded by the neural networks of the antennal lobe. Information regarding odor mixtures is also encoded. While natural mixtures evoke strong responses, synthetic mixtures that deviate from their natural counterparts in terms of key constituents or proportions of those constituents evoke weaker responses. The processing of olfactory information is largely unexplored in hematophagous insects. However, many aspects of their olfactory behavior are known. As in other insects, responses to relevant single odor compounds are weak while natural mixtures evoke strong responses. Future challenges include studying how information about odor mixtures is processed in their brain. This could help develop highly attractive synthetic odor blends to lure them into traps. Copyright © 2014 Elsevier Ltd. All rights reserved.

Animal models of aging research: implications for human aging and age-related diseases.

PubMed

Mitchell, Sarah J; Scheibye-Knudsen, Morten; Longo, Dan L; de Cabo, Rafael

2015-01-01

Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research.

[Diagnostic and curative bronchoscopy for purulent-destructive pulmonary diseases].

PubMed

Pinchuk, T P; Yasnogorodsky, O O; Guryanova, Yu V; Taldykin, M V; Kachikin, A S; Catane, Yu A

To assess an efficacy of diagnostic and curative bronchoscopy in patients with purulent-destructive pulmonary diseases. Diagnosis and treatment of 34 patients with purulent-destructive pulmonary diseases including small-focal destruction (14) and lung abscesses (19) were analyzed. 33 patients underwent diagnostic fibrobronchoscopy (FBS) with brush and transbronchial biopsy. Curative endoscopy included bronchial tree sanation, peribronchial administration of antibiotics (5) and transbronchial drainage of abscess (14). Atrophic bronchitis and cicatricial deformity of the 2-3rd segmental bronchi were revealed in 81.8% and 15.2% respectively. Transbronchial biopsy confirmed malignant neoplasms (15.2%) and pulmonary tuberculosis (6.1%). Peribronchial administration of amikacin in patients with small-focal pulmonary destruction and transbronchial drainage of abscesses accelerated pulmonary tissue repair and complete recovery. Transbronchial biopsy in patients with destructive pulmonary diseases verifies pathological process and excludes malignant and specific pulmonary damage. Complex use of endoscopic methods is associated with positive clinical result in all patients with pulmonary destruction.

Veterinary clinical nutrition: success stories: an overview.

PubMed

Davies, Mike

2016-08-01

In this overview of success stories in veterinary clinical nutrition topics in cats and dogs reviewed include the dietary management of chronic kidney disease, dissolution of urinary tract uroliths by dietary modification, the recognition that taurine and L-carnitine deficiencies can cause dilated cardiomyopathy; that clinical signs associated with feline hyperthyroidism (caused by a benign adenoma) can be controlled by a low-iodine diet alone; that dietary management of canine osteoarthritis can also reduce non-steroidal anti-inflammatory drug doses; and that disease-free intervals and survival times can be statistically longer in dogs with Stage III lymphoma managed with diet. As we discover more about nutrigenetics and nutrigenomics, and as we expand our basic understanding of idiopathic diseases we are bound to identify more nutritionally related causes, and be able to develop novel dietary strategies to manage disease processes, including the formulation of diets designed to alter gene expression to obtain beneficial clinical outcomes.

The Screening of Genes Sensitive to Long-Term, Low-Level Microwave Exposure and Bioinformatic Analysis of Potential Correlations to Learning and Memory.

PubMed

Zhao, Ya Li; Li, Ying Xian; Ma, Hong Bo; Li, Dong; Li, Hai Liang; Jiang, Rui; Kan, Guang Han; Yang, Zhen Zhong; Huang, Zeng Xin

2015-08-01

To gain a better understanding of gene expression changes in the brain following microwave exposure in mice. This study hopes to reveal mechanisms contributing to microwave-induced learning and memory dysfunction. Mice were exposed to whole body 2100 MHz microwaves with specific absorption rates (SARs) of 0.45 W/kg, 1.8 W/kg, and 3.6 W/kg for 1 hour daily for 8 weeks. Differentially expressing genes in the brains were screened using high-density oligonucleotide arrays, with genes showing more significant differences further confirmed by RT-PCR. The gene chip results demonstrated that 41 genes (0.45 W/kg group), 29 genes (1.8 W/kg group), and 219 genes (3.6 W/kg group) were differentially expressed. GO analysis revealed that these differentially expressed genes were primarily involved in metabolic processes, cellular metabolic processes, regulation of biological processes, macromolecular metabolic processes, biosynthetic processes, cellular protein metabolic processes, transport, developmental processes, cellular component organization, etc. KEGG pathway analysis showed that these genes are mainly involved in pathways related to ribosome, Alzheimer's disease, Parkinson's disease, long-term potentiation, Huntington's disease, and Neurotrophin signaling. Construction of a protein interaction network identified several important regulatory genes including synbindin (sbdn), Crystallin (CryaB), PPP1CA, Ywhaq, Psap, Psmb1, Pcbp2, etc., which play important roles in the processes of learning and memorye. Long-term, low-level microwave exposure may inhibit learning and memory by affecting protein and energy metabolic processes and signaling pathways relating to neurological functions or diseases. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

High bioavailability curcumin: an anti-inflammatory and neurosupportive bioactive nutrient for neurodegenerative diseases characterized by chronic neuroinflammation.

PubMed

Ullah, Faheem; Liang, Andy; Rangel, Alejandra; Gyengesi, Erika; Niedermayer, Garry; Münch, Gerald

2017-04-01

Neuroinflammation is a pathophysiological process present in a number of neurodegenerative disorders, such as Alzheimer's disease, Huntington's disease, Parkinson's disease, stroke, traumatic brain injury including chronic traumatic encephalopathy and other age-related CNS disorders. Although there is still much debate about the initial trigger for some of these neurodegenerative disorders, during the progression of disease, broad range anti-inflammatory drugs including cytokine suppressive anti-inflammatory drugs (CSAIDs) might be promising therapeutic options to limit neuroinflammation and improve the clinical outcome. One of the most promising CSAIDs is curcumin, which modulates the activity of several transcription factors (e.g., STAT, NF-κB, AP-1) and their pro-inflammatory molecular signaling pathways. However, normal curcumin preparations demonstrate low bioavailability in vivo. To increase bioavailability, preparations of high bioavailability curcumin have been introduced to achieve therapeutically relevant concentrations in target tissues. This literature review aims to summarize the pharmacokinetic and toxicity profile of different curcumin formulations.

Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility.

PubMed

Magyari, Lili; Kovesdi, Erzsebet; Sarlos, Patricia; Javorhazy, Andras; Sumegi, Katalin; Melegh, Bela

2014-03-28

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), represents a group of chronic inflammatory disorders caused by dysregulated immune responses in genetically predisposed individuals. Genetic markers are associated with disease phenotype and long-term evolution, but their value in everyday clinical practice is limited at the moment. IBD has a clear immunological background and interleukins play key role in the process. Almost 130 original papers were revised including meta-analysis. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but text often do not available for the doctors use these in the clinical practice nowadays. We conducted a systematic review of the current literature on interleukin and interleukin receptor gene polymorphisms associated with IBD, performing an electronic search of PubMed Database from publications of the last 10 years, and used the following medical subject heading terms and/or text words: IBD, CD, UC, interleukins and polymorphisms.

Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility

PubMed Central

Magyari, Lili; Kovesdi, Erzsebet; Sarlos, Patricia; Javorhazy, Andras; Sumegi, Katalin; Melegh, Bela

2014-01-01

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), represents a group of chronic inflammatory disorders caused by dysregulated immune responses in genetically predisposed individuals. Genetic markers are associated with disease phenotype and long-term evolution, but their value in everyday clinical practice is limited at the moment. IBD has a clear immunological background and interleukins play key role in the process. Almost 130 original papers were revised including meta-analysis. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but text often do not available for the doctors use these in the clinical practice nowadays. We conducted a systematic review of the current literature on interleukin and interleukin receptor gene polymorphisms associated with IBD, performing an electronic search of PubMed Database from publications of the last 10 years, and used the following medical subject heading terms and/or text words: IBD, CD, UC, interleukins and polymorphisms. PMID:24695754

From miracle to reconciliation: a hermeneutic phenomenological study exploring the experience of living with Parkinson's disease following deep brain stimulation.

PubMed

Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen

2010-10-01

Deep Brain Stimulation for Parkinson's disease is a promising treatment for patients who can no longer be treated satisfactorily with L-dopa. Deep Brain Stimulation is known to relieve motor symptoms of Parkinson's disease and improve quality of life. Focusing on how patients experience life when treated with Deep Brain Stimulation can provide essential information on the process patients go through when receiving a treatment that alters the body and changes the illness trajectory. The aim of this study was to explore and describe the experience of living with Parkinson's disease when treated with Deep Brain Stimulation. The study was designed as a longitudinal study and data were gathered through qualitative in-depth interviews three times during the first year of treatment. Nine patients participated in the study. They were included when they had accepted treatment with Deep Brain Stimulation for Parkinson's disease. Data collection and data analysis were inspired by the hermeneutic phenomenological methodology of Van Manen. The treatment had a major impact on the body. Participants experienced great bodily changes and went through a process of adjustment in three phases during the first year of treatment with Deep Brain Stimulation. These stages were; being liberated: a kind of miracle, changes as a challenge: decline or opportunity and reconciliation: re-defining life with Parkinson's disease. The course of the process was unique for each participant, but dominant was that difficulties during the adjustment of stimulation and medication did affect the re-defining process. Patients go through a dramatic process of change following Deep Brain Stimulation. A changing body affects their entire lifeworld. Some adjust smoothly to changes while others are affected by loss of control, uncertainty and loss of everyday life as they knew it. These experiences affect the process of adjusting to life with Deep Brain Stimulation and re-define life with Parkinson's disease. It is of significant importance that health care professionals are aware of these dramatic changes in the patients' life and offer support during the adjustment process following Deep Brain Stimulation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

The periodontal – endodontic continuum: A review

PubMed Central

Sunitha V, Raja; Emmadi, Pamela; Namasivayam, Ambalavanan; Thyegarajan, Ramakrishnan; Rajaraman, Vijayalakshmi

2008-01-01

Periodontal therapy deals with many aspects of the supporting structures, including the prevention and repair of lesions of the gingival sulcus. Endodontics deals primarily with disease of the pulp and periapical tissues. The success of both periodontal and endodontic therapy depends on the elimination of both disease processes, whether they exist separately or as a combined lesion. The relationship between periodontal and endodontic disease has been a subject of speculation for many years. This paper aims at presenting a comprehensive review of several aspects of perio-endo lesions. PMID:20142886

Endothelial microvesicles in hypoxic hypoxia diseases.

PubMed

Deng, Fan; Wang, Shuang; Xu, Riping; Yu, Wenqian; Wang, Xianyu; Zhang, Liangqing

2018-05-29

Hypoxic hypoxia, including abnormally low partial pressure of inhaled oxygen, external respiratory dysfunction-induced respiratory hypoxia and venous blood flow into the arterial blood, is characterized by decreased arterial oxygen partial pressure, resulting in tissue oxygen deficiency. The specific characteristics include reduced arterial oxygen partial pressure and oxygen content. Hypoxic hypoxia diseases (HHDs) have attracted increased attention due to their high morbidity and mortality and mounting evidence showing that hypoxia-induced oxidative stress, coagulation, inflammation and angiogenesis play extremely important roles in the physiological and pathological processes of HHDs-related vascular endothelial injury. Interestingly, endothelial microvesicles (EMVs), which can be induced by hypoxia, hypoxia-induced oxidative stress, coagulation and inflammation in HHDs, have emerged as key mediators of intercellular communication and cellular functions. EMVs shed from activated or apoptotic endothelial cells (ECs) reflect the degree of ECs damage, and elevated EMVs levels are present in several HHDs, including obstructive sleep apnoea syndrome and chronic obstructive pulmonary disease. Furthermore, EMVs have procoagulant, proinflammatory and angiogenic functions that affect the pathological processes of HHDs. This review summarizes the emerging roles of EMVs in the diagnosis, staging, treatment and clinical prognosis of HHDs. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Systematic review of electronic surveillance of infectious diseases with emphasis on antimicrobial resistance surveillance in resource-limited settings.

PubMed

Rattanaumpawan, Pinyo; Boonyasiri, Adhiratha; Vong, Sirenda; Thamlikitkul, Visanu

2018-02-01

Electronic surveillance of infectious diseases involves rapidly collecting, collating, and analyzing vast amounts of data from interrelated multiple databases. Although many developed countries have invested in electronic surveillance for infectious diseases, the system still presents a challenge for resource-limited health care settings. We conducted a systematic review by performing a comprehensive literature search on MEDLINE (January 2000-December 2015) to identify studies relevant to electronic surveillance of infectious diseases. Study characteristics and results were extracted and systematically reviewed by 3 infectious disease physicians. A total of 110 studies were included. Most surveillance systems were developed and implemented in high-income countries; less than one-quarter were conducted in low-or middle-income countries. Information technologies can be used to facilitate the process of obtaining laboratory, clinical, and pharmacologic data for the surveillance of infectious diseases, including antimicrobial resistance (AMR) infections. These novel systems require greater resources; however, we found that using electronic surveillance systems could result in shorter times to detect targeted infectious diseases and improvement of data collection. This study highlights a lack of resources in areas where an effective, rapid surveillance system is most needed. The availability of information technology for the electronic surveillance of infectious diseases, including AMR infections, will facilitate the prevention and containment of such emerging infectious diseases. Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

A peer review process as part of the implementation of clinical pathways in radiation oncology: Does it improve compliance?

PubMed

Gebhardt, Brian J; Heron, Dwight E; Beriwal, Sushil

Clinical pathways are patient management plans that standardize evidence-based practices to ensure high-quality and cost-effective medical care. Implementation of a pathway is a collaborative process in our network, requiring the active involvement of physicians. This approach promotes acceptance of pathway recommendations, although a peer review process is necessary to ensure compliance and to capture and approve off-pathway selections. We investigated the peer review process and factors associated with time to completion of peer review. Our cancer center implemented radiation oncology pathways for every disease site throughout a large, integrated network. Recommendations are written based upon national guidelines, published literature, and institutional experience with evidence evaluated hierarchically in order of efficacy, toxicity, and then cost. Physicians enter decisions into an online, menu-driven decision support tool that integrates with medical records. Data were collected from the support tool and included the rate of on- and off-pathway selections, peer review decisions performed by disease site directors, and time to complete peer review. A total of 6965 treatment decisions were entered in 2015, and 605 (8.7%) were made off-pathway and were subject to peer review. The median time to peer review decision was 2 days (interquartile range, 0.2-6.8). Factors associated with time to peer review decision >48 hours on univariate analysis include disease site (P < .0001) with a trend toward significance (P = .066) for radiation therapy modality. There was no difference between recurrent and non-recurrent disease (P = .267). Multivariable analysis revealed disease site was associated with time to peer review (P < .001), with lymphoma and skin/sarcoma most strongly influencing decision time >48 hours. Clinical pathways are an integral tool for standardizing evidence-based care throughout our large, integrated network, with 91.3% of all treatment decisions being made as per pathway. The peer review process was feasible, with <1% selections ultimately rejected, suggesting that awareness of peer review of treatment decisions encourages compliance with clinical pathway recommendations. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

The mourning-liberation process in health and disease.

PubMed

Pollock, G H

1987-09-01

In this article I have presented my own research on the mourning-liberation process and related it to some of the ongoing work as well as past pioneering clinical studies of this adaptational process. Included in the references at the end of this paper is a listing of my published works on the mourning research, in chronologic order, for those who may wish to study aspects of what has been reported in greater detail.

The emerging roles of β-arrestins in fibrotic diseases

PubMed Central

Gu, Yuan-jing; Sun, Wu-yi; Zhang, Sen; Wu, Jing-jing; Wei, Wei

2015-01-01

β-Arrestins and β-arrestin2 are important adaptor proteins and signal transduction proteins that are mainly involved in the desensitization and internalization of G-protein-coupled receptors. Fibrosis is characterized by accumulation of excess extracellular matrix (ECM) molecules caused by chronic tissue injury. If highly progressive, the fibrotic process leads to organ malfunction and, eventually, death. The incurable lung fibrosis, renal fibrosis and liver fibrosis are among the most common fibrotic diseases. Recent studies show that β-arrestins can activate signaling cascades independent of G-protein activation and scaffold many intracellular signaling networks by diverse types of signaling pathways, including the Hedgehog, Wnt, Notch and transforming growth factor-β pathways, as well as downstream kinases such as MAPK and PI3K. These signaling pathways are involved in the pathological process of fibrosis and fibrotic diseases. This β-arrestin-mediated regulation not only affects cell growth and apoptosis, but also the deposition of ECM, activation of inflammatory response and development of fibrotic diseases. In this review, we survey the involvement of β-arrestins in various signaling pathways and highlight different aspects of their regulation of fibrosis. We also discuss the important roles of β-arrestins in the process of fibrotic diseases by regulating the inflammation and deposit of ECM. It is becoming more evident that targeting β-arrestins may offer therapeutic potential for the treatment of fibrotic diseases. PMID:26388156

Auditory post-processing in a passive listening task is deficient in Alzheimer's disease.

PubMed

Bender, Stephan; Bluschke, Annet; Dippel, Gabriel; Rupp, André; Weisbrod, Matthias; Thomas, Christine

2014-01-01

To investigate whether automatic auditory post-processing is deficient in patients with Alzheimer's disease and is related to sensory gating. Event-related potentials were recorded during a passive listening task to examine the automatic transient storage of auditory information (short click pairs). Patients with Alzheimer's disease were compared to a healthy age-matched control group. A young healthy control group was included to assess effects of physiological aging. A bilateral frontal negativity in combination with deep temporal positivity occurring 500 ms after stimulus offset was reduced in patients with Alzheimer's disease, but was unaffected by physiological aging. Its amplitude correlated with short-term memory capacity, but was independent of sensory gating in healthy elderly controls. Source analysis revealed a dipole pair in the anterior temporal lobes. Results suggest that auditory post-processing is deficient in Alzheimer's disease, but is not typically related to sensory gating. The deficit could neither be explained by physiological aging nor by problems in earlier stages of auditory perception. Correlations with short-term memory capacity and executive control tasks suggested an association with memory encoding and/or overall cognitive control deficits. An auditory late negative wave could represent a marker of auditory working memory encoding deficits in Alzheimer's disease. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl.

PubMed

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl

PubMed Central

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent. PMID:22787387

[Quality indicators for National Disease Management Guidelines using the example of the National Disease Management Guideline for "Chronic Heart Failure"].

PubMed

Nothacker, Monika Judith; Langer, Thomas; Weinbrenner, Susanne

2011-01-01

Together with an expert committee a structured approach to determining quality indicators for National Disease Management Guidelines has been developed. The key steps of this approach include: introducing guideline authors to the methodology at an early stage of the process of guideline development, pre-selecting recommendations of the guideline which are potentially measurable by means of quality indicators, assessing the potentially measurable quality indicators in written form using five criteria (including their importance for the health care system and clarity of definitions) and approving them in a formal consensus process. For lack of a database these quality indicators must be regarded as preliminary. For the National Disease Management Guideline "Chronic Heart Failure" nine rate-based indicators have been chosen. The indicators correspond to important strong recommendations (grade of recommendation: A) from the fields of diagnosis (two), general therapeutic strategy (two), specific treatment (three), clinical monitoring (one) and co-ordination of care (one). In a second step, the quality indicators have to be validated within a pilot project. The determination and assessment of the potential quality indicators have revealed room for improvement of guideline development. In particular, there is a need for more health care data and for specification of recommendations.

Apple phytochemicals and their health benefits

PubMed Central

Boyer, Jeanelle; Liu, Rui Hai

2004-01-01

Evidence suggests that a diet high in fruits and vegetables may decrease the risk of chronic diseases, such as cardiovascular disease and cancer, and phytochemicals including phenolics, flavonoids and carotenoids from fruits and vegetables may play a key role in reducing chronic disease risk. Apples are a widely consumed, rich source of phytochemicals, and epidemiological studies have linked the consumption of apples with reduced risk of some cancers, cardiovascular disease, asthma, and diabetes. In the laboratory, apples have been found to have very strong antioxidant activity, inhibit cancer cell proliferation, decrease lipid oxidation, and lower cholesterol. Apples contain a variety of phytochemicals, including quercetin, catechin, phloridzin and chlorogenic acid, all of which are strong antioxidants. The phytochemical composition of apples varies greatly between different varieties of apples, and there are also small changes in phytochemicals during the maturation and ripening of the fruit. Storage has little to no effect on apple phytochemicals, but processing can greatly affect apple phytochemicals. While extensive research exists, a literature review of the health benefits of apples and their phytochemicals has not been compiled to summarize this work. The purpose of this paper is to review the most recent literature regarding the health benefits of apples and their phytochemicals, phytochemical bioavailability and antioxidant behavior, and the effects of variety, ripening, storage and processing on apple phytochemicals. PMID:15140261

RNA G-quadruplexes: emerging mechanisms in disease

PubMed Central

Cammas, Anne

2017-01-01

Abstract RNA G-quadruplexes (G4s) are formed by G-rich RNA sequences in protein-coding (mRNA) and non-coding (ncRNA) transcripts that fold into a four-stranded conformation. Experimental studies and bioinformatic predictions support the view that these structures are involved in different cellular functions associated to both DNA processes (telomere elongation, recombination and transcription) and RNA post-transcriptional mechanisms (including pre-mRNA processing, mRNA turnover, targeting and translation). An increasing number of different diseases have been associated with the inappropriate regulation of RNA G4s exemplifying the potential importance of these structures on human health. Here, we review the different molecular mechanisms underlying the link between RNA G4s and human diseases by proposing several overlapping models of deregulation emerging from recent research, including (i) sequestration of RNA-binding proteins, (ii) aberrant expression or localization of RNA G4-binding proteins, (iii) repeat associated non-AUG (RAN) translation, (iv) mRNA translational blockade and (v) disabling of protein–RNA G4 complexes. This review also provides a comprehensive survey of the functional RNA G4 and their mechanisms of action. Finally, we highlight future directions for research aimed at improving our understanding on RNA G4-mediated regulatory mechanisms linked to diseases. PMID:28013268

Evaluation of a large scale implementation of disease management programmes in various Dutch regions: a study protocol

PubMed Central

2011-01-01

Background Disease management programmes (DMPs) have been developed to improve effectiveness and economic efficiency within chronic care delivery by combining patient-related, professional-directed, and organisational interventions. The benefits of DMPs within different settings, patient groups, and versions remain unclear. In this article we propose a protocol to evaluate a range of current DMPs by capturing them in a single conceptual framework, employing comparable structure, process, and outcome measures, and combining qualitative and quantitative research methods. Methods To assess DMP effectiveness a practical clinical trial will be conducted. Twenty-two disease management experiments will be studied in various Dutch regions consisting of a variety of collaborations between organisations and/or professionals. Patient cohorts include those with cardiovascular diseases, chronic obstructive pulmonary disease, diabetes, stroke, depression, psychotic diseases, and eating disorders. Our methodological approach combines qualitative and quantitative research methods to enable a comprehensive evaluation of complex programmes. Process indicators will be collected from health care providers' data registries and measured via physician and staff questionnaires. Patient questionnaires include health care experiences, health care utilisation, and quality of life. Qualitative data will be gathered by means of interviews and document analysis for an in depth description of project interventions and the contexts in which DMPs are embedded, and an ethnographic process evaluation in five DMPs. Such a design will provide insight into ongoing DMPs and demonstrate which elements of the intervention are potentially (cost)-effective for which patient populations. It will also enable sound comparison of the results of the different programmes. Discussion The study will lead to a better understanding of (1) the mechanisms of disease management, (2) the feasibility, and cost-effectiveness of a disease management approach to improving health care, and (3) the factors that determine success and failure of DMPs. Our study results will be relevant to decision makers and managers who confront the challenge of implementing and integrating DMPs into the health care system. Moreover, it will contribute to the search for methods to evaluate complex healthcare interventions. PMID:21219620

Evaluation of a large scale implementation of disease management programmes in various Dutch regions: a study protocol.

PubMed

Lemmens, Karin M M; Rutten-Van Mölken, Maureen P M H; Cramm, Jane M; Huijsman, Robbert; Bal, Roland A; Nieboer, Anna P

2011-01-10

Disease management programmes (DMPs) have been developed to improve effectiveness and economic efficiency within chronic care delivery by combining patient-related, professional-directed, and organisational interventions. The benefits of DMPs within different settings, patient groups, and versions remain unclear. In this article we propose a protocol to evaluate a range of current DMPs by capturing them in a single conceptual framework, employing comparable structure, process, and outcome measures, and combining qualitative and quantitative research methods. To assess DMP effectiveness a practical clinical trial will be conducted. Twenty-two disease management experiments will be studied in various Dutch regions consisting of a variety of collaborations between organisations and/or professionals. Patient cohorts include those with cardiovascular diseases, chronic obstructive pulmonary disease, diabetes, stroke, depression, psychotic diseases, and eating disorders. Our methodological approach combines qualitative and quantitative research methods to enable a comprehensive evaluation of complex programmes. Process indicators will be collected from health care providers' data registries and measured via physician and staff questionnaires. Patient questionnaires include health care experiences, health care utilisation, and quality of life. Qualitative data will be gathered by means of interviews and document analysis for an in depth description of project interventions and the contexts in which DMPs are embedded, and an ethnographic process evaluation in five DMPs. Such a design will provide insight into ongoing DMPs and demonstrate which elements of the intervention are potentially (cost)-effective for which patient populations. It will also enable sound comparison of the results of the different programmes. The study will lead to a better understanding of (1) the mechanisms of disease management, (2) the feasibility, and cost-effectiveness of a disease management approach to improving health care, and (3) the factors that determine success and failure of DMPs. Our study results will be relevant to decision makers and managers who confront the challenge of implementing and integrating DMPs into the health care system. Moreover, it will contribute to the search for methods to evaluate complex healthcare interventions.

Collagenous mucosal inflammatory diseases of the gastrointestinal tract.

PubMed

Freeman, Hugh J

2005-07-01

Collagenous mucosal inflammatory diseases involve the columnar-lined gastric and intestinal mucosa and have become recognized increasingly as a significant cause of symptomatic morbidity, particularly in middle-aged and elderly women, especially with watery diarrhea. Still, mechanisms involved in the pathogenesis of this diarrhea remain poorly understood and require further elucidation. The prognosis and long-term outcome of these disorders has been documented only to a limited extent. Recent clinical and pathologic studies have indicated that collagenous mucosal inflammatory disease is a more extensive pathologic process that concomitantly may involve several sites in the gastric and intestinal mucosa. The dominant pathologic lesion is a distinct subepithelial hyaline-like deposit that has histochemical and ultrastructural features of collagen overlying a microscopically defined inflammatory process. An intimate relationship with other autoimmune connective tissue disorders is evident, particularly celiac disease. This is intriguing because these collagenous disorders have not been shown to be gluten dependent. Collagenous mucosal inflammatory disorders may represent a relatively unique but generalized inflammatory response to a multitude of causes, including celiac disease, along with a diverse group of pharmacologic agents. Some recent reports have documented treatment success but histopathologic reversal has been more difficult to substantiate owing to the focal, sometimes extensive nature, of this pathologic process.

Classic and new animal models of Parkinson's disease.

PubMed

Blesa, Javier; Phani, Sudarshan; Jackson-Lewis, Vernice; Przedborski, Serge

2012-01-01

Neurological disorders can be modeled in animals so as to recreate specific pathogenic events and behavioral outcomes. Parkinson's Disease (PD) is the second most common neurodegenerative disease of an aging population, and although there have been several significant findings about the PD disease process, much of this process still remains a mystery. Breakthroughs in the last two decades using animal models have offered insights into the understanding of the PD disease process, its etiology, pathology, and molecular mechanisms. Furthermore, while cellular models have helped to identify specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are useful for testing new neuroprotective or neurorestorative strategies. Moreover, significant advances in the modeling of additional PD features have come to light in both classic and newer models. In this review, we try to provide an updated summary of the main characteristics of these models as well as the strengths and weaknesses of what we believe to be the most popular PD animal models. These models include those produced by 6-hydroxydopamine (6-OHDA), 1-methyl-1,2,3,6-tetrahydropiridine (MPTP), rotenone, and paraquat, as well as several genetic models like those related to alpha-synuclein, PINK1, Parkin and LRRK2 alterations.

Endothelium and Its Alterations in Cardiovascular Diseases: Life Style Intervention

PubMed Central

Paganelli, Corrado; Buffoli, Barbara; Rodella, Luigi Fabrizio; Rezzani, Rita

2014-01-01

The endothelium, which forms the inner cellular lining of blood vessels and lymphatics, is a highly metabolically active organ that is involved in many physiopathological processes, including the control of vasomotor tone, barrier function, leukocyte adhesion, and trafficking and inflammation. In this review, we summarized and described the following: (i) endothelial cell function in physiological conditions and (ii) endothelial cell activation and dysfunction in the main cardiovascular diseases (such as atherosclerosis, and hypertension) and to diabetes, cigarette smoking, and aging physiological process. Finally, we presented the currently available evidence that supports the beneficial effects of physical activity and various dietary compounds on endothelial functions. PMID:24719887

Riga-Fede-like disease in an AIDS patient.

PubMed

Cunha, Vanessa Santos; Rocha Zanol, Jorge David; Sprinz, Eduardo

2007-12-01

Riga-Fede disease is a benign and ulcerative process that occurs as a result of repetitive trauma of the oral mucosal surfaces by the teeth. The authors describe here a case of a 40-year-old man in rescue therapy for advanced AIDS with a 2-month history of an ulcerated area on the dorsal surface of his tongue, which was histopathologically consistent with Riga-Fede disease. This case report is unique because it is the first time that this lesion has been reported in an AIDS patient, and Riga-Fede disease should be included in the differential diagnosis of a tongue ulcer in these populations.

Wilms' tumour 1 (WT1) in development, homeostasis and disease.

PubMed

Hastie, Nicholas D

2017-08-15

The study of genes mutated in human disease often leads to new insights into biology as well as disease mechanisms. One such gene is Wilms' tumour 1 ( WT1 ), which plays multiple roles in development, tissue homeostasis and disease. In this Primer, I summarise how this multifaceted gene functions in various mammalian tissues and organs, including the kidney, gonads, heart and nervous system. This is followed by a discussion of our current understanding of the molecular mechanisms by which WT1 and its two major isoforms regulate these processes at the transcriptional and post-transcriptional levels. © 2017. Published by The Company of Biologists Ltd.

Proteomic Profiling of Cranial (Superior) Cervical Ganglia Reveals Beta-Amyloid and Ubiquitin Proteasome System Perturbations in an Equine Multiple System Neuropathy.

PubMed

McGorum, Bruce C; Pirie, R Scott; Eaton, Samantha L; Keen, John A; Cumyn, Elizabeth M; Arnott, Danielle M; Chen, Wenzhang; Lamont, Douglas J; Graham, Laura C; Llavero Hurtado, Maica; Pemberton, Alan; Wishart, Thomas M

2015-11-01

Equine grass sickness (EGS) is an acute, predominantly fatal, multiple system neuropathy of grazing horses with reported incidence rates of ∼2%. An apparently identical disease occurs in multiple species, including but not limited to cats, dogs, and rabbits. Although the precise etiology remains unclear, ultrastructural findings have suggested that the primary lesion lies in the glycoprotein biosynthetic pathway of specific neuronal populations. The goal of this study was therefore to identify the molecular processes underpinning neurodegeneration in EGS. Here, we use a bottom-up approach beginning with the application of modern proteomic tools to the analysis of cranial (superior) cervical ganglion (CCG, a consistently affected tissue) from EGS-affected patients and appropriate control cases postmortem. In what appears to be the proteomic application of modern proteomic tools to equine neuronal tissues and/or to an inherent neurodegenerative disease of large animals (not a model of human disease), we identified 2,311 proteins in CCG extracts, with 320 proteins increased and 186 decreased by greater than 20% relative to controls. Further examination of selected proteomic candidates by quantitative fluorescent Western blotting (QFWB) and subcellular expression profiling by immunohistochemistry highlighted a previously unreported dysregulation in proteins commonly associated with protein misfolding/aggregation responses seen in a myriad of human neurodegenerative conditions, including but not limited to amyloid precursor protein (APP), microtubule associated protein (Tau), and multiple components of the ubiquitin proteasome system (UPS). Differentially expressed proteins eligible for in silico pathway analysis clustered predominantly into the following biofunctions: (1) diseases and disorders, including; neurological disease and skeletal and muscular disorders and (2) molecular and cellular functions, including cellular assembly and organization, cell-to-cell signaling and interaction (including epinephrine, dopamine, and adrenergic signaling and receptor function), and small molecule biochemistry. Interestingly, while the biofunctions identified in this study may represent pathways underpinning EGS-induced neurodegeneration, this is also the first demonstration of potential molecular conservation (including previously unreported dysregulation of the UPS and APP) spanning the degenerative cascades from an apparently unrelated condition of large animals, to small animal models with altered neuronal vulnerability, and human neurological conditions. Importantly, this study highlights the feasibility and benefits of applying modern proteomic techniques to veterinary investigations of neurodegenerative processes in diseases of large animals. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Climate Change and the Neglected Tropical Diseases.

PubMed

Booth, Mark

2018-01-01

Climate change is expected to impact across every domain of society, including health. The majority of the world's population is susceptible to pathological, infectious disease whose life cycles are sensitive to environmental factors across different physical phases including air, water and soil. Nearly all so-called neglected tropical diseases (NTDs) fall into this category, meaning that future geographic patterns of transmission of dozens of infections are likely to be affected by climate change over the short (seasonal), medium (annual) and long (decadal) term. This review offers an introduction into the terms and processes deployed in modelling climate change and reviews the state of the art in terms of research into how climate change may affect future transmission of NTDs. The 34 infections included in this chapter are drawn from the WHO NTD list and the WHO blueprint list of priority diseases. For the majority of infections, some evidence is available of which environmental factors contribute to the population biology of parasites, vectors and zoonotic hosts. There is a general paucity of published research on the potential effects of decadal climate change, with some exceptions, mainly in vector-borne diseases. © 2018 Elsevier Ltd All rights reserved.

Comparative Effectiveness Research in Lung Diseases and Sleep Disorders

PubMed Central

Lieu, Tracy A.; Au, David; Krishnan, Jerry A.; Moss, Marc; Selker, Harry; Harabin, Andrea; Connors, Alfred

2011-01-01

The Division of Lung Diseases of the National Heart, Lung, and Blood Institute (NHLBI) held a workshop to develop recommendations on topics, methodologies, and resources for comparative effectiveness research (CER) that will guide clinical decision making about available treatment options for lung diseases and sleep disorders. A multidisciplinary group of experts with experience in efficacy, effectiveness, implementation, and economic research identified (a) what types of studies the domain of CER in lung diseases and sleep disorders should include, (b) the criteria and process for setting priorities, and (c) current resources for and barriers to CER in lung diseases. Key recommendations were to (1) increase efforts to engage stakeholders in developing CER questions and study designs; (2) invest in further development of databases and other infrastructure, including efficient methods for data sharing; (3) make full use of a broad range of study designs; (4) increase the appropriate use of observational designs and the support of methodologic research; (5) ensure that committees that review CER grant applications include persons with appropriate perspective and expertise; and (6) further develop the workforce for CER by supporting training opportunities that focus on the methodologic and practical skills needed. PMID:21965016

Alzheimer’s Disease Neuroimaging Initiative biomarkers as quantitative phenotypes: Genetics core aims, progress, and plans

PubMed Central

Saykin, Andrew J.; Shen, Li; Foroud, Tatiana M.; Potkin, Steven G.; Swaminathan, Shanker; Kim, Sungeun; Risacher, Shannon L.; Nho, Kwangsik; Huentelman, Matthew J.; Craig, David W.; Thompson, Paul M.; Stein, Jason L.; Moore, Jason H.; Farrer, Lindsay A.; Green, Robert C.; Bertram, Lars; Jack, Clifford R.; Weiner, Michael W.

2010-01-01

The role of the Alzheimer’s Disease Neuroimaging Initiative Genetics Core is to facilitate the investigation of genetic influences on disease onset and trajectory as reflected in structural, functional, and molecular imaging changes; fluid biomarkers; and cognitive status. Major goals include (1) blood sample processing, genotyping, and dissemination, (2) genome-wide association studies (GWAS) of longitudinal phenotypic data, and (3) providing a central resource, point of contact and planning group for genetics within Alzheimer’s Disease Neuroimaging Initiative. Genome-wide array data have been publicly released and updated, and several neuroimaging GWAS have recently been reported examining baseline magnetic resonance imaging measures as quantitative phenotypes. Other preliminary investigations include copy number variation in mild cognitive impairment and Alzheimer’s disease and GWAS of baseline cerebrospinal fluid biomarkers and longitudinal changes on magnetic resonance imaging. Blood collection for RNA studies is a new direction. Genetic studies of longitudinal phenotypes hold promise for elucidating disease mechanisms and risk, development of therapeutic strategies, and refining selection criteria for clinical trials. PMID:20451875

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

PubMed Central

Barnett, Timothy C.; McArthur, Jason D.; Cole, Jason N.; Gillen, Christine M.; Henningham, Anna; Sriprakash, K. S.; Sanderson-Smith, Martina L.; Nizet, Victor

2014-01-01

SUMMARY Streptococcus pyogenes, also known as group A Streptococcus (GAS), causes mild human infections such as pharyngitis and impetigo and serious infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. Furthermore, repeated GAS infections may trigger autoimmune diseases, including acute poststreptococcal glomerulonephritis, acute rheumatic fever, and rheumatic heart disease. Combined, these diseases account for over half a million deaths per year globally. Genomic and molecular analyses have now characterized a large number of GAS virulence determinants, many of which exhibit overlap and redundancy in the processes of adhesion and colonization, innate immune resistance, and the capacity to facilitate tissue barrier degradation and spread within the human host. This improved understanding of the contribution of individual virulence determinants to the disease process has led to the formulation of models of GAS disease progression, which may lead to better treatment and intervention strategies. While GAS remains sensitive to all penicillins and cephalosporins, rising resistance to other antibiotics used in disease treatment is an increasing worldwide concern. Several GAS vaccine formulations that elicit protective immunity in animal models have shown promise in nonhuman primate and early-stage human trials. The development of a safe and efficacious commercial human vaccine for the prophylaxis of GAS disease remains a high priority. PMID:24696436

Reviews.

ERIC Educational Resources Information Center

Repak, Arthur J.; And Others

1988-01-01

Computer software, audiovisuals, and books are reviewed. Includes topics on interfacing, ionic equilibrium, space, the classification system, Acquired Immune Disease Syndrome, evolution, human body processes, energy, pesticides, teaching school, cells, and geological aspects. Availability, price, and a description of each are provided. (RT)

Phytometric intelligence sensors

NASA Technical Reports Server (NTRS)

Seelig, Hans-Dieter (Inventor); Stoner, II, Richard J. (Inventor); Hoehn, Alexander (Inventor); Adams, III, William Walter (Inventor)

2010-01-01

Methods and apparatus for determining when plants require watering, and methods of attending to the watering of plants including signaling the grower that the plants are in need of hydration are provided. The novel methods include real-time measurement of plant metabolics and phytometric physiology changes of intrinsic physical or behavioral traits within the plant such as determining physiological flux measurement of enzyme flux due to environmental changes such as the wind and drought stress, soil and plant mineral deficiencies, or the interaction with a bio-control for organic disease control including, cell movement, signal transduction, internal chemical processes and external environmental processes including when plants require watering, and methods of attending to the watering of plants including signaling the grower that the plants are in need of hydration.

B cell biology: implications for treatment of systemic lupus erythematosus.

PubMed

Anolik, J H

2013-04-01

B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody-independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B cell activation thresholds, B cell longevity, and apoptotic cell processing. Once tolerance is broken, autoantibodies contribute to autoimmunity by multiple mechanisms including immune-complex mediated Type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread utilization of B cell depletion therapy in autoimmune diseases and the need for new therapeutic approaches in SLE, a better understanding of human B cell subsets and the balance of pathogenic and regulatory functions is of the essence.

Validity of juvenile idiopathic arthritis diagnoses using administrative health data.

PubMed

Stringer, Elizabeth; Bernatsky, Sasha

2015-03-01

Administrative health databases are valuable sources of data for conducting research including disease surveillance, outcomes research, and processes of health care at the population level. There has been limited use of administrative data to conduct studies of pediatric rheumatic conditions and no studies validating case definitions in Canada. We report a validation study of incident cases of juvenile idiopathic arthritis in the Canadian province of Nova Scotia. Cases identified through administrative data algorithms were compared to diagnoses in a clinical database. The sensitivity of algorithms that included pediatric rheumatology specialist claims was 81-86%. However, 35-48% of cases that were identified could not be verified in the clinical database depending on the algorithm used. Our case definitions would likely lead to overestimates of disease burden. Our findings may be related to issues pertaining to the non-fee-for-service remuneration model in Nova Scotia, in particular, systematic issues related to the process of submitting claims.

Social Support and Heart Failure: Differing Effects by Race

DTIC Science & Technology

2015-05-11

responses. These compensatory physiologic responses include increased sympathetic nervous system activity, inflammation, and constriction of blood vessels... physiological differences between African Americans and Caucasians. For instance the process by which sodium is processed in the body may vary between...associated cardiovascular and inflammatory diseases (76). One important hormone at work in the cardiovascular system is aldosterone and it may have a

Formation and Degradation of Beta-casomorphins in Dairy Processing.

PubMed

Nguyen, Duc Doan; Johnson, Stuart Keith; Busetti, Francesco; Solah, Vicky Ann

2015-01-01

Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from β-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B β-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme-linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown.

The impacts of livestock diseases and their control on growth and development processes that are pro-poor

PubMed Central

Perry, Brian; Grace, Delia

2009-01-01

Poverty is now at the heart of development discourse; we discuss how it is measured and understood. We next consider the negative and positive impacts of livestock on pro-poor development. Taking a value-chain approach that includes keepers, users and eaters of livestock, we identify diseases that are road blocks on the ‘three livestock pathways out of poverty’. We discuss livestock impacts on poverty reduction and review attempts to prioritize the livestock diseases relevant to the poor. We make suggestions for metrics that better measure disease impact and show the benefits of more rigorous evaluation before reviewing recent attempts to measure the importance of disease to the poor. High impact of a disease does not guarantee high benefits from its control; other factors must be taken into consideration, including technical feasibility and political desirability. We conclude by considering how we might better understand and exploit the roles of livestock and improved animal health by posing three speculative questions on the impact of livestock diseases and their control on global poverty: how can understanding livestock and poverty links help disease control?; if global poverty reduction was the aim of livestock disease control, how would it differ from the current model?; and how much of the impact of livestock disease on poverty is due to disease control policy rather than disease itself? PMID:19687035

Improving Chronic Diseases Management Through the Development of an Evidence-Based Resource.

PubMed

Khalil, Hanan; Chambers, Helen; Munn, Zachary; Porritt, Kylie

2015-06-01

There is a large gap between evidence and practice within health care, particularly within the field of chronic disease. To reduce this gap and improve the management of chronic disease, a collaborative partnership between two schools within a large university and two industry partners (a large regional rural hospital and a rural community health center) in rural Victoria, Australia, was developed. The aim of the collaboration was to promote the development of translation science and the implementation of evidence-based health care in chronic disease with a specific focus on developing evidence-based resources that are easily accessed by clinicians. A working group consisting of members of the collaborating organizations and an internationally renowned expert reference group was formed. The group acted as a steering committee and was tasked with developing a taxonomy of the resources. In addition, a peer review process of all resources was established. A corresponding reference group consisting of researchers and clinicians who are clinical experts in various fields was involved in the review process. The resources developed by the group include evidence summaries and recommended practices made available on a web-based database, which can be accessed via subscription by clinicians and researchers worldwide. As of mid-2014, there were 109 new evidence summaries and 25 recommended practices detailing the best available evidence on topics related to chronic disease management including asthma, diabetes, heart failure, dementia, and others. Training sessions and a newsletter were developed for clinicians within the node to enable them to use the content effectively. This paper describes the processes involved in the successful development of the collaborative partnership and its evolution into producing a valuable resource for the translation of evidence into practice in the areas of chronic disease management. The resource developed is being used by clinicians to inform practice and support their clinical decision making. © 2015 Sigma Theta Tau International.

Cerebral correlates of psychotic syndromes in neurodegenerative diseases.

PubMed

Jellinger, Kurt A

2012-05-01

Psychosis has been recognized as a common feature in neurodegenerative diseases and a core feature of dementia that worsens most clinical courses. It includes hallucinations, delusions including paranoia, aggressive behaviour, apathy and other psychotic phenomena that occur in a wide range of degenerative disorders including Alzheimer's disease, synucleinopathies (Parkinson's disease, dementia with Lewy bodies), Huntington's disease, frontotemporal degenerations, motoneuron and prion diseases. Many of these psychiatric manifestations may be early expressions of cognitive impairment, but often there is a dissociation between psychotic/behavioural symptoms and the rather linear decline in cognitive function, suggesting independent pathophysiological mechanisms. Strictly neuropathological explanations are likely to be insufficient to explain them, and a large group of heterogeneous factors (environmental, neurochemical changes, genetic factors, etc.) may influence their pathogenesis. Clinico-pathological evaluation of behavioural and psychotic symptoms (PS) in the setting of neurodegenerative and dementing disorders presents a significant challenge for modern neurosciences. Recognition and understanding of these manifestations may lead to the development of more effective preventive and therapeutic options that can serve to delay long-term progression of these devastating disorders and improve the patients' quality of life. A better understanding of the pathophysiology and distinctive pathological features underlying the development of PS in neurodegenerative diseases may provide important insights into psychotic processes in general. © 2011 The Author Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Current perspectives in transfusion-transmitted infectious diseases: emerging and re-emerging infections.

PubMed

Stramer, S L

2014-07-01

In August 2009, a group from the AABB (Stramer et al., Transfusion 2009;99:1S-29S, Emerging Infectious Disease Agents and their Potential Threat to Transfusion Safety; http://www.aabb.org/resources/bct/eid/Pages/default.aspx) published a Supplement to Transfusion that reviewed emerging infectious disease (EID) agents that pose a real or theoretical threat to transfusion safety, but for which an existing effective intervention is lacking. The necessary attributes for transfusion transmission were outlined including: presence of the agent in blood during the donor's asymptomatic phase, the agent's survival/persistence in blood during processing/storage, and lastly that the agent must be recognized as responsible for a clinically apparent outcome in at least a proportion of recipients who become infected. Without these attributes, agents are not considered as a transfusion-transmission threat and were excluded. Sixty-eight such agents were identified with enough evidence/likelihood of transfusion transmission (e.g., blood phase) and potential for clinical disease to warrant further consideration. In the Supplement, Fact Sheets (FS) were published providing information on: agent classification; disease agent's importance; clinical syndromes/diseases caused; transmission modes (including vectors/reservoirs); likelihood of transfusion transmission, and if proven to be transfusion-transmitted, information on known cases; the feasibility/predicted success of interventions for donor screening (questioning) and tests available for diagnostics/ adapted for donor screening; and finally, the efficacy, if known, of inactivation methods for plasma-derived products. The Supplement included a separate section on pathogen reduction using published data. Agents were prioritized relative to their scientific/epidemiologic threat and their perceived threat to the community including concerns expressed by the regulators of blood. Agents given the highest priority due to a known transfusion-transmission threat and severe/fatal disease in recipients were the vCJD prion, dengue viruses and the obligate red-cell parasite that causes babesiosis ( B. microti and related Babesia ). Although the focus of the Supplement was towards the United States and Canada, many of the agents (and the process) are applicable worldwide. Since the publication of the Supplement, six new FSs (yellow fever viruses-including vaccine breakthrough infections, miscellaneous arboviruses, XMRV, human parvoviruses/bocaviruses other than B19, and most recently the Middle East respiratory syndrome coronavirus, MERS-CoV) were added and 14 existing FSs updated (Anaplasma, Babesia, Bartonella, Erhlichia, chronic wasting disease-CWD, human prions other than vCJD, vCJD, Coxiella burnetii -the agent of Q fever, dengue viruses, HAV, HEV, Japanese encephalitis-JE complex, tick-borne encephalitis viruses-TBEV, and human parvovirus B19). Also, tables were released outlining pathogen reduction clinical trials/results (published) and availability/commercial routine use of such technologies by country. Of necessity, the list of EID agents is not, and can never be, complete due to the nature of emergence. We recognized that a system of assessing the risk/threat of EIDs for their potential impact on blood safety and availability must include processes for monitoring, identifying, evaluating, estimating severity, assessing risk and developing interventions. Thus, a 'toolkit' containing the necessary 'tools' from EID monitoring (horizon scanning) to validation/effectiveness evaluations of interventions is being developed. The goal is, to develop a systematic approach to risk assessment and intervention development for the impact of emerging infectious upon blood safety intended to educate and provide advise about risks/interventions in a timely/accurate fashion. The process and final product (toolkit) including methods to monitor EID agent emergence, identification/recognition of a transfusion-transmission threat, methods for quantitative risk assessments, and the appropriate management of such threats should be considered for implementation by all blood systems.

Conceptual-driven classification for coding advise in health insurance reimbursement.

PubMed

Li, Sheng-Tun; Chen, Chih-Chuan; Huang, Fernando

2011-01-01

With the non-stop increases in medical treatment fees, the economic survival of a hospital in Taiwan relies on the reimbursements received from the Bureau of National Health Insurance, which in turn depend on the accuracy and completeness of the content of the discharge summaries as well as the correctness of their International Classification of Diseases (ICD) codes. The purpose of this research is to enforce the entire disease classification framework by supporting disease classification specialists in the coding process. This study developed an ICD code advisory system (ICD-AS) that performed knowledge discovery from discharge summaries and suggested ICD codes. Natural language processing and information retrieval techniques based on Zipf's Law were applied to process the content of discharge summaries, and fuzzy formal concept analysis was used to analyze and represent the relationships between the medical terms identified by MeSH. In addition, a certainty factor used as reference during the coding process was calculated to account for uncertainty and strengthen the credibility of the outcome. Two sets of 360 and 2579 textual discharge summaries of patients suffering from cerebrovascular disease was processed to build up ICD-AS and to evaluate the prediction performance. A number of experiments were conducted to investigate the impact of system parameters on accuracy and compare the proposed model to traditional classification techniques including linear-kernel support vector machines. The comparison results showed that the proposed system achieves the better overall performance in terms of several measures. In addition, some useful implication rules were obtained, which improve comprehension of the field of cerebrovascular disease and give insights to the relationships between relevant medical terms. Our system contributes valuable guidance to disease classification specialists in the process of coding discharge summaries, which consequently brings benefits in aspects of patient, hospital, and healthcare system. Copyright © 2010 Elsevier B.V. All rights reserved.

Complex Relationships Between Food, Diet and the Microbiome

PubMed Central

Pace, Laura A.; Crowe, Sheila E.

2018-01-01

Diet is a risk factor in a number of medically important disease states including obesity, celiac disease and functional gastrointestinal disorders. Modification of diet can prevent, treat or alleviate some of the symptoms associated with these diseases and improve general health. It is important to provide patients with simple dietary recommendations in order to increase the probability of successful implementation. These include increasing vegetable, fruit and fiber intake, consuming lean protein sources to enhance satiety, avoiding or severely limiting highly processed foods, and reducing portion sizes for overweight and obese patients. Women can play an important role in maintaining family health by making more informed dietary decisions. The gut microbiome may play a role in some gastrointestinal disorders. However better designed studies are required to differentiate correlation from causation in this emerging area. PMID:27261897

Towards first principle medical diagnostics: on the importance of disease-disease and sign-sign interactions

NASA Astrophysics Data System (ADS)

Ramezanpour, Abolfazl; Mashaghi, Alireza

2017-07-01

A fundamental problem in medicine and biology is to assign states, e.g. healthy or diseased, to cells, organs or individuals. State assignment or making a diagnosis is often a nontrivial and challenging process and, with the advent of omics technologies, the diagnostic challenge is becoming more and more serious. The challenge lies not only in the increasing number of measured properties and dynamics of the system (e.g. cell or human body) but also in the co-evolution of multiple states and overlapping properties, and degeneracy of states. We develop, from first principles, a generic rational framework for state assignment in cell biology and medicine, and demonstrate its applicability with a few simple theoretical case studies from medical diagnostics. We show how disease-related statistical information can be used to build a comprehensive model that includes the relevant dependencies between clinical and laboratory findings (signs) and diseases. In particular, we include disease-disease and sign-sign interactions and study how one can infer the probability of a disease in a patient with given signs. We perform comparative analysis with simple benchmark models to check the performances of our models. We find that including interactions can significantly change the statistical importance of the signs and diseases. This first principles approach, as we show, facilitates the early diagnosis of disease by taking interactions into accounts, and enables the construction of consensus diagnostic flow charts. Additionally, we envision that our approach will find applications in systems biology, and in particular, in characterizing the phenome via the metabolome, the proteome, the transcriptome, and the genome.

Chronic Kidney Disease and Sleeping Disordered Breathing (SDB).

PubMed

Santos, Roberto Sávio Silva; Motwani, Shveta S; Elias, Rosilene Motta

2016-01-01

The outlines of the current manuscript are: 1. Re-establish the link between hypertension and SDB including prevalence, mechanism, and reversal of process (i.e. improvement in hypertension with improvement in SDB), why it is important-cardiovascular mortality with numbers. 2. Re-establish the link between hypertension and CKD including same points as above. Then ask if both CKD and SDB are combined, what happens to hypertension and cardiovascular mortality. 3. Lastly, talk about links between CKD and SDB on how each process feeds on the other and is a growing, common problem.

Three-Dimensional Coculture Of Human Small-Intestine Cells

NASA Technical Reports Server (NTRS)

Wolf, David; Spaulding, Glen; Goodwin, Thomas J.; Prewett, Tracy

1994-01-01

Complex three-dimensional masses of normal human epithelial and mesenchymal small-intestine cells cocultured in process involving specially designed bioreactors. Useful as tissued models for studies of growth, regulatory, and differentiation processes in normal intestinal tissues; diseases of small intestine; and interactions between cells of small intestine and viruses causing disease both in small intestine and elsewhere in body. Process used to produce other tissue models, leading to advances in understanding of growth and differentiation in developing organisms, of renewal of tissue, and of treatment of myriad of clinical conditions. Prior articles describing design and use of rotating-wall culture vessels include "Growing And Assembling Cells Into Tissues" (MSC-21559), "High-Aspect-Ratio Rotating Cell-Culture Vessel" (MSC-21662), and "In Vitro, Matrix-Free Formation Of Solid Tumor Spheroids" (MSC-21843).

Long non-coding RNAs involved in autophagy regulation

PubMed Central

Yang, Lixian; Wang, Hanying; Shen, Qi; Feng, Lifeng; Jin, Hongchuan

2017-01-01

Autophagy degrades non-functioning or damaged proteins and organelles to maintain cellular homeostasis in a physiological or pathological context. Autophagy can be protective or detrimental, depending on its activation status and other conditions. Therefore, autophagy has a crucial role in a myriad of pathophysiological processes. From the perspective of autophagy-related (ATG) genes, the molecular dissection of autophagy process and the regulation of its level have been largely unraveled. However, the discovery of long non-coding RNAs (lncRNAs) provides a new paradigm of gene regulation in almost all important biological processes, including autophagy. In this review, we highlight recent advances in autophagy-associated lncRNAs and their specific autophagic targets, as well as their relevance to human diseases such as cancer, cardiovascular disease, diabetes and cerebral ischemic stroke. PMID:28981093

Complex and differential glial responses in Alzheimer's disease and ageing.

PubMed

Rodríguez, José J; Butt, Arthur M; Gardenal, Emanuela; Parpura, Vladimir; Verkhratsky, Alexei

2016-01-01

Glial cells and their association with neurones are fundamental for brain function. The emergence of complex neurone-glial networks assures rapid information transfer, creating a sophisticated circuitry where both types of neural cells work in concert, serving different activities. All glial cells, represented by astrocytes, oligodendrocytes, microglia and NG2-glia, are essential for brain homeostasis and defence. Thus, glia are key not only for normal central nervous system (CNS) function, but also to its dysfunction, being directly associated with all forms of neuropathological processes. Therefore, the progression and outcome of neurological and neurodegenerative diseases depend on glial reactions. In this review, we provide a concise account of recent data obtained from both human material and animal models demonstrating the pathological involvement of glia in neurodegenerative processes, including Alzheimer's disease (AD), as well as physiological ageing.

US FDA review and regulation of preventive vaccines for infectious disease indications: impact of the FDA Amendments Act 2007.

PubMed

Gruber, Marion F

2011-07-01

Vaccines for prevention or treatment of infectious diseases are biological products that are regulated by the Office of Vaccines Research and Review in the Center for Biologics Evaluation and Research of the US FDA. The legal framework for the regulation of vaccines derives primarily from Section 351 of the Public Health Service Act and from certain sections of the Federal Food, Drug and Cosmetic Act (FFD & C Act). The FDA Amendments Act of 2007 (FDAAA 2007) includes extensive modifications to the FFD & C Act. This article provides an overview of the review process for preventive vaccines and highlights applicable statutory provisions. In addition, this article will discuss changes in the pre-and post-licensure evaluation process for preventive and therapeutic infectious disease vaccines since implementation of the FDAAA 2007.

[Rheumatoid arthritis as a connective tissue disease].

PubMed

Targońska-Stępniak, Bożena

2018-01-01

The available data indicate that seropositive rheumatoid arthritis (RA) develops as a result of systemic, autoimmune reaction directed against a range of "self" peptides/proteins that have undergone specific forms of post-translational modification. The development and progress of autoimmunity may be triggered by non-specific, local inflammatory processes outside the joints, for example in the oral or respiratory mucous membrane. The disease occurs in genetically susceptible individuals under the influence of environmental risk factors that promote autoimmunity and consequently the inflammatory process. Smoking is particularly linked with RA pathogenesis. Synovitis of multiple, symmetrical, peripheral joints is the most typical feature of RA which results in irreversible damage to joints structure and as a consequence in disability of patients. However, the inflammatory process in the course of RA has a systemic, constitutional nature. Therefore, extra-articular symptoms with internal organ involvement may occur additionally to synovitis, what is an unfavorable prognostic factor. Extra-articular manifestations of RA are associated with the high disease activity both inflammatory and immunological. They occur in patients with severe form of the disease and contribute to a significant lifespan reduction. This is usually associated with progressive atherosclerosis and cardiovascular complications. The systemic inhibition of an abnormal immune system activity is the mainstay of the effective RA treatment. The currently used disease modifying antirheumatic drugs affect the activity and function of different constituents of the immune system, including B and T lymphocytes and the main pro-inflammatory cytokines, and contribute to autoimmune and inflammatory processes.

Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases

PubMed Central

Lundmark, Anna; Davanian, Haleh; Båge, Tove; Johannsen, Gunnar; Koro, Catalin; Lundeberg, Joakim; Yucel-Lindberg, Tülay

2015-01-01

The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID:26686060

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study

PubMed Central

Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A.; Austin, John H. M.; Bluemke, David A.; Carr, James; Choi, Jiwoong; Goldstein, Thomas A.; Gomes, Antoinette S.; Hoffman, Eric A.; Kawut, Steven M.; Lima, Joao; Michos, Erin D.; Post, Wendy S.; Po, Ming Jack; Prince, Martin R.; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M.; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M.

2015-01-01

Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature. PMID:26067761

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

PubMed

Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A; Austin, John H M; Bluemke, David A; Carr, James; Choi, Jiwoong; Goldstein, Thomas A; Gomes, Antoinette S; Hoffman, Eric A; Kawut, Steven M; Lima, Joao; Michos, Erin D; Post, Wendy S; Po, Ming Jack; Prince, Martin R; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M; Barr, R Graham

2015-09-01

Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

Pre-pregnancy counselling for women with chronic kidney disease: a retrospective analysis of nine years' experience.

PubMed

Wiles, Kate S; Bramham, Kate; Vais, Alina; Harding, Kate R; Chowdhury, Paramit; Taylor, Cath J; Nelson-Piercy, Catherine

2015-03-14

Women with chronic kidney disease have an increased risk of maternal and fetal complications in pregnancy. Pre-pregnancy counselling is recommended but the format of the counselling process and the experience of the patient have never been assessed. This study examines the experience of women with chronic kidney disease attending pre-pregnancy counselling and evaluates their pregnancy outcomes. This is a cross-sectional assessment of 179 women with chronic kidney disease attending a pre-pregnancy counselling clinic (2003-2011) with retrospective evaluation of aetiology, comorbidity, treatment and adverse pregnancy outcome compared with 277 hospital controls. It includes an analysis of descriptive data and free text content from 72 questionnaire responders. 65/72 (90%) of women found the clinic informative. 66 women (92%) felt that the consultation had helped them decide about pursuing pregnancy. 12 women (17%) found the multidisciplinary process intimidating. Free text comments supported the positive nature of the counselling experience, but also highlighted issues of access and emotional impact. Adverse pregnancy outcome rates were significantly higher in women with chronic kidney disease: 7/35 (20%) had pre-eclampsia (p < 0.001), 8/35 (23%) infants were small for gestational age (p < 0.001), 11/35 (31%) had preterm deliveries (<37 weeks) (p < 0.001) and 5/35 (14%) had a pregnancy loss compared with 4%, 10%, 8% and 3% of controls respectively. Women with a diverse range of renal disease severity and complexity attend pre-pregnancy counselling. Factors affecting pregnancy include hypertension, proteinuria and teratogenic medication. It is important to be able to inform women of the risks to them and their babies before pregnancy in order to facilitate informed-decision making. Most women with chronic kidney disease attending a pre-pregnancy counselling clinic report a positive experience.

MR imaging of the pelvis: a guide to incidental musculoskeletal findings for abdominal radiologists.

PubMed

Gaetke-Udager, Kara; Girish, Gandikota; Kaza, Ravi K; Jacobson, Jon; Fessell, David; Morag, Yoav; Jamadar, David

2014-08-01

Occasionally patients who undergo magnetic resonance imaging for presumed pelvic disease demonstrate unexpected musculoskeletal imaging findings in the imaged field. Such incidental findings can be challenging to the abdominal radiologist, who may not be familiar with their appearance or know the appropriate diagnostic considerations. Findings can include both normal and abnormal bone marrow, osseous abnormalities such as Paget's disease, avascular necrosis, osteomyelitis, stress and insufficiency fractures, and athletic pubalgia, benign neoplasms such as enchondroma and bone island, malignant processes such as metastasis and chondrosarcoma, soft tissue processes such as abscess, nerve-related tumors, and chordoma, joint- and bursal-related processes such as sacroiliitis, iliopsoas bursitis, greater trochanteric pain syndrome, and labral tears, and iatrogenic processes such as bone graft or bone biopsy. Though not all-encompassing, this essay will help abdominal radiologists to identify and describe this variety of pelvic musculoskeletal conditions, understand key radiologic findings, and synthesize a differential diagnosis when appropriate.

Coordinating Regulation of Gene Expression in Cardiovascular Disease: Interactions between Chromatin Modifiers and Transcription Factors

PubMed Central

Bauer, Ashley J.; Martin, Kathleen A.

2017-01-01

Cardiovascular disease is a leading cause of death with increasing economic burden. The pathogenesis of cardiovascular diseases is complex, but can arise from genetic and/or environmental risk factors. This can lead to dysregulated gene expression in numerous cell types including cardiomyocytes, endothelial cells, vascular smooth muscle cells, and inflammatory cells. While initial studies addressed transcriptional control of gene expression, epigenetics has been increasingly appreciated to also play an important role in this process through alterations in chromatin structure and gene accessibility. Chromatin-modifying proteins including enzymes that modulate DNA methylation, histone methylation, and histone acetylation can influence gene expression in numerous ways. These chromatin modifiers and their marks can promote or prevent transcription factor recruitment to regulatory regions of genes through modifications to DNA, histones, or the transcription factors themselves. This review will focus on the emerging question of how epigenetic modifiers and transcription factors interact to coordinately regulate gene expression in cardiovascular disease. While most studies have addressed the roles of either epigenetic or transcriptional control, our understanding of the integration of these processes is only just beginning. Interrogating these interactions is challenging, and improved technical approaches will be needed to fully dissect the temporal and spatial relationships between transcription factors, chromatin modifiers, and gene expression in cardiovascular disease. We summarize the current state of the field and provide perspectives on limitations and future directions. Through studies of epigenetic and transcriptional interactions, we can advance our understanding of the basic mechanisms of cardiovascular disease pathogenesis to develop novel therapeutics. PMID:28428957

Allergic rhinitis and inflammatory airway disease: interactions within the unified airspace.

PubMed

Marple, Bradley F

2010-01-01

Allergic rhinitis (AR), the most common chronic allergic condition in outpatient medicine, is associated with immense health care costs and socioeconomic consequences. AR's impact may be partly from interacting of respiratory conditions via allergic inflammation. This study was designed to review potential interactive mechanisms of AR and associated conditions and consider the relevance of a bidirectional "unified airway" respiratory inflammation model on diagnosis and treatment of inflammatory airway disease. MEDLINE was searched for pathophysiology and pathophysiological and epidemiologic links between AR and diseases of the sinuses, lungs, middle ear, and nasopharynx. Allergic-related inflammatory responses or neural and systemic processes fostering inflammatory changes distant from initial allergen provocation may link AR and comorbidities. Treating AR may benefit associated respiratory tract comorbidities. Besides improving AR outcomes, treatment inhibiting eosinophil recruitment and migration, normalizing cytokine profiles, and reducing asthma-associated health care use in atopic subjects would likely ameliorate other upper airway diseases such as acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyposis (NP), adenoidal hypertrophy, and otitis media with effusion. Epidemiological concordance of AR with several airway diseases conforms to a bidirectional "unified airway" respiratory inflammation model based on anatomic and histological upper and lower airway connections. Epidemiology and current understanding of inflammatory, humoral, and neural processes make links between AR and disorders including asthma, otitis media, NP, and CRS plausible. Combining AR with associated conditions increases disease burden; worsened associated illness may accompany worsened AR. AR pharmacotherapies include antihistamines, leukotriene antagonists, intranasal corticosteroids, and immunotherapy; treatments attenuating proinflammatory responses may also benefit associated conditions.

The impact of mobile health interventions on chronic disease outcomes in developing countries: a systematic review.

PubMed

Beratarrechea, Andrea; Lee, Allison G; Willner, Jonathan M; Jahangir, Eiman; Ciapponi, Agustín; Rubinstein, Adolfo

2014-01-01

Rates of chronic diseases will continue to rise in developing countries unless effective and cost-effective interventions are implemented. This review aims to discuss the impact of mobile health (m-health) on chronic disease outcomes in low- and middle-income countries (LMIC). Systematic literature searches were performed using CENTRAL, MEDLINE, EMBASE, and LILACS databases and gray literature. Scientific literature was searched to identify controlled studies evaluating cell phone voice and text message interventions to address chronic diseases in adults in low- or middle-income countries. Outcomes measured included morbidity, mortality, hospitalization rates, behavioral or lifestyle changes, process of care improvements, clinical outcomes, costs, patient-provider satisfaction, compliance, and health-related quality of life (HRQoL). From the 1,709 abstracts retrieved, 163 articles were selected for full text review, including 9 randomized controlled trials with 4,604 participants. Most of the studies addressed more than one outcome. Of the articles selected, six studied clinical outcomes, six studied processes of care, three examined healthcare costs, and two examined HRQoL. M-health positively impacted on chronic disease outcomes, improving attendance rates, clinical outcomes, and HRQoL, and was cost-effective. M-health is emerging as a promising tool to address access, coverage, and equity gaps in developing countries and low-resource settings. The results for m-health interventions showed a positive impact on chronic diseases in LMIC. However, a limiting factor of this review was the relatively small number of studies and patients enrolled, highlighting the need for more rigorous research in this area in developing countries.

The Protective Effect of Lipoic Acid on Selected Cardiovascular Diseases Caused by Age-Related Oxidative Stress

PubMed Central

Goraca, Anna

2015-01-01

Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system. PMID:25949771

Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction

PubMed Central

Wray, D. Walter; Amann, Markus

2016-01-01

The aging process appears to be a precursor to many age-related diseases, perhaps the most impactful of which is cardiovascular disease (CVD). Heart disease, a manifestation of CVD, is the leading cause of death in the USA, and heart failure (HF), a syndrome that develops as a consequence of heart disease, now affects almost six million American. Importantly, as this is an age-related disease, this number is likely to grow along with the ever-increasing elderly population. Hallmarks of the aging process and HF patients with a reduced ejection fraction (HFrEF) include exercise intolerance, premature fatigue, and limited oxygen delivery and utilization, perhaps as a consequence of diminished peripheral vascular function. Free radicals and oxidative stress have been implicated in this peripheral vascular dysfunction, as a redox imbalance may directly impact the function of the vascular endothelium. This review aims to bring together studies that have examined the impact of oxidative stress on peripheral vascular function and oxygen delivery and utilization with both healthy aging and HFrEF. PMID:27392715

Immunomodulatory Effects of Soybeans and Processed Soy Food Compounds.

PubMed

Tezuka, Hiroyuki; Imai, Shinjiro

2015-01-01

Inflammation is an immune response against both internal and external antigens in organisms, particularly in mammals, and includes both uncontrolled chronic and low-grade inflammations. Uncontrolled chronic inflammation often leads to severe diseases such as vascular disease, arthritis, cancer, diabete, allergy, and autoimmunity. On the other hand, low-grade inflammation is recognized as a relationship between obesity and risk of metabolic syndrome. Elevated production of pro-inflammatory cytokines and mediators is commonly observed in patients with uncontrolled or low-grade inflammation-associated diseases. Plants have been generated phytochemicals to overcome inflammations and infections through evolution. Phytochemicals belong to alkaloids, polyphenols, flavonoids, coumarins, and terpenoids. The consumption of soybeans plays a role in immune modulation through their components such as isoflavones, saponins, and anthocyanins. Recently, it was reported that the application of phytochemicals into patients with inflammatory diseases improves their symptoms. Therefore, it is important to identify novel phytochemicals with immunomodulatory activities. This review introduces and discusses recent advances and patents regarding soybean or processed soy food compounds which exhibit immunomodulatory activity in immune diseases, particularly allergy, by mediating the suppression of inflammatory pathways.

Does impaired socioemotional functioning account for behavioral dysexecutive disorders? Evidence from a transnosological study.

PubMed

Narme, Pauline; Roussel, Martine; Mouras, Harold; Krystkowiak, Pierre; Godefroy, Olivier

2017-01-01

Behavioral dysexecutive disorders are highly prevalent in patients with neurological diseases but cannot be explained by cognitive dysexecutive impairments. In fact, the underlying mechanisms are poorly understood. Given that socioemotional functioning underlies appropriate behavior, socioemotional impairments may contribute to the appearance of behavioral disorders. To investigate this issue, we performed a transnosological study. Seventy-five patients suffering from various neurological diseases (Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal lobar degeneration, and stroke) were included in the study. The patients were comprehensively assessed in terms of cognitive and behavioral dysexecutive disorders and socioemotional processes (facial emotion recognition and theory of mind). As was seen for cognitive and behavioral dysexecutive impairments, the prevalence of socioemotional impairments varied according to the diagnosis. Stepwise logistic regressions showed that (i) only cognitive executive indices predicted hypoactivity with apathy/abulia, (ii) theory of mind impairments predicted hyperactivity-distractibility-impulsivity and stereotyped/perseverative behaviors, and (iii) impaired facial emotion recognition predicted social behavior disorders. Several dysexecutive behavioral disorders are associated with an underlying impairment in socioemotional processes but not with cognitive indices of executive functioning (except for apathy). These results strongly suggest that some dysexecutive behavioral disorders are the outward signs of an underlying impairment in socioemotional processes.

Modeling Molecular and Cellular Aspects of Human Disease using the Nematode Caenorhabditis elegans

PubMed Central

Silverman, Gary A.; Luke, Cliff J.; Bhatia, Sangeeta R.; Long, Olivia S.; Vetica, Anne C.; Perlmutter, David H.; Pak, Stephen C.

2009-01-01

As an experimental system, Caenorhabditis elegans, offers a unique opportunity to interrogate in vivo the genetic and molecular functions of human disease-related genes. For example, C. elegans has provided crucial insights into fundamental biological processes such as cell death and cell fate determinations, as well as pathological processes such as neurodegeneration and microbial susceptibility. The C. elegans model has several distinct advantages including a completely sequenced genome that shares extensive homology with that of mammals, ease of cultivation and storage, a relatively short lifespan and techniques for generating null and transgenic animals. However, the ability to conduct unbiased forward and reverse genetic screens in C. elegans remains one of the most powerful experimental paradigms for discovering the biochemical pathways underlying human disease phenotypes. The identification of these pathways leads to a better understanding of the molecular interactions that perturb cellular physiology, and forms the foundation for designing mechanism-based therapies. To this end, the ability to process large numbers of isogenic animals through automated work stations suggests that C. elegans, manifesting different aspects of human disease phenotypes, will become the platform of choice for in vivo drug discovery and target validation using high-throughput/content screening technologies. PMID:18852689

The effect of a prudent adaptive behaviour on disease transmission

NASA Astrophysics Data System (ADS)

Scarpino, Samuel V.; Allard, Antoine; Hébert-Dufresne, Laurent

2016-11-01

The spread of disease can be slowed by certain aspects of real-world social networks, such as clustering and community structure, and of human behaviour, including social distancing and increased hygiene, many of which have already been studied. Here, we consider a model in which individuals with essential societal roles--be they teachers, first responders or health-care workers--fall ill, and are replaced with healthy individuals. We refer to this process as relational exchange, and incorporate it into a dynamic network model to demonstrate that replacing individuals can accelerate disease transmission. We find that the effects of this process are trivial in the context of a standard mass-action model, but dramatic when considering network structure, featuring accelerating spread, discontinuous transitions and hysteresis loops. This result highlights the inability of mass-action models to account for many behavioural processes. Using empirical data, we find that this mechanism parsimoniously explains observed patterns across 17 influenza outbreaks in the USA at a national level, 25 years of influenza data at the state level, and 19 years of dengue virus data from Puerto Rico. We anticipate that our findings will advance the emerging field of disease forecasting and better inform public health decision making during outbreaks.

Comparing different policy scenarios to reduce the consumption of ultra-processed foods in UK: impact on cardiovascular disease mortality using a modelling approach.

PubMed

Moreira, Patricia V L; Baraldi, Larissa Galastri; Moubarac, Jean-Claude; Monteiro, Carlos Augusto; Newton, Alex; Capewell, Simon; O'Flaherty, Martin

2015-01-01

The global burden of non-communicable diseases partly reflects growing exposure to ultra-processed food products (UPPs). These heavily marketed UPPs are cheap and convenient for consumers and profitable for manufacturers, but contain high levels of salt, fat and sugars. This study aimed to explore the potential mortality reduction associated with future policies for substantially reducing ultra-processed food intake in the UK. We obtained data from the UK Living Cost and Food Survey and from the National Diet and Nutrition Survey. By the NOVA food typology, all food items were categorized into three groups according to the extent of food processing: Group 1 describes unprocessed/minimally processed foods. Group 2 comprises processed culinary ingredients. Group 3 includes all processed or ultra-processed products. Using UK nutrient conversion tables, we estimated the energy and nutrient profile of each food group. We then used the IMPACT Food Policy model to estimate reductions in cardiovascular mortality from improved nutrient intakes reflecting shifts from processed or ultra-processed to unprocessed/minimally processed foods. We then conducted probabilistic sensitivity analyses using Monte Carlo simulation. Approximately 175,000 cardiovascular disease (CVD) deaths might be expected in 2030 if current mortality patterns persist. However, halving the intake of Group 3 (processed) foods could result in approximately 22,055 fewer CVD related deaths in 2030 (minimum estimate 10,705, maximum estimate 34,625). An ideal scenario in which salt and fat intakes are reduced to the low levels observed in Group 1 and 2 could lead to approximately 14,235 (minimum estimate 6,680, maximum estimate 22,525) fewer coronary deaths and approximately 7,820 (minimum estimate 4,025, maximum estimate 12,100) fewer stroke deaths, comprising almost 13% mortality reduction. This study shows a substantial potential for reducing the cardiovascular disease burden through a healthier food system. It highlights the crucial importance of implementing healthier UK food policies.

Transfer RNA and human disease.

PubMed

Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M

2014-01-01

Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

Participation of group I p21-activated kinases in neuroplasticity.

PubMed

Koth, André P; Oliveira, Bruno R; Parfitt, Gustavo M; Buonocore, Juliana de Quadros; Barros, Daniela M

2014-01-01

PAKs are a family of serine/threonine protein kinases activated by small GTPases of the Rho family, including Rac and Cdc42, and are categorized into group I (isoforms 1, 2 and 3) and group II (isoforms 4, 5 and 6). PAK1 and PAK3 are critically involved in biological mechanisms associated with neurodevelopment, neuroplasticity and maturation of the nervous system, and changes in their activity have been detected in pathological disorders, such as Alzheimer's disease, Huntington's disease and mental retardation. The group I PAKs have been associated with neurological processes due to their involvement in intracellular mechanisms that result in molecular and cellular morphological alterations that promote cytoskeletal outgrowth, increasing the efficiency of synaptic transmission. Their substrates in these processes include other intracellular signaling molecules, such as Raf, Mek and LIMK, as well as other components of the cytoskeleton, such as MLC and FLNa. In this review, we describe the characteristics of group I PAKs, such as their molecular structure, mechanisms of activation and importance in the neurobiological processes involved in synaptic plasticity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Employing image processing techniques for cancer detection using microarray images.

PubMed

Dehghan Khalilabad, Nastaran; Hassanpour, Hamid

2017-02-01

Microarray technology is a powerful genomic tool for simultaneously studying and analyzing the behavior of thousands of genes. The analysis of images obtained from this technology plays a critical role in the detection and treatment of diseases. The aim of the current study is to develop an automated system for analyzing data from microarray images in order to detect cancerous cases. The proposed system consists of three main phases, namely image processing, data mining, and the detection of the disease. The image processing phase performs operations such as refining image rotation, gridding (locating genes) and extracting raw data from images the data mining includes normalizing the extracted data and selecting the more effective genes. Finally, via the extracted data, cancerous cell is recognized. To evaluate the performance of the proposed system, microarray database is employed which includes Breast cancer, Myeloid Leukemia and Lymphomas from the Stanford Microarray Database. The results indicate that the proposed system is able to identify the type of cancer from the data set with an accuracy of 95.45%, 94.11%, and 100%, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Regulation of MicroRNAs-Mediated Autophagic Flux: A New Regulatory Avenue for Neurodegenerative Diseases With Focus on Prion Diseases

PubMed Central

Shah, Syed Zahid Ali; Zhao, Deming; Hussain, Tariq; Sabir, Naveed; Yang, Lifeng

2018-01-01

Prion diseases are fatal neurological disorders affecting various mammalian species including humans. Lack of proper diagnostic tools and non-availability of therapeutic remedies are hindering the control strategies for prion diseases. MicroRNAs (miRNAs) are abundant endogenous short non-coding essential RNA molecules that negatively regulate the target genes after transcription. Several biological processes depend on miRNAs, and altered profiles of these miRNAs are potential biomarkers for various neurodegenerative diseases, including prion diseases. Autophagic flux degrades the misfolded prion proteins to reduce chronic endoplasmic reticulum stress and enhance cell survival. Recent evidence suggests that specific miRNAs target and regulate the autophagic mechanism, which is critical for alleviating cellular stress. miRNAs-mediated regulation of these specific proteins involved in the autophagy represents a new target with highly significant therapeutic prospects. Here, we will briefly describe the biology of miRNAs, the use of miRNAs as potential biomarkers with their credibility, the regulatory mechanism of miRNAs in major neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and prion diseases, degradation pathways for aggregated prion proteins, the role of autophagy in prion diseases. Finally, we will discuss the miRNAs-modulated autophagic flux in neurodegenerative diseases and employ them as potential therapeutic intervention strategy in prion diseases. PMID:29867448

Lung disease and coal mining: what pulmonologists need to know.

PubMed

Go, Leonard H T; Krefft, Silpa D; Cohen, Robert A; Rose, Cecile S

2016-03-01

Coal mine workers are at risk for a range of chronic respiratory diseases including coal workers' pneumoconiosis, diffuse dust-related fibrosis, and chronic obstructive pulmonary disease. The purpose of this review is to describe coal mining processes and associated exposures to inform the diagnostic evaluation of miners with respiratory symptoms. Although rates of coal workers' pneumoconiosis declined after regulations were enacted in the 1970s, more recent data shows a reversal in this downward trend. Rapidly progressive pneumoconiosis with progressive massive fibrosis (complicated coal workers' pneumoconiosis) is being observed with increased frequency in United States coal miners, with histologic findings of silicosis and mixed-dust pneumoconiosis. There is increasing evidence of decline in lung function in individuals with pneumoconiosis. Multiple recent cohort studies suggest increased risk of lung cancer in coal miners. A detailed understanding of coal mining methods and processes allows clinicians to better evaluate and confirm chronic lung diseases caused by inhalational hazards in the mine atmosphere.

Splicing regulatory factors, ageing and age-related disease.

PubMed

Latorre, Eva; Harries, Lorna W

2017-07-01

Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease. Copyright © 2017 Elsevier B.V. All rights reserved.

A fast-response two-photon fluorescent probe for imaging endogenous H2O2 in living cells and tissues

NASA Astrophysics Data System (ADS)

Lu, Yanan; Shi, Xiaomin; Fan, Wenlong; Black, Cory A.; Lu, Zhengliang; Fan, Chunhua

2018-02-01

As a second messenger, hydrogen peroxide plays significant roles in numerous physiological and pathological processes and is related to various diseases including inflammatory disease, diabetes, neurodegenerative disorders, cardiovascular disease and Alzheimer's disease. Two-photon (TP) fluorescent probes reported for the detection of endogenous H2O2 are rare and most have drawbacks such as slow response and low sensitivity. In this report, we demonstrate a simple H2O2-specific TP fluorescent probe (TX-HP) containing a two-photon dye 6-hydroxy-2,3,4,4a-tetrahydro-1H-xanthen-1-one (TX) on the modulation of the ICT process. The probe exhibits a rapid fluorescent response to H2O2 in 9 min with both high sensitivity and selectivity. The probe can detect exogenous H2O2 in living cells. Furthermore, the probe is successfully utilized for imaging H2O2 in liver tissues.

Potential of PET-MRI for imaging of non-oncologic musculoskeletal disease.

PubMed

Kogan, Feliks; Fan, Audrey P; Gold, Garry E

2016-12-01

Early detection of musculoskeletal disease leads to improved therapies and patient outcomes, and would benefit greatly from imaging at the cellular and molecular level. As it becomes clear that assessment of multiple tissues and functional processes are often necessary to study the complex pathogenesis of musculoskeletal disorders, the role of multi-modality molecular imaging becomes increasingly important. New positron emission tomography-magnetic resonance imaging (PET-MRI) systems offer to combine high-resolution MRI with simultaneous molecular information from PET to study the multifaceted processes involved in numerous musculoskeletal disorders. In this article, we aim to outline the potential clinical utility of hybrid PET-MRI to these non-oncologic musculoskeletal diseases. We summarize current applications of PET molecular imaging in osteoarthritis (OA), rheumatoid arthritis (RA), metabolic bone diseases and neuropathic peripheral pain. Advanced MRI approaches that reveal biochemical and functional information offer complementary assessment in soft tissues. Additionally, we discuss technical considerations for hybrid PET-MR imaging including MR attenuation correction, workflow, radiation dose, and quantification.

Role of macrophage migration inhibitory factor in age-related lung disease

PubMed Central

Sauler, Maor; Bucala, Richard

2015-01-01

The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease. PMID:25957294

A common presentation to an uncommon disease. Penile Mondor's disease: a case report and literature review.

PubMed

Walsh, John C; Poimboeuf, Sabré; Garvin, Daniel S

2014-01-01

Penile Mondor's disease, or superficial thrombophlebitis of the dorsal vein of the penis, is a relatively uncommon but potentially anxiety-inducing self-limiting condition that should be easily recognizable by any primary care practitioner. It typically presents with a cord-like mass and pain to the dorsal penis and has a myriad of causes, including trauma, excessive sexual activity, excessive exercise, or malignancy. Although Penile Mondor's disease is typically a clinical diagnosis, Doppler ultrasound is the initial imaging modality of choice if there is question or doubt about the diagnosis. Accurate diagnosis and reassurance about the condition's benign and self-limiting nature assuages most patients' fears. Treatment is primarily symptomatic but may vary depending on possible underlying disease processes.

Multicenter evaluation of signalment and comorbid conditions associated with aortic thrombotic disease in dogs.

PubMed

Winter, Randolph L; Budke, Christine M

2017-08-15

OBJECTIVE To assess signalment and concurrent disease processes in dogs with aortic thrombotic disease (ATD). DESIGN Retrospective case-control study. ANIMALS Dogs examined at North American veterinary teaching hospitals from 1985 through 2011 with medical records submitted to the Veterinary Medical Database. PROCEDURES Medical records were reviewed to identify dogs with a diagnosis of ATD (case dogs). Five control dogs without a diagnosis of ATD were then identified for every case dog. Data were collected regarding dog age, sex, breed, body weight, and concurrent disease processes. RESULTS ATD was diagnosed in 291 of the 984,973 (0.03%) dogs included in the database. The odds of a dog having ATD did not differ significantly by sex, age, or body weight. Compared with mixed-breed dogs, Shetland Sheepdogs had a significantly higher odds of ATD (OR, 2.59). Protein-losing nephropathy (64/291 [22%]) was the most commonly recorded concurrent disease in dogs with ATD. CONCLUSIONS AND CLINICAL RELEVANCE Dogs with ATD did not differ significantly from dogs without ATD in most signalment variables. Contrary to previous reports, cardiac disease was not a common concurrent diagnosis in dogs with ATD.

Integrated sequence analysis pipeline provides one-stop solution for identifying disease-causing mutations.

PubMed

Hu, Hao; Wienker, Thomas F; Musante, Luciana; Kalscheuer, Vera M; Kahrizi, Kimia; Najmabadi, Hossein; Ropers, H Hilger

2014-12-01

Next-generation sequencing has greatly accelerated the search for disease-causing defects, but even for experts the data analysis can be a major challenge. To facilitate the data processing in a clinical setting, we have developed a novel medical resequencing analysis pipeline (MERAP). MERAP assesses the quality of sequencing, and has optimized capacity for calling variants, including single-nucleotide variants, insertions and deletions, copy-number variation, and other structural variants. MERAP identifies polymorphic and known causal variants by filtering against public domain databases, and flags nonsynonymous and splice-site changes. MERAP uses a logistic model to estimate the causal likelihood of a given missense variant. MERAP considers the relevant information such as phenotype and interaction with known disease-causing genes. MERAP compares favorably with GATK, one of the widely used tools, because of its higher sensitivity for detecting indels, its easy installation, and its economical use of computational resources. Upon testing more than 1,200 individuals with mutations in known and novel disease genes, MERAP proved highly reliable, as illustrated here for five families with disease-causing variants. We believe that the clinical implementation of MERAP will expedite the diagnostic process of many disease-causing defects. © 2014 WILEY PERIODICALS, INC.

Oxidative stress as a mechanism of added sugar-induced cardiovascular disease.

PubMed

Prasad, Kailash; Dhar, Indu

2014-12-01

Added sugars comprising of table sugar, brown sugar, corn syrup, maple syrup, honey, molasses, and other sweeteners in the prepared processed foods and beverages have been implicated in the pathophysiology of cardiovascular diseases. This article deals with the reactive oxygen species (ROS) as a mechanism of sugar-induced cardiovascular diseases. There is an association between the consumption of high levels of serum glucose with cardiovascular diseases. Various sources of sugar-induced generation of ROS, including mitochondria, nicotinamide adenine dinucleotide phosphate-oxidase, advanced glycation end products, insulin, and uric acid have been discussed. The mechanism by which ROS induce the development of atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias have been discussed in detail. In conclusion, the data suggest that added sugars induce atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias and that these effects of added sugars are mediated through ROS.

The potential of epigenetic therapies in neurodegenerative diseases

PubMed Central

Coppedè, Fabio

2014-01-01

Available treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease, do not arrest disease progression but mainly help keeping patients from getting worse for a limited period of time. Increasing evidence suggests that epigenetic mechanisms such as DNA methylation and histone tail modifications are dynamically regulated in neurons and play a fundamental role in learning and memory processes. In addition, both global and gene-specific epigenetic changes and deregulated expression of the writer and eraser proteins of epigenetic marks are believed to contribute to the onset and progression of neurodegeneration. Studies in animal models of neurodegenerative diseases have highlighted the potential role of epigenetic drugs, including inhibitors of histone deacetylases and methyl donor compounds, in ameliorating the cognitive symptoms and preventing or delaying the motor symptoms of the disease, thereby opening the way for a potential application in human pathology. PMID:25071843

The German government's global health strategy--a strategy also to support research and development for neglected diseases?

PubMed

Fehr, Angela; Razum, Oliver

2014-01-01

Neglected tropical infectious diseases as well as rare diseases are characterized by structural research and development (R&D) deficits. The market fails for these disease groups. Consequently, to meet public health and individual patient needs, political decision makers have to develop strategies at national and international levels to make up for this R&D deficit. The German government recently published its first global health strategy. The strategy underlines the German government's commitment to strengthening global health governance. We find, however, that the strategy lacks behind the international public health endeavors for neglected diseases. It fails to make reference to the ongoing debate on a global health agreement. Neither does it outline a comprehensive national strategy to promote R&D into neglected diseases, which would integrate existing R&D activities in Germany and link up to the international debate on sustainable, needs-based R&D and affordable access. This despite the fact that only recently, in a consensus-building process, a National Plan of Action for rare diseases was successfully developed in Germany which could serve as a blueprint for a similar course of action for neglected diseases. We recommend that, without delay, a structured process be initiated in Germany to explore all options to promote R&D for neglected diseases, including a global health agreement.

Implementation of a drug-use and disease-state management program.

PubMed

Skledar, S J; Hess, M M

2000-12-15

A drug-use and disease-state management (DUDSM) program was instituted in 1996 at a teaching hospital associated with a large nonprofit health care system. The program's goals are to optimize pharmacotherapeutic regimens, evaluate health outcomes of identified disease states, and evaluate the economic impact of pharmacotherapeutic options for given disease states by developing practice guidelines. Through a re-engineering process, resources within the pharmacy department were identified that could be devoted to the DUDSM program, including the use of clinical pharmacy specialists, promotion of staff pharmacists into the DUDSM program, a pharmacy technician, and information systems support. A strength of the program is its systematic approach for developing and implementing new initiatives, as well as monitoring compliance with all initiatives on an ongoing basis. The initiative-design process incorporates continuous quality improvement principles, outcome design and evaluation, competency assessment for all pharmacists, multidisciplinary collaboration, and sophisticated information systems. Seventy-five initiatives have been implemented, ranging from simple dose-optimization strategies for specific drugs to complicated practice guidelines for managing specific disease states. Improved patient outcomes have been documented, including reduced length of stay, postsurgical wound infection, adverse drug reactions, and medication errors. Documented cost savings exceeded $4 million annually for fiscal years 1996-97 through 1999-2000. Overall compliance with DUDSM initiatives exceeds 80%, and physician service profiling has been initiated to monitor variant prescribing. The DUDSM program has successfully integrated practice guidelines into therapeutic decision-making, resulting in improved patient-care outcomes and cost savings.

Does disease management improve clinical and economic outcomes in patients with chronic diseases? A systematic review.

PubMed

Ofman, Joshua J; Badamgarav, Enkhe; Henning, James M; Knight, Kevin; Gano, Anacleto D; Levan, Rebecka K; Gur-Arie, Shoval; Richards, Margaret S; Hasselblad, Vic; Weingarten, Scott R

2004-08-01

To assess the clinical and economic effects of disease management in patients with chronic diseases. Electronic databases were searched for English-language articles from 1987 to 2001. Articles were included if they used a systematic approach to care and evaluated patients with chronic disease, reported objective measurements of the processes or outcomes of care, and employed acceptable experimental or quasi-experimental study designs as defined by the Cochrane Effective Practice and Organization of Care Group. Two reviewers evaluated 16,917 titles and identified 102 studies that met the inclusion criteria. Identified studies represented 11 chronic conditions: depression, diabetes, rheumatoid arthritis, chronic pain, coronary artery disease, asthma, heart failure, back pain, chronic obstructive pulmonary disease, hypertension, and hyperlipidemia. Disease management programs for patients with depression had the highest percentage of comparisons (48% [41/86]) showing substantial improvements in patient care, whereas programs for patients with chronic obstructive pulmonary disease (9% [2/22]) or chronic pain (8% [1/12]) appeared to be the least effective. Of the outcomes more frequently studied, disease management appeared to improve patient satisfaction (71% [12/17]), patient adherence (47% [17/36]), and disease control (45% [33/74]) most commonly and cost-related outcomes least frequently (11% to 16%). Disease management programs were associated with marked improvements in many different processes and outcomes of care. Few studies demonstrated a notable reduction in costs. Further research is needed to understand how disease management can most effectively improve the quality and cost of care for patients with chronic diseases.

Ebola Virus Disease: essential public health principles for clinicians.

PubMed

Koenig, Kristi L; Majestic, Cassondra; Burns, Michael J

2014-11-01

Ebola Virus Disease (EVD) has become a public health emergency of international concern. The World Health Organization and Centers for Disease Control and Prevention have developed guidance to educate and inform healthcare workers and travelers worldwide. Symptoms of EVD include abrupt onset of fever, myalgias, and headache in the early phase, followed by vomiting, diarrhea and possible progression to hemorrhagic rash, life-threatening bleeding, and multi-organ failure in the later phase. The disease is not transmitted via airborne spread like influenza, but rather from person-to-person, or animal to person, via direct contact with bodily fluids or blood. It is crucial that emergency physicians be educated on disease presentation and how to generate a timely and accurate differential diagnosis that includes exotic diseases in the appropriate patient population. A patient should be evaluated for EVD when both suggestive symptoms, including unexplained hemorrhage, AND risk factors within 3 weeks prior, such as travel to an endemic area, direct handling of animals from outbreak areas, or ingestion of fruit or other uncooked foods contaminated with bat feces containing the virus are present. There are experimental therapies for treatment of EVD virus; however the mainstay of therapy is supportive care. Emergency department personnel on the frontlines must be prepared to rapidly identify and isolate febrile travelers if indicated. All healthcare workers involved in care of EVD patients should wear personal protective equipment. Despite the intense media focus on EVD rather than other threats, emergency physicians must master and follow essential public health principles for management of all infectious diseases. This includes not only identification and treatment of individuals, but also protection of healthcare workers and prevention of spread, keeping in mind the possibility of other more common disease processes.

Survey of Communicable Diseases Surveillance System in Hospitals of Iran: A Qualitative Approach

PubMed Central

Dehcheshmeh, Nayeb Fadaei; Arab, Mohammad; Foroushani, Abbas Rahimi; Farzianpour, Fereshteh

2016-01-01

Background: Communicable Disease Surveillance and reporting is one of the key elements to combat against diseases and their control. Fast and timely recognition of communicable diseases can be helpful in controlling of epidemics. One of the main sources of management of communicable diseases reporting is hospitals that collect communicable diseases’ reports and send them to health authorities. One of the focal problems and challenges in this regard is incomplete and imprecise reports from hospitals. In this study, while examining the implementation processes of the communicable diseases surveillance in hospitals, non-medical people who were related to the program have been studied by a qualitative approach. Methods: This study was conducted using qualitative content analysis method. Participants in the study included 36 informants, managers, experts associated with health and surveillance of communicable diseases that were selected using targeted sampling and with diverse backgrounds and work experience (different experiences in primary health surveillance and treatment, Ministry levels, university staff and operations (hospitals and health centers) and sampling was continued until arrive to data saturation. Results: Interviews were analyzed after the elimination of duplicate codes and integration of them. Finally, 73 codes were acquired and categorized in 6 major themes and 21 levels. The main themes included: policy making and planning, development of resources, organizing, collaboration and participation, surveillance process, and monitoring and evaluation of the surveillance system. In point of interviewees, attention to these themes is necessary to develop effective and efficient surveillance system for communicable diseases. Conclusion: Surveillance system in hospitals is important in developing proper macro - policies in health sector, adoption of health related decisions and preventive plans appropriate to the existing situation. Compilation, changing, improving, monitoring and continuous updating of surveillance systems can play a significant role in its efficiency and effectiveness. In the meantime, policy makers’ and senior managers’ support in development and implementation of communicable disease surveillance’ plans and their reporting plays a key and core role. PMID:27157154

A Review of Podocyte Biology.

PubMed

Garg, Puneet

2018-05-31

Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement. Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting. © 2018 S. Karger AG, Basel.

Resilience to health challenges is related to different ways of thinking: mediators of physical and emotional quality of life in a heterogeneous rare-disease cohort.

PubMed

Schwartz, Carolyn E; Michael, Wesley; Rapkin, Bruce D

2017-11-01

We sought to understand what distinguishes people who confront health challenges but still manage to thrive. This study investigated whether resilience helps to explain the impact of health challenges on quality of life (QOL) outcomes, and how resilience relates to appraisal. A web-based survey of rare-disease panel participants included the Centers for Disease Control Healthy Days Core Module, the PROMIS-10, and comorbidities. The QOL Appraisal Profile-v2 assessed cognitive processes underlying QOL. Resilience was operationalized statistically using residual modeling, and hierarchical regressions tested the mediation hypothesis that resilience accounts for a significant amount of the relationship of appraisal to QOL. The study sample (n = 3,324; mean age 50; 86% female; 90% White) represented a range of diagnostic codes, with cancer and diseases of the nervous system being the most prevalent health conditions. After adjusting for comorbidities (catalysts), resilience was associated with better physical and emotional functioning, and different appraisal processes were associated with better or worse physical or emotional functioning. After controlling for catalysts, 62% of the association of Physical Functioning and 23% of the association between Emotional Functioning and appraisal were mediated by resilience. Physical and emotional resilience comprised some of the same appraisal processes, but physically resilient people were characterized by more appraisal processes than their emotionally resilient counterparts. Resilient people employ different appraisal processes than non-resilient people, and these processes differ for physical and emotional outcomes. Resilience was a stronger mediator of the relationship between physical rather than emotional functioning and appraisal.

Changes in connectivity of the posterior default network node during visual processing in mild cognitive impairment: staged decline between normal aging and Alzheimer's disease.

PubMed

Krajcovicova, Lenka; Barton, Marek; Elfmarkova-Nemcova, Nela; Mikl, Michal; Marecek, Radek; Rektorova, Irena

2017-12-01

Visual processing difficulties are often present in Alzheimer's disease (AD), even in its pre-dementia phase (i.e. in mild cognitive impairment, MCI). The default mode network (DMN) modulates the brain connectivity depending on the specific cognitive demand, including visual processes. The aim of the present study was to analyze specific changes in connectivity of the posterior DMN node (i.e. the posterior cingulate cortex and precuneus, PCC/P) associated with visual processing in 17 MCI patients and 15 AD patients as compared to 18 healthy controls (HC) using functional magnetic resonance imaging. We used psychophysiological interaction (PPI) analysis to detect specific alterations in PCC connectivity associated with visual processing while controlling for brain atrophy. In the HC group, we observed physiological changes in PCC connectivity in ventral visual stream areas and with PCC/P during the visual task, reflecting the successful involvement of these regions in visual processing. In the MCI group, the PCC connectivity changes were disturbed and remained significant only with the anterior precuneus. In between-group comparison, we observed significant PPI effects in the right superior temporal gyrus in both MCI and AD as compared to HC. This change in connectivity may reflect ineffective "compensatory" mechanism present in the early pre-dementia stages of AD or abnormal modulation of brain connectivity due to the disease pathology. With the disease progression, these changes become more evident but less efficient in terms of compensation. This approach can separate the MCI from HC with 77% sensitivity and 89% specificity.

A review of blepharochalasis and other causes of the lax, wrinkled eyelid.

PubMed

Held, J L; Schneiderman, P

1990-02-01

Cosmetically unappealing lax, wrinkled eyelid skin may result from various processes including connective tissue diseases, natural aging, and blepharochalasis. Since the end-stage eyelid changes due to several different processes are similar, the presence or absence of prior chronic or recurrent eyelid edema is an important differentiating point. We review blepharochalasis and provide a logical approach to its differential diagnosis.

Modeling the inactivatin of Escherichia coli 0157:H7 and uropathogenic E. coli in ground beef by high pressure processing and citral

USDA-ARS?s Scientific Manuscript database

Disease causing Escherichia coli commonly found in meat and poultry include intestinal pathogenic E. coli (iPEC) as well as extraintestinal types such as the Uropathogenic E. coli (UPEC). In this study we compared the resistance of iPEC (O157:H7) to UPEC in ground beef using High Pressure Processing...

Modeling the inactivation of Escherichia coli 0157:H7 and uropathogenic E.coli in ground chicken by high pressure processing and thymol

USDA-ARS?s Scientific Manuscript database

Disease causing Escherichia coli commonly found in meat and poultry include intestinal pathogenic E. coli (iPEC) as well as extraintestinal types such as the Uropathogenic E. coli (UPEC). In this study we compare the resistance of iPEC (O157:H7) to UPEC in chicken meat using High Pressure Processing...

Enteric disease surveillance under the AFHSC-GEIS: Current efforts, landscape analysis and vision forward

PubMed Central

2011-01-01

The mission of the Armed Forces Health Surveillance Center, Division of Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) is to support global public health and to counter infectious disease threats to the United States Armed Forces, including newly identified agents or those increasing in incidence. Enteric diseases are a growing threat to U.S. forces, which must be ready to deploy to austere environments where the risk of exposure to enteropathogens may be significant and where routine prevention efforts may be impractical. In this report, the authors review the recent activities of AFHSC-GEIS partner laboratories in regards to enteric disease surveillance, prevention and response. Each partner identified recent accomplishments, including support for regional networks. AFHSC/GEIS partners also completed a Strengths, Weaknesses, Opportunities and Threats (SWOT) survey as part of a landscape analysis of global enteric surveillance efforts. The current strengths of this network include excellent laboratory infrastructure, equipment and personnel that provide the opportunity for high-quality epidemiological studies and test platforms for point-of-care diagnostics. Weaknesses include inconsistent guidance and a splintered reporting system that hampers the comparison of data across regions or longitudinally. The newly chartered Enterics Surveillance Steering Committee (ESSC) is intended to provide clear mission guidance, a structured project review process, and central data management and analysis in support of rationally directed enteric disease surveillance efforts. PMID:21388567

Apelin/APJ system: A novel potential therapy target for kidney disease.

PubMed

Huang, Zhen; Wu, Lele; Chen, Linxi

2018-05-01

Apelin is an endogenous ligand of seven-transmembrane G protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease. © 2017 Wiley Periodicals, Inc.

Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

PubMed Central

Talero, Elena; García-Mauriño, Sofía; Ávila-Román, Javier; Rodríguez-Luna, Azahara; Alcaide, Antonio; Motilva, Virginia

2015-01-01

The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress to squamous cell carcinoma. Chronic inflammatory states expose these patients to a number of signals with tumorigenic effects, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) activation, pro-inflammatory cytokines and prostaglandins release and ROS production. In addition, the participation of inflammasomes, autophagy and sirtuins has been demonstrated in pathological processes such as inflammation and cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon and skin cancer chemopreventive properties of substances from marine environment, including microalgae species and their products (carotenoids, fatty acids, glycolipids, polysaccharides and proteins). This review summarizes the main mechanisms of actions of these compounds in the chemoprevention of these cancers. These actions include suppression of cell proliferation, induction of apoptosis, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity. PMID:26437418

Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation.

PubMed

Kauwe, John S K; Bailey, Matthew H; Ridge, Perry G; Perry, Rachel; Wadsworth, Mark E; Hoyt, Kaitlyn L; Staley, Lyndsay A; Karch, Celeste M; Harari, Oscar; Cruchaga, Carlos; Ainscough, Benjamin J; Bales, Kelly; Pickering, Eve H; Bertelsen, Sarah; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M

2014-10-01

Cerebrospinal fluid (CSF) 42 amino acid species of amyloid beta (Aβ42) and tau levels are strongly correlated with the presence of Alzheimer's disease (AD) neuropathology including amyloid plaques and neurodegeneration and have been successfully used as endophenotypes for genetic studies of AD. Additional CSF analytes may also serve as useful endophenotypes that capture other aspects of AD pathophysiology. Here we have conducted a genome-wide association study of CSF levels of 59 AD-related analytes. All analytes were measured using the Rules Based Medicine Human DiscoveryMAP Panel, which includes analytes relevant to several disease-related processes. Data from two independently collected and measured datasets, the Knight Alzheimer's Disease Research Center (ADRC) and Alzheimer's Disease Neuroimaging Initiative (ADNI), were analyzed separately, and combined results were obtained using meta-analysis. We identified genetic associations with CSF levels of 5 proteins (Angiotensin-converting enzyme (ACE), Chemokine (C-C motif) ligand 2 (CCL2), Chemokine (C-C motif) ligand 4 (CCL4), Interleukin 6 receptor (IL6R) and Matrix metalloproteinase-3 (MMP3)) with study-wide significant p-values (p<1.46×10-10) and significant, consistent evidence for association in both the Knight ADRC and the ADNI samples. These proteins are involved in amyloid processing and pro-inflammatory signaling. SNPs associated with ACE, IL6R and MMP3 protein levels are located within the coding regions of the corresponding structural gene. The SNPs associated with CSF levels of CCL4 and CCL2 are located in known chemokine binding proteins. The genetic associations reported here are novel and suggest mechanisms for genetic control of CSF and plasma levels of these disease-related proteins. Significant SNPs in ACE and MMP3 also showed association with AD risk. Our findings suggest that these proteins/pathways may be valuable therapeutic targets for AD. Robust associations in cognitively normal individuals suggest that these SNPs also influence regulation of these proteins more generally and may therefore be relevant to other diseases.

Process evaluation of a regional public health model to reduce chronic disease through policy and systems changes, Washington State, 2010-2014.

PubMed

Walkinshaw, Lina P; Mason, Caitlin; Allen, Claire L; Vu, Thuy; Nandi, Paj; Santiago, Patti Migliore; Hannon, Peggy A

2015-03-19

Although the regionalization of public health systems has been well documented in the case of emergency preparedness, there is little literature on the application of regional approaches to other aspects of public health. From 2011 through 2014 the Washington State Department of Health implemented a Community Transformation Grant to support community-level policy and systems changes to decrease chronic disease risk factors and increase access to clinical preventive services. The Department of Health implemented the grant through a regional model, grouping 32 of the state's 35 local health jurisdictions into 5 regions. Our process evaluation identifies the challenges and facilitators to Community Transformation Grant planning and implementation. We conducted 34 key informant interviews with people directly involved in the implementation of the Community Transformation Grant. We interviewed state and local partners, including representatives from each region, the Department of Health, external consultants, and regional partners. We collected data from October 2013 through July 2014. Challenges for planning, building, and implementing a regional model for chronic disease prevention included stakeholder buy-in, regional geography, and communication; facilitators included shared regional history and infrastructure, strong leadership, collaborative relationships, shared vision and goals, sufficient funding, and direct technical assistance and training. Lessons learned in Washington State provide a foundation for other states interested in using a regional approach to reduce chronic disease risk. Policy and systems changes require adequate time, funding, and staffing. States and funders should work closely with local leaders to address these challenges and facilitators.

Animal health: foundation of a safe, secure, and abundant food supply.

PubMed

DeHaven, W Ron; Goldberg, Ruth

2006-01-01

During the past century, reductions in animal diseases have resulted in a safer, more uniform, and more economical food supply. In the United States, the passage of the 1906 Federal Meat Inspection Act mandated better sanitary conditions for slaughter and processing, as well as inspection of live animals and their processed products. Following World War II, Congress passed the Poultry Products Inspection Act. Both acts are regulated by the Food Safety and Inspection Service (FSIS) of the US Department of Agriculture (USDA). The USDA's Animal and Plant Health Inspection Service (APHIS) is responsible for regulations governing the health of live animals prior to slaughter. This article is a brief overview of the ways in which the current predominance of zoonotics among emerging diseases underscores the importance of veterinary health professionals and the need for continued coordination between animal-health and public-health officials. Examples of intersections between animal- and public-health concerns include bovine spongiform encephalopathy (BSE) and Johne's disease, as well as extending beyond food safety to diseases such as avian influenza (AI). In the United States, we have in place an extensive public and private infrastructure to address animal-health issues, including the necessary expertise and resources to address animal-health emergencies. However, many challenges remain, including a critical shortage of food-animal veterinarians. These challenges can be met by recruiting and training a cadre of additional food-supply veterinarians, pursuing new technologies, collaborating with public-health officials to create solutions, and sending a clear and consistent message to the public about important animal-health issues.

Recent developments in the surgical management of perianal fistula for Crohn’s disease

PubMed Central

Geltzeiler, Cristina B.; Wieghard, Nicole; Tsikitis, Vassiliki L.

2014-01-01

Perianal manifestations of Crohn’s disease (CD) are common and, of them, fistulas are the most common. Perianal fistulas can be extremely debilitating for patients and are often very challenging for clinicians to treat. CD perianal fistulas usually require multidisciplinary and multimodality treatment, including both medical and surgical approaches. The majority of patients require multiple surgical interventions. CD patients with perianal fistulas have a high rate of primary non-healing, surgical morbidity, and high recurrence rates. This has led to constant efforts to improve surgical management of this disease process. PMID:25331917

Magnesium: Nutrition and Homoeostasis.

PubMed

Vormann, Jürgen

2016-01-01

The essential mineral magnesium is involved in numerous physiological processes. Recommended dietary intake is often not met and a low magnesium status increases the risk for various diseases. Magnesium status is regulated by several magnesium transport systems either in cellular or paracellular pathways. Numerous drugs either interfere with magnesium absorption in the intestines or the reabsorption from primary urine in the kidney. Low magnesium status has been identified as a significant risk factor for several diseases, including type-2 diabetes, cardiovascular diseases, arrhythmias, as well as general muscular and neurological problems. Therefore, an adequate magnesium supply would be of special benefit to our overall health.

Aquaporins in Cardiovascular System.

PubMed

Tie, Lu; Wang, Di; Shi, Yundi; Li, Xuejun

2017-01-01

Recent studies have shown that some aquaporins (AQPs ), including AQP1, AQP4, AQP7 and AQP9, are expressed in endothelial cells, vascular smooth muscle cells and heart of cardiovascular system. These AQPs are involved in the cardiovascular function and in pathological process of related diseases, such as cerebral ischemia , congestion heart failure , hypertension and angiogenesis. Therefore, it is important to understand the accurate association between AQPs and cardiovascular system, which may provide novel approaches to prevent and treat related diseases. Here we will discuss the expression and physiological function of AQPs in cardiovascular system and summarize recent researches on AQPs related cardiovascular diseases.

DisGeNET-RDF: harnessing the innovative power of the Semantic Web to explore the genetic basis of diseases.

PubMed

Queralt-Rosinach, Núria; Piñero, Janet; Bravo, Àlex; Sanz, Ferran; Furlong, Laura I

2016-07-15

DisGeNET-RDF makes available knowledge on the genetic basis of human diseases in the Semantic Web. Gene-disease associations (GDAs) and their provenance metadata are published as human-readable and machine-processable web resources. The information on GDAs included in DisGeNET-RDF is interlinked to other biomedical databases to support the development of bioinformatics approaches for translational research through evidence-based exploitation of a rich and fully interconnected linked open data. http://rdf.disgenet.org/ support@disgenet.org. © The Author 2016. Published by Oxford University Press.

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system.

PubMed

Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

2013-03-01

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng's therapeutic effects. These include Alzheimer's disease, Parkinson's disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng.

A comprehensive review of the therapeutic and pharmacological effects of ginseng and ginsenosides in central nervous system

PubMed Central

Kim, Hee Jin; Kim, Pitna; Shin, Chan Young

2013-01-01

Ginseng is one of the most widely used herbal medicines in human. Central nervous system (CNS) diseases are most widely investigated diseases among all others in respect to the ginseng’s therapeutic effects. These include Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, depression, and many other neurological disorders including neurodevelopmental disorders. Not only the various types of diseases but also the diverse array of target pathways or molecules ginseng exerts its effect on. These range, for example, from neuroprotection to the regulation of synaptic plasticity and from regulation of neuroinflammatory processes to the regulation of neurotransmitter release, too many to mention. In general, ginseng and even a single compound of ginsenoside produce its effects on multiple sites of action, which make it an ideal candidate to develop multi-target drugs. This is most important in CNS diseases where multiple of etiological and pathological targets working together to regulate the final pathophysiology of diseases. In this review, we tried to provide comprehensive information on the pharmacological and therapeutic effects of ginseng and ginsenosides on neurodegenerative and other neurological diseases. Side by side comparison of the therapeutic effects in various neurological disorders may widen our understanding of the therapeutic potential of ginseng in CNS diseases and the possibility to develop not only symptomatic drugs but also disease modifying reagents based on ginseng. PMID:23717153

Economic value evaluation in disease management programs.

PubMed

Magnezi, Racheli; Reicher, Sima; Shani, Mordechai

2008-05-01

Chronic disease management has been a rapidly growing entity in the 21st century as a strategy for managing chronic illnesses in large populations. However, experience has shown that disease management programs have not been able to demonstrate their financial value. The objectives of disease management programs are to create quality benchmarks, such as principles and guidelines, and to establish a uniform set of metrics and a standardized methodology for evaluating them. In order to illuminate the essence of disease management and its components, as well as the complexity and the problematic nature of performing economic calculations of their profitability and value, we collected data from several reports that dealt with the economic intervention of disease management programs. The disease management economic evaluation is composed of a series of steps, including the following major categories: data/information technology, information generation, assessment/recommendations, actionable customer plans, and program assessment/reassessment. We demonstrate the elements necessary for economic analysis. Disease management is one of the most innovative tools in the managed care environment and is still in the process of being defined. Therefore, objectives should include the creation of quality measures, such as principles and guidelines, and the establishment of a uniform set of metrics and a standardized methodology for evaluating them.

Gene-environment interactions in the aetiology of systemic lupus erythematosus.

PubMed

Jönsen, Andreas; Bengtsson, Anders A; Nived, Ola; Truedsson, Lennart; Sturfelt, Gunnar

2007-12-01

Systemic lupus erythematosus (SLE) is a disease that displays a multitude of symptoms and a vast array of autoantibodies. The disease course may vary substantially between patients. The current understanding of SLE aetiology includes environmental factors acting on a genetically prone individual during an undetermined time period resulting in autoimmunity and finally surpassing that individual's disease threshold. Genetic differences and environmental factors may interact specifically in the pathogenetic processes and may influence disease development and modify the disease course. Identification of these factors and their interactions in the pathogenesis of SLE is vital in understanding the disease and may contribute to identify new treatment targets and perhaps also aid in disease prevention. However, there are several problems that need to be overcome, such as the protracted time frame of environmental influence, time dependent epigenetic alterations and the possibility that different pathogenetic pathways may result in a similar disease phenotype. This is mirrored by the relatively few studies that suggest specific gene-environment interactions. These include an association between SLE diagnosis and glutation S-transferase gene variants combined with occupational sun exposure as well as variants of the N-acetyl transferase gene in combination with either aromatic amine exposure or hydralazine. With increased knowledge on SLE pathogenesis, the role of environmental factors and their genetic interactions may be further elucidated.

The relationship between swainsonine containing plants and endophytic fungi

USDA-ARS?s Scientific Manuscript database

Swainsonine, an indolizidine alkaloid with significant physiological activity, is an a-mannosidase and mannosidase II inhibitor that alters glycoprotein processing and causes lysosomal storage disease. Swainsonine is present in a number of plant families worldwide including the Convolvulaceae, Faba...

RELATIONSHIP BETWEEN INDUCED OXIDENT GENERATION AND ASTHMA SEVERITY

EPA Science Inventory

The role of oxygen radicals is implicated in many disease processes, including asthma. There is evidence that elevated oxidant status is associated with airway hyper responsiveness, however it is less clear whether increased levels of circulating reactive oxygen species are assoc...

Establishment of an innovative specialist cardiac indigenous outreach service in rural and remote Queensland.

PubMed

Tibby, David; Corpus, Rohan; Walters, Darren L

2010-01-01

Cardiovascular diseases are the leading cause of mortality in Indigenous Australians. Indigneous Australians present at a younger age and have a greater incidence of cardiac risk including smoking and diabetes than non-Indigenous Australians. Access to specialist health services is an important determinant of health care outcomes for these patients. We describe an innovative and successful for model for providing Outreach Cardiac Specialist services to Indigenous communities in rural and remote locations. The approach involves a step-wise process of a) community engagement, b) delivering recovery interventions to improve health outcomes, c) building community capacity to self manage chronic illness and promoting health and well being with the aim of d) community self governance of chronic disease and health promotion. Key elements to this process are community participation in the program, disease self-management led by local health care workers, open access that is all-inclusive utilising community-generated referral, and the translation of scientific knowledge of disease processes into community understanding and making culturally relevant connections. Specialist cardiac services and point of care diagnostics have been provided to 18 sites across rural and remote Queensland. More than 1400 episodes of care have been provided to Indigenous Australians with rheumatic heart disease, ischaemic heart disease and congenital heart conditions. Traditional values can work harmoniously with an inclusive medical approach in this relational model. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

From COPD epidemiology to studies of pathophysiological disease mechanisms: challenges with regard to study design and recruitment process: Respiratory and Cardiovascular Effects in COPD (KOLIN).

PubMed

Lindberg, Anne; Linder, Robert; Backman, Helena; Eriksson Ström, Jonas; Frølich, Andreas; Nilsson, Ulf; Rönmark, Eva; Johansson Strandkvist, Viktor; Behndig, Annelie F; Blomberg, Anders

2017-01-01

Background : Chronic obstructive pulmonary disease (COPD) is a largely underdiagnosed disease including several phenotypes. In this report, the design of a study intending to evaluate the pathophysiological mechanism in COPD in relation to the specific phenotypes non-rapid and rapid decline in lung function is described together with the recruitment process of the study population derived from a population based study. Method : The OLIN COPD study includes a population-based COPD cohort and referents without COPD identified in 2002-04 ( n  = 1986), and thereafter followed annually since 2005. Lung function decline was estimated from baseline in 2002-2004 to 2010 (first recruitment phase) or to 2012/2013 (second recruitment phase). Individuals who met the predefined criteria for the following four groups were identified; group A) COPD grade 2-3 with rapid decline in FEV 1 and group B) COPD grade 2-3 without rapid decline in FEV 1 (≥60 and ≤30 ml/year, respectively), group C) ever-smokers, and group D) non-smokers with normal lung function. Groups A-C included ever-smokers with >10 pack years. The intention was to recruit 15 subjects in each of the groups A-D. Results : From the database groups A-D were identified; group A n  = 37, group B n  = 29, group C n  = 41, and group D n  = 55. Fifteen subjects were recruited from groups C and D, while this goal was not reached in the groups A ( n  = 12) and B ( n  = 10). The most common reasons for excluding individuals identified as A or B were comorbidities contraindicating bronchoscopy, or inflammatory diseases/immune suppressive medication expected to affect the outcome. Conclusion : The study is expected to generate important results regarding pathophysiological mechanisms associated with rate of decline in lung function among subjects with COPD and the in-detail described recruitment process, including reasons for non-participation, is a strength when interpreting the results in forthcoming studies.

Contribution of inflammatory pathways to Fabry disease pathogenesis.

PubMed

Rozenfeld, Paula; Feriozzi, Sandro

2017-11-01

Lysosomal storage diseases are usually considered to be pathologies in which the passive deposition of unwanted materials leads to functional changes in lysosomes. Lysosomal deposition of unmetabolized glycolipid substrates stimulates the activation of pathogenic cascades, including immunological processes, and particularly the activation of inflammation. In lysosomal storage diseases, the inflammatory response is continuously being activated because the stimulus cannot be eliminated. Consequently, inflammation becomes a chronic process. Lysosomes play a role in many steps of the immune response. Leukocyte perturbation and over-expression of immune molecules have been reported in Fabry disease. Innate immunity is activated by signals originating from dendritic cells via interactions between toll-like receptors and globotriaosylceramide (Gb3) and/or globotriaosylsphingosine (lyso-Gb3). Evidence indicates that these glycolipids can activate toll-like receptors, thus triggering inflammation and fibrosis cascades. In the kidney, Gb3 deposition is associated with the increased release of transforming growth factor beta and with epithelial-to-mesenchymal cell transition, leading to the over-expression of pro-fibrotic molecules and to renal fibrosis. Interstitial fibrosis is also a typical feature of heart involvement in Fabry disease. Endomyocardial biopsies show infiltration of lymphocytes and macrophages, suggesting a role for inflammation in causing tissue damage. Inflammation is present in all tissues and may be associated with other potentially pathologic processes such as apoptosis, impaired autophagy, and increases in pro-oxidative molecules, which could all contribute synergistically to tissue damage. In Fabry disease, the activation of chronic inflammation over time leads to organ damage. Therefore, enzyme replacement therapy must be started early, before this process becomes irreversible. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes

PubMed Central

Justice, Jamie; Miller, Jordan D.; Newman, John C.; Hashmi, Shahrukh K.; Halter, Jeffrey; Austad, Steve N.; Barzilai, Nir

2016-01-01

Therapies targeted at fundamental processes of aging may hold great promise for enhancing the health of a wide population by delaying or preventing a range of age-related diseases and conditions—a concept dubbed the “geroscience hypothesis.” Early, proof-of-concept clinical trials will be a key step in the translation of therapies emerging from model organism and preclinical studies into clinical practice. This article summarizes the outcomes of an international meeting partly funded through the NIH R24 Geroscience Network, whose purpose was to generate concepts and frameworks for early, proof-of-concept clinical trials for therapeutic interventions that target fundamental processes of aging. The goals of proof-of-concept trials include generating preliminary signals of efficacy in an aging-related disease or outcome that will reduce the risk of conducting larger trials, contributing data and biological samples to support larger-scale research by strategic networks, and furthering a dialogue with regulatory agencies on appropriate registration indications. We describe three frameworks for proof-of-concept trials that target age-related chronic diseases, geriatric syndromes, or resilience to stressors. We propose strategic infrastructure and shared resources that could accelerate development of therapies that target fundamental aging processes. PMID:27535966

Abnormal Thiamine-Dependent Processes in Alzheimer’s Disease. Lessons from Diabetes

PubMed Central

Gibson, Gary E.; Hirsch, Joseph A.; Cirio, Rosanna T.; Jordan, Barry D.; Fonzetti, Pasquale; Elder, Jessica

2013-01-01

Reduced glucose metabolism is an invariant feature of Alzheimer’s Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. PMID:22982063

Coexpression network based on natural variation in human gene expression reveals gene interactions and functions

PubMed Central

Nayak, Renuka R.; Kearns, Michael; Spielman, Richard S.; Cheung, Vivian G.

2009-01-01

Genes interact in networks to orchestrate cellular processes. Analysis of these networks provides insights into gene interactions and functions. Here, we took advantage of normal variation in human gene expression to infer gene networks, which we constructed using correlations in expression levels of more than 8.5 million gene pairs in immortalized B cells from three independent samples. The resulting networks allowed us to identify biological processes and gene functions. Among the biological pathways, we found processes such as translation and glycolysis that co-occur in the same subnetworks. We predicted the functions of poorly characterized genes, including CHCHD2 and TMEM111, and provided experimental evidence that TMEM111 is part of the endoplasmic reticulum-associated secretory pathway. We also found that IFIH1, a susceptibility gene of type 1 diabetes, interacts with YES1, which plays a role in glucose transport. Furthermore, genes that predispose to the same diseases are clustered nonrandomly in the coexpression network, suggesting that networks can provide candidate genes that influence disease susceptibility. Therefore, our analysis of gene coexpression networks offers information on the role of human genes in normal and disease processes. PMID:19797678

The Inescapable Influence of Noncoding RNAs in Cancer

PubMed Central

Adams, Brian D.; Anastasiadou, Eleni; Esteller, Manel; He, Lin; Slack, Frank J.

2015-01-01

This report summarizes information presented at the 2015 Keystone Symposium on “MicroRNAs and Noncoding RNAs in Cancer”. Nearly two decades after the discovery of the first microRNA (miRNA), the role of noncoding RNAs in developmental processes and the mechanisms behind their dysregulation in cancer has been steadily elucidated. Excitingly, miRNAs have begun making their way into the clinic to combat disease such a hepatitis C, and various forms of cancer. Therefore, at this Keystone meeting novel findings were presented that enhance our view on how small and long noncoding RNAs control developmental timing and oncogenic processes. Recurring themes included, 1) how miRNAs can be differentially processed, degraded, and regulated by ribonucleoprotein (RNP) complexes, 2) how particular miRNA genetic networks that control developmental process, when disrupted, can result in cancer disease, 3) the technologies available to therapeutically deliver RNA to combat diseases such as cancer, and 4) the elucidation of the mechanism of actions for long noncoding RNAs, currently a poorly understood class of noncoding RNA. During the meeting there was an emphasis on presenting unpublished findings, and the breadth of topics covered reflected how inescapable the influence of noncoding RNAs are in development and cancer. PMID:26567137

Antibodies and antimatter: the resurgence of immuno-PET.

PubMed

Wu, Anna M

2009-01-01

The completion of the human genome, coupled with parallel major research efforts in proteomics and systems biology, has led to a flood of information on the roles of individual genes and proteins in normal physiologic processes and their disruptions in disease. In practical terms, this information has opened the door to increasingly targeted therapies as specific molecular markers are identified and validated. The ongoing transition from empiric to molecular medicine has engendered a need for corresponding molecular diagnostics, including noninvasive molecular imaging. Convergence of knowledge regarding key biomarkers that define normal biologic processes and disease with protein and imaging technology makes this an opportune time to revisit the combination of antibodies and PET, or immuno-PET.

Specificity and disease in the ubiquitin system

PubMed Central

Chaugule, Viduth K.; Walden, Helen

2016-01-01

Post-translational modification (PTM) of proteins by ubiquitination is an essential cellular regulatory process. Such regulation drives the cell cycle and cell division, signalling and secretory pathways, DNA replication and repair processes and protein quality control and degradation pathways. A huge range of ubiquitin signals can be generated depending on the specificity and catalytic activity of the enzymes required for attachment of ubiquitin to a given target. As a consequence of its importance to eukaryotic life, dysfunction in the ubiquitin system leads to many disease states, including cancers and neurodegeneration. This review takes a retrospective look at our progress in understanding the molecular mechanisms that govern the specificity of ubiquitin conjugation. PMID:26862208

Chronic inflammation is etiology of extrinsic aging.

PubMed

Thornfeldt, Carl R

2008-03-01

Skin care regimens using active ingredients that are recommended by physicians who treat mucocutaneous conditions including aging should become more focused on reversing and preventing chronic inflammation. This adjustment of therapeutic and preventive strategies is necessary because chronic inflammation appears strongly linked to many preventable and treatable skin diseases and conditions such as visible skin aging. Mucocutaneous inflammation as the final common pathway of many systemic and mucocutaneous diseases including extrinsic aging has been established at the molecular and cellular levels. The corollary to this strategy includes inhibition of primary activators of mucocutaneous inflammation such as stratum corneum permeability barrier disruption, blocking any pro-inflammatory environmental insult such as ultraviolet radiation, and quenching tissue responses to these insults. This review will present the scientific rationale substantiating the conclusion that chronic inflammation is the common denominator in many mucocutaneous pathophysiologic processes including extrinsic skin aging.

[Erythema nodosum during the course of idiopathic granulomatous mastitis].

PubMed

Fahmy, J; Halabi-Tawil, M; Bagot, M; Tournant, B; Petit, A

2015-01-01

Idiopathic granulomatous mastitis (IGM) is a benign, aseptic inflammatory disease of unknown origin, which must be distinguished from tumoral and infectious processes that affect the breast, including tuberculosis. IGM is a rare cause of erythema nodosum, but it is useful for dermatologists to be aware of this association. A 32-year-old nulliparous woman presented with erythema nodosum, arthralgia and fever. On examination, she had a firm and painful mass of 5cm in the right breast with retraction and axillary adenopathy. The breast lump developed gradually over the preceding 4 months. Although two biopsies showed no evidence of atypical cells, inflammatory areas and a granulomatous process were seen. Culture of breast tissue for mycobacteria was negative. A diagnostic of idiopathic granulomatous mastitis was made. Systemic corticosteroids led to a reduction in size of the mass, but relapse occurred in the contralateral breast on dose-reduction of the corticosteroids. IGM is a rare disease of unknown aetiology. Diagnosis is based on characteristic histological features and exclusion of other granulomatous diseases. Extra-mammary signs are rare and include erythema nodosum, arthralgia and episcleritis. Management is poorly codified. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Nicholas Metropolis Award Talk for Outstanding Doctoral Thesis Work in Computational Physics: Computational biophysics and multiscale modeling of blood cells and blood flow in health and disease

NASA Astrophysics Data System (ADS)

Fedosov, Dmitry

2011-03-01

Computational biophysics is a large and rapidly growing area of computational physics. In this talk, we will focus on a number of biophysical problems related to blood cells and blood flow in health and disease. Blood flow plays a fundamental role in a wide range of physiological processes and pathologies in the organism. To understand and, if necessary, manipulate the course of these processes it is essential to investigate blood flow under realistic conditions including deformability of blood cells, their interactions, and behavior in the complex microvascular network. Using a multiscale cell model we are able to accurately capture red blood cell mechanics, rheology, and dynamics in agreement with a number of single cell experiments. Further, this validated model yields accurate predictions of the blood rheological properties, cell migration, cell-free layer, and hemodynamic resistance in microvessels. In addition, we investigate blood related changes in malaria, which include a considerable stiffening of red blood cells and their cytoadherence to endothelium. For these biophysical problems computational modeling is able to provide new physical insights and capabilities for quantitative predictions of blood flow in health and disease.

Functional O-GlcNAc modifications: Implications in molecular regulation and pathophysiology

PubMed Central

Wells, Lance

2016-01-01

O-linked β-N-acetylglucosamine (O-GlcNAc) is a regulatory post-translational modification of intracellular proteins. The dynamic and inducible cycling of the modification is governed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in response to UDP-GlcNAc levels in the hexosamine biosynthetic pathway (HBP). Due to its reliance on glucose flux and substrate availability, a major focus in the field has been on how O-GlcNAc contributes to metabolic disease. For years this post-translational modification has been known to modify thousands of proteins implicated in various disorders, but direct functional connections have until recently remained elusive. New research is beginning to reveal the specific mechanisms through which O-GlcNAc influences cell dynamics and disease pathology including clear examples of O-GlcNAc modification at a specific site on a given protein altering its biological functions. The following review intends to focus primarily on studies in the last half decade linking O-GlcNAc modification of proteins with chromatin-directed gene regulation, developmental processes, and several metabolically related disorders including Alzheimer’s, heart disease and cancer. These studies illustrate the emerging importance of this post-translational modification in biological processes and multiple pathophysiologies. PMID:24524620

Recruitment of subjects into clinical trials for Alzheimer disease.

PubMed

Knebl, Janice A; Patki, Deepti

2010-09-01

Alzheimer disease is a devastating neurodegenerative disorder affecting millions of Americans. It reduces the ability of the individual to remain independent, places a burden on caregivers, and substantially increases healthcare costs. New treatments are being tested in numerous clinical trials with the goal of preventing or delaying the onset of Alzheimer disease, slowing or modifying the disease's course, or finding a cure for patients with the disease. Alzheimer disease research can successfully proceed only if individuals who have this illness are willing to participate in clinical trials. However, recruitment and retention of subjects in clinical trials for Alzheimer disease is a challenging task. Furthermore, because of reductions in decision-making capacities of individuals with Alzheimer disease, clinical trials also need to involve caregivers. The present article delineates unique hurdles encountered in the recruitment process for Alzheimer disease clinical trials. The article also identifies strategies for effective recruitment of subjects in Alzheimer disease clinical trials, including guidelines to help principal investigators and clinical research coordinators reach recruitment goals.

Using voluntary reports from physicians to learn from diagnostic errors in emergency medicine.

PubMed

Okafor, Nnaemeka; Payne, Velma L; Chathampally, Yashwant; Miller, Sara; Doshi, Pratik; Singh, Hardeep

2016-04-01

Diagnostic errors are common in the emergency department (ED), but few studies have comprehensively evaluated their types and origins. We analysed incidents reported by ED physicians to determine disease conditions, contributory factors and patient harm associated with ED-related diagnostic errors. Between 1 March 2009 and 31 December 2013, ED physicians reported 509 incidents using a department-specific voluntary incident-reporting system that we implemented at two large academic hospital-affiliated EDs. For this study, we analysed 209 incidents related to diagnosis. A quality assurance team led by an ED physician champion reviewed each incident and interviewed physicians when necessary to confirm the presence/absence of diagnostic error and to determine the contributory factors. We generated descriptive statistics quantifying disease conditions involved, contributory factors and patient harm from errors. Among the 209 incidents, we identified 214 diagnostic errors associated with 65 unique diseases/conditions, including sepsis (9.6%), acute coronary syndrome (9.1%), fractures (8.6%) and vascular injuries (8.6%). Contributory factors included cognitive (n=317), system related (n=192) and non-remedial (n=106). Cognitive factors included faulty information verification (41.3%) and faulty information processing (30.6%) whereas system factors included high workload (34.4%) and inefficient ED processes (40.1%). Non-remediable factors included atypical presentation (31.3%) and the patients' inability to provide a history (31.3%). Most errors (75%) involved multiple factors. Major harm was associated with 34/209 (16.3%) of reported incidents. Most diagnostic errors in ED appeared to relate to common disease conditions. While sustaining diagnostic error reporting programmes might be challenging, our analysis reveals the potential value of such systems in identifying targets for improving patient safety in the ED. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Neural Mechanisms of Meditative Practices: Novel Approaches for Healthy Aging.

PubMed

Acevedo, Bianca P; Pospos, Sarah; Lavretsky, Helen

2016-01-01

Meditation has been shown to have physical, cognitive, and psychological health benefits that can be used to promote healthy aging. However, the common and specific mechanisms of response remain elusive due to the diverse nature of mind-body practices. In this review, we aim to compare the neural circuits implicated in focused-attention meditative practices that focus on present-moment awareness to those involved in active-type meditative practices (e.g., yoga) that combine movement, including chanting, with breath practices and meditation. Recent meta-analyses and individual studies demonstrated common brain effects for attention-based meditative practices and active-based meditations in areas involved in reward processing and learning, attention and memory, awareness and sensory integration, and self-referential processing and emotional control, while deactivation was seen in the amygdala, an area implicated in emotion processing. Unique effects for mindfulness practices were found in brain regions involved in body awareness, attention, and the integration of emotion and sensory processing. Effects specific to active-based meditations appeared in brain areas involved in self-control, social cognition, language, speech, tactile stimulation, sensorimotor integration, and motor function. This review suggests that mind-body practices can target different brain systems that are involved in the regulation of attention, emotional control, mood, and executive cognition that can be used to treat or prevent mood and cognitive disorders of aging, such as depression and caregiver stress, or serve as "brain fitness" exercise. Benefits may include improving brain functional connectivity in brain systems that generally degenerate with Alzheimer's disease, Parkinson's disease, and other aging-related diseases.

Disease management programs for type 2 diabetes in Germany: a systematic literature review evaluating effectiveness.

PubMed

Fuchs, Sabine; Henschke, Cornelia; Blümel, Miriam; Busse, Reinhard

2014-06-27

Disease management programs (DMPs) are intended to improve the care of persons with chronic diseases. Despite numerous studies there is no unequivocal evidence about the effectiveness of DMPs in Germany. We conducted a systematic literature review in the MEDLINE, EMBASE, Cochrane Library, and CCMed databases. Our analysis included all controlled studies in which patients with type 2 diabetes enrolled in a DMP were compared to type 2 diabetes patients receiving routine care with respect to process, outcome, and economic parameters. The 9 studies included in the analysis were highly divergent with respect to their characteristics and the process and outcome parameters studied in each. No study had data beyond the year 2008. In 3 publications, the DMP patients had a lower mortality than the control patients (2.3%, 11.3%, and 7.17% versus 4.7%, 14.4%, and 14.72%). In 2 publications, DMP participation was found to be associated with a mean survival time of 1044.94 (± 189.87) days, as against 985.02 (± 264.68) in the control group. No consistent effect was seen with respect to morbidity, quality of life, or economic parameters. 7 publications from 5 studies revealed positive effects on process parameters for DMP participants. The observed beneficial trends with respect to mortality and survival time, as well as improvements in process parameters, indicate that DMPs can, in fact, improve the care of patients with diabetes. Further evaluation is needed, because some changes in outcome parameters (an important indicator of the quality of care) may only be observable over a longer period of time.

Research of processes of reception and analysis of dynamic digital medical images in hardware/software complexes used for diagnostics and treatment of cardiovascular diseases

NASA Astrophysics Data System (ADS)

Karmazikov, Y. V.; Fainberg, E. M.

2005-06-01

Work with DICOM compatible equipment integrated into hardware and software systems for medical purposes has been considered. Structures of process of reception and translormation of the data are resulted by the example of digital rentgenography and angiography systems, included in hardware-software complex DIMOL-IK. Algorithms of reception and the analysis of the data are offered. Questions of the further processing and storage of the received data are considered.

Mitochondrial Approaches to Protect Against Cardiac Ischemia and Reperfusion Injury

PubMed Central

Camara, Amadou K. S.; Bienengraeber, Martin; Stowe, David F.

2011-01-01

The mitochondrion is a vital component in cellular energy metabolism and intracellular signaling processes. Mitochondria are involved in a myriad of complex signaling cascades regulating cell death vs. survival. Importantly, mitochondrial dysfunction and the resulting oxidative and nitrosative stress are central in the pathogenesis of numerous human maladies including cardiovascular diseases, neurodegenerative diseases, diabetes, and retinal diseases, many of which are related. This review will examine the emerging understanding of the role of mitochondria in the etiology and progression of cardiovascular diseases and will explore potential therapeutic benefits of targeting the organelle in attenuating the disease process. Indeed, recent advances in mitochondrial biology have led to selective targeting of drugs designed to modulate or manipulate mitochondrial function, to the use of light therapy directed to the mitochondrial function, and to modification of the mitochondrial genome for potential therapeutic benefit. The approach to rationally treat mitochondrial dysfunction could lead to more effective interventions in cardiovascular diseases that to date have remained elusive. The central premise of this review is that if mitochondrial abnormalities contribute to the etiology of cardiovascular diseases (e.g., ischemic heart disease), alleviating the mitochondrial dysfunction will contribute to mitigating the severity or progression of the disease. To this end, this review will provide an overview of our current understanding of mitochondria function in cardiovascular diseases as well as the potential role for targeting mitochondria with potential drugs or other interventions that lead to protection against cell injury. PMID:21559063

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease.

PubMed

Marwarha, Gurdeep; Ghribi, Othman

2017-01-01

NF-κB is a ubiquitous transcription factor that was discovered three decades ago. Since its discovery, this protein complex has been implicated in numerous physiological and pathophysiological processes such as synaptic plasticity, learning and memory, inflammation, insulin resistance, and oxidative stress among other factors that are intricately involved and dysregulated in Alzheimer's disease (AD). We embarked on a methodical and an objective review of contemporary literature to integrate the indispensable physiological functions of NF-κB in neuronal phsyiology with the undesirable pathophysiological attributes of NF-κB in the etiopathogenesis of Alzheimer's disease. In our approach, we first introduced Alzheimer's disease and subsequently highlighted the multifaceted roles of NF-κB in the biological processes altered in the progression of Alzheimer's disease including synaptic transmission, synaptic plasticity, learning, and memory, neuronal survival and apoptosis, adult neurogenesis, regulation of neural processes and structural plasticity, inflammation, and Amyloid-β production and toxicity. Our comprehensive review highlights and dissects the physiological role of NF-κB from its pathological role in the brain and delineates both, its beneficial as well as deleterious, role in the etiopathogenesis of Alzheimer's disease. In light of our understanding of the duality of the role of NF-κB in the pathogenesis of Alzheimer's disease, further studies are warranted to dissect and understand the basis of the dichotomous effects of NF-κB, so that certain selective benevolent and benign attributes of NF-κB can be spared while targeting its deleterious attributes and facets that are integral in the pathogenesis of Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Review of the Pathophysiology and Treatment of Psychosis in Parkinson’s Disease

PubMed Central

Zahodne, Laura B.; Fernandez, Hubert H.

2011-01-01

Psychotic symptoms in Parkinson’s disease (PD) are relatively common, and in addition to being a disturbance to patients’ daily lives, they have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past fifteen years, from an initial interpretation of symptoms as dopaminergic drug side effects to the current view of a complex interplay of extrinsic and disease-related factors. The present article reviews the unique clinical features of psychosis as expressed in PD, associated risk factors, and current theories behind its pathogenesis, including medications, visual processing deficits, sleep disturbances, genetics, and neurochemical and structural abnormalities. Finally, we review both traditional and emergent management strategies for PD psychosis, including antipsychotic agents, cholinesterase inhibitors, electroconvulsive therapy (ECT), and other pharmacological and psychological interventions. PMID:18665659

Possible Role of Common Spices as a Preventive and Therapeutic Agent for Alzheimer's Disease.

PubMed

Mirmosayyeb, Omid; Tanhaei, Amirpouya; Sohrabi, Hamid R; Martins, Ralph N; Tanhaei, Mana; Najafi, Mohammad Amin; Safaei, Ali; Meamar, Rokhsareh

2017-01-01

For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid β aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed.

Possible Role of Common Spices as a Preventive and Therapeutic Agent for Alzheimer's Disease

PubMed Central

Mirmosayyeb, Omid; Tanhaei, Amirpouya; Sohrabi, Hamid R.; Martins, Ralph N.; Tanhaei, Mana; Najafi, Mohammad Amin; Safaei, Ali; Meamar, Rokhsareh

2017-01-01

For centuries, spices have been consumed as food additives or medicinal agents. However, there is increasing evidence indicating the plant-based foods in regular diet may lower the risk of neurodegenerative diseases including Alzheimer disease. Spices, as one of the most commonly used plant-based food additives may provide more than just flavors, but as agents that may prevent or even halt neurodegenerative processes associated with aging. In this article, we review the role and application of five commonly used dietary spices including saffron turmeric, pepper family, zingiber, and cinnamon. Besides suppressing inflammatory pathways, these spices may act as antioxidant and inhibit acetyl cholinesterase and amyloid β aggregation. We summarized how spice-derived nutraceuticals mediate such different effects and what their molecular targets might be. Finally, some directions for future research are briefly discussed. PMID:28250905

Matrix Metalloproteinases as Regulators of Periodontal Inflammation

PubMed Central

Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández

2017-01-01

Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation. PMID:28218665

Alternative splicing in plant immunity.

PubMed

Yang, Shengming; Tang, Fang; Zhu, Hongyan

2014-06-10

Alternative splicing (AS) occurs widely in plants and can provide the main source of transcriptome and proteome diversity in an organism. AS functions in a range of physiological processes, including plant disease resistance, but its biological roles and functional mechanisms remain poorly understood. Many plant disease resistance (R) genes undergo AS, and several R genes require alternatively spliced transcripts to produce R proteins that can specifically recognize pathogen invasion. In the finely-tuned process of R protein activation, the truncated isoforms generated by AS may participate in plant disease resistance either by suppressing the negative regulation of initiation of immunity, or by directly engaging in effector-triggered signaling. Although emerging research has shown the functional significance of AS in plant biotic stress responses, many aspects of this topic remain to be understood. Several interesting issues surrounding the AS of R genes, especially regarding its functional roles and regulation, will require innovative techniques and additional research to unravel.

Matrix Metalloproteinases as Regulators of Periodontal Inflammation.

PubMed

Franco, Cavalla; Patricia, Hernández-Ríos; Timo, Sorsa; Claudia, Biguetti; Marcela, Hernández

2017-02-17

Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the 'protease web' is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules-such as cytokines, chemokines, and growth factors, among others-regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation.

Review article: mitogen-activated protein kinases in chronic intestinal inflammation - targeting ancient pathways to treat modern diseases.

PubMed

Waetzig, G H; Schreiber, S

2003-07-01

Conventional treatment of chronic inflammatory disorders, including inflammatory bowel diseases, employs broad-range anti-inflammatory drugs. In order to reduce the side-effects and increase the efficacy of treatment, several strategies have been developed in the last decade to interfere with intercellular and intracellular inflammatory signalling processes. The highly conserved mitogen-activated protein kinase pathways regulate most cellular processes, particularly defence mechanisms such as stress reactions and inflammation. In this review, we provide an overview of the current knowledge of the specificity and interconnection of mitogen-activated protein kinase pathways, their functions in the gut immune system and published and ongoing studies on the role of mitogen-activated protein kinases in inflammatory bowel disease. The development of mitogen-activated protein kinase inhibitors and their use for the therapy of inflammatory disorders is a paradigm of the successful bridging of the gap between basic research and clinical practice.

Experiences of living with motor neurone disease: a review of qualitative research.

PubMed

Sakellariou, Dikaios; Boniface, Gail; Brown, Paul

2013-10-01

This review sought to answer the question "what is known about people's experiences of living with MND?". The review followed the guidelines of the Centre of Reviews and Dissemination. Twenty articles met the inclusion criteria and their results were analysed thematically. Data were managed and coded using the software package NVIVO and the analysis was performed in two stages, with the first stage aiming to develop descriptive themes offering an overview of the included data. During the second stage, analytical themes were developed with the explicit aim to answer the review question. The themes that emerged point to the following: (a) people with motor neurone disease (MND) develop experiential knowledge that helps them to live with the disease and (b) while people with MND believe they do not have any control over the disease, they try to have control over their lives through active choices, e.g. how and when to use adaptive equipment. This review highlights the decision-making and knowledge generating processes used by people with MND. Further research is required to explore these processes and their implications for the care of people with MND. Decision-making process by MND patients regarding their care is complex and takes into account the social elements of the disease as well as the medical. Exploring the practical knowledge that patients develop can offer insights on appropriate care for MND patients.

Alive and Well? Exploring Disease by Studying Lifespan

PubMed Central

Brett, Jamie O.; Rando, Thomas A.

2014-01-01

A common concept in aging research is that chronological age is the most important risk factor for the development of diverse diseases, including degenerative diseases and cancers. The mechanistic link between the aging process and disease pathogenesis, however, is still enigmatic. Nevertheless, measurement of lifespan, as a surrogate for biological aging, remains among the most frequently used assays in aging research. In this review, we examine the connection between “normal aging” and age-related disease from the point of view that they form a continuum of aging phenotypes. This notion of common mechanisms gives rise to the converse postulate that diseases may be risk factors for accelerated aging. We explore the advantages and caveats associated with using lifespan as a metric to understand cell and tissue aging, focusing on the elucidation of molecular mechanisms and potential therapies for age-related diseases. PMID:25005743

Disease management improves end-stage renal disease outcomes.

PubMed

Sands, Jeffrey J

2006-01-01

Renal disease management organizations have reported achieving significant decreases in mortality and hospitalization in conjunction with cost savings, improved patient satisfaction and quality of life. Disease management organizations strive to fill existing gaps in care delivery through the standardized use of risk assessment, predictive modeling, evidence-based guidelines, and process and outcomes measurement. Patient self-management education and the provision of individual nurse care managers are also key program components. As we more fully measure clinical outcomes and total healthcare costs, including payments from all insurance and government entities, pharmacy costs and out of pocket expenditures, the full implications of disease management can be better defined. The results of this analysis will have a profound influence on United States healthcare policy. At present current data suggest that the promise of disease management, improved care at reduced cost, can and is being realized in end-stage renal disease. Copyright 2006 S. Karger AG, Basel.

Oral lichenoid lesions: distinguishing the benign from the deadly.

PubMed

Müller, Susan

2017-01-01

Oral lichen planus is a chronic inflammatory disease of unknown etiology or pathogenesis with varied disease severity that waxes and wanes over a long period of time. Although a common oral mucosal disease, accurate diagnosis is often challenging due to the overlapping clinical and histopathological features of oral lichen planus and other mucosal diseases. Other immune-mediated mucocutaneous diseases can exhibit lichenoid features including mucous membrane pemphigoid, chronic graft-versus-host disease, and discoid lupus erythematosus. Reactive changes to dental materials or to systemic medications can mimic oral lichen planus both clinically and histologically. In these situations the clinical presentation can be useful, as oral lichen planus presents as a multifocal process and is usually symmetrical and bilateral. Dysplasia of the oral cavity can exhibit a lichenoid histology, which may mask the potentially premalignant features. Proliferative verrucous leukoplakia, an unusual clinical disease, can often mimic oral lichen planus clinically, requiring careful correlation of the clinical and pathologic features.

Acute pancreatitis during sickle cell vaso-occlusive painful crisis.

PubMed

Ahmed, Shahid; Siddiqui, Anita K; Siddiqui, Rina K; Kimpo, Miriam; Russo, Linda; Mattana, Joseph

2003-07-01

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease. Copyright 2003 Wiley-Liss, Inc.

Language impairment in Alzheimer’s disease and benefits of acetylcholinesterase inhibitors

PubMed Central

Ferris, Steven H; Farlow, Martin

2013-01-01

Alzheimer’s disease is characterized by progressively worsening deficits in several cognitive domains, including language. Language impairment in Alzheimer’s disease primarily occurs because of decline in semantic and pragmatic levels of language processing. Given the centrality of language to cognitive function, a number of language-specific scales have been developed to assess language deficits throughout progression of the disease and to evaluate the effects of pharmacotherapy on language function. Trials of acetylcholinesterase inhibitors, used for the treatment of clinical symptoms of Alzheimer’s disease, have generally focused on overall cognitive effects. However, in the current report, we review data indicating specific beneficial effects of acetylcholinesterase inhibitors on language abilities in patients with Alzheimer’s disease, with a particular focus on outcomes among patients in the moderate and severe disease stages, during which communication is at risk and preservation is particularly important. PMID:23946647

Natural products as modulator of autophagy with potential clinical prospects.

PubMed

Wang, Peiqi; Zhu, Lingjuan; Sun, Dejuan; Gan, Feihong; Gao, Suyu; Yin, Yuanyuan; Chen, Lixia

2017-03-01

Natural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in autophagy modulation, either inducing or inhibiting autophagy, through multiple signaling pathways and transcriptional regulators. In this review, we summarize natural compounds regulating autophagy in multifarious diseases including cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases, and immune diseases, hoping to inspire further investigation of the underlying mechanisms of natural compounds and to facilitate their clinical use for multiple human diseases.

Automated data processing of { 1H-decoupled} 13C MR spectra acquired from human brain in vivo

NASA Astrophysics Data System (ADS)

Shic, Frederick; Ross, Brian

2003-06-01

In clinical 13C infusion studies, broadband excitation of 200 ppm of the human brain yields 13C MR spectra with a time resolution of 2-5 min and generates up to 2000 metabolite peaks over 2 h. We describe a fast, automated, observer-independent technique for processing { 1H-decoupled} 13C spectra. Quantified 13C spectroscopic signals, before and after the administration of [1- 13C]glucose and/or [1- 13C]acetate in human subjects are determined. Stepwise improvements of data processing are illustrated by examples of normal and pathological results. Variation in analysis of individual 13C resonances ranged between 2 and 14%. Using this method it is possible to reliably identify subtle metabolic effects of brain disease including Alzheimer's disease and epilepsy.

Mitochondrial Dynamics in Mitochondrial Diseases

PubMed Central

Suárez-Rivero, Juan M.; Villanueva-Paz, Marina; de la Cruz-Ojeda, Patricia; de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Sánchez-Alcázar, José A.

2016-01-01

Mitochondria are very versatile organelles in continuous fusion and fission processes in response to various cellular signals. Mitochondrial dynamics, including mitochondrial fission/fusion, movements and turnover, are essential for the mitochondrial network quality control. Alterations in mitochondrial dynamics can cause neuropathies such as Charcot-Marie-Tooth disease in which mitochondrial fusion and transport are impaired, or dominant optic atrophy which is caused by a reduced mitochondrial fusion. On the other hand, mitochondrial dysfunction in primary mitochondrial diseases promotes reactive oxygen species production that impairs its own function and dynamics, causing a continuous vicious cycle that aggravates the pathological phenotype. Mitochondrial dynamics provides a new way to understand the pathophysiology of mitochondrial disorders and other diseases related to mitochondria dysfunction such as diabetes, heart failure, or Hungtinton’s disease. The knowledge about mitochondrial dynamics also offers new therapeutics targets in mitochondrial diseases. PMID:28933354

Impact of Air Pollutants on Oxidative Stress in Common Autophagy-Mediated Aging Diseases

PubMed Central

Numan, Mohamed Saber; Brown, Jacques P.; Michou, Laëtitia

2015-01-01

Atmospheric pollution-induced cellular oxidative stress is probably one of the pathogenic mechanisms involved in most of the common autophagy-mediated aging diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer’s, disease, as well as Paget’s disease of bone with or without frontotemporal dementia and inclusion body myopathy. Oxidative stress has serious damaging effects on the cellular contents: DNA, RNA, cellular proteins, and cellular organelles. Autophagy has a pivotal role in recycling these damaged non-functional organelles and misfolded or unfolded proteins. In this paper, we highlight, through a narrative review of the literature, that when autophagy processes are impaired during aging, in presence of cumulative air pollution-induced cellular oxidative stress and due to a direct effect on air pollutant, autophagy-mediated aging diseases may occur. PMID:25690002

Positive or negative involvement of heat shock proteins in multiple sclerosis pathogenesis: an overview.

PubMed

Turturici, Giuseppina; Tinnirello, Rosaria; Sconzo, Gabriella; Asea, Alexzander; Savettieri, Giovanni; Ragonese, Paolo; Geraci, Fabiana

2014-12-01

Multiple sclerosis (MS) is the most diffuse chronic inflammatory disease of the central nervous system. Both immune-mediated and neurodegenerative processes apparently play roles in the pathogenesis of this disease. Heat shock proteins (HSPs) are a family of highly evolutionarily conserved proteins; their expression in the nervous system is induced in a variety of pathologic states, including cerebral ischemia, neurodegenerative diseases, epilepsy, and trauma. To date, investigators have observed protective effects of HSPs in a variety of brain disease models (e.g. of Alzheimer disease and Parkinson disease). In contrast, unequivocal data have been obtained for their roles in MS that depend on the HSP family and particularly on their localization (i.e. intracellular or extracellular). This article reviews our current understanding of the involvement of the principal HSP families in MS.

Pulmonary disease at autopsy in patients with the acquired immunodeficiency syndrome.

PubMed

Wallace, J M; Hannah, J B

1988-08-01

To characterize the postmortem pulmonary disease and analyze the effectiveness of antemortem diagnosis, we examined the clinical records and autopsy material from 54 patients who died of the acquired immunodeficiency syndrome. At autopsy, all patients had pulmonary disease. One or more specific diagnoses were made in 53, including opportunistic infection, nonopportunistic infection, and Kaposi's sarcoma. Multiple postmortem pulmonary diagnoses were established in 37. Respiratory failure was the most common cause of death. Of the 97 pulmonary disorders discovered at autopsy, only 31 were diagnosed before death. The frequency with which infections were diagnosed during life varied according to the organism, and was significantly higher for Pneumocystis carinii than for cytomegalovirus or bacterial agents. Pulmonary Kaposi's sarcoma was diagnosed in only 7% of patients with autopsy documentation. The yield of diagnostic procedures also varied according to the disease present. Sputum culture was relatively effective in detecting Cryptococcus neoformans and Mycobacterium avium-intracellulare, fiber-optic bronchoscopy was extremely useful for diagnosing P Carinii, and one or more diagnoses were provided in 4 of 7 patients who underwent thoracotomy, but significant disease including cytomegalovirus infection and pulmonary Kaposi's sarcoma was frequently missed. Although the spectrum of lung disease found at autopsy is similar to that observed during life, the frequency of some pathologic processes including cytomegalovirus infection and Kaposi's sarcoma may be underrepresented in antemortem series.

Pulmonary Disease at Autopsy in Patients With the Acquired Immunodeficiency Syndrome

PubMed Central

Wallace, Jeanne M.; Hannah, James B.

1988-01-01

To characterize the postmortem pulmonary disease and analyze the effectiveness of antemortem diagnosis, we examined the clinical records and autopsy material from 54 patients who died of the acquired immunodeficiency syndrome. At autopsy, all patients had pulmonary disease. One or more specific diagnoses were made in 53, including opportunistic infection, nonopportunistic infection, and Kaposi's sarcoma. Multiple postmortem pulmonary diagnoses were established in 37. Respiratory failure was the most common cause of death. Of the 97 pulmonary disorders discovered at autopsy, only 31 were diagnosed before death. The frequency with which infections were diagnosed during life varied according to the organism, and was significantly higher for Pneumocystis carinii than for cytomegalovirus or bacterial agents. Pulmonary Kaposi's sarcoma was diagnosed in only 7% of patients with autopsy documentation. The yield of diagnostic procedures also varied according to the disease present. Sputum culture was relatively effective in detecting Cryptococcus neoformans and Mycobacterium avium-intracellulare, fiber-optic bronchoscopy was extremely useful for diagnosing P Carinii, and one or more diagnoses were provided in 4 of 7 patients who underwent thoracotomy, but significant disease including cytomegalovirus infection and pulmonary Kaposi's sarcoma was frequently missed. Although the spectrum of lung disease found at autopsy is similar to that observed during life, the frequency of some pathologic processes including cytomegalovirus infection and Kaposi's sarcoma may be underrepresented in antemortem series. PMID:3266812

[The clinical and microbiological characteristics of oropharyngeal candidiasis in the HIV-infected patients at the late stages of the disease].

PubMed

Charushin, A O; Elovikov, A M; Charushina, I P; Vorob'eva, N N; Katretskaya, G G

Oropharyngeal candidiasis in 512 HIV-infected patients at the late stages of the disease was studied with special reference to the clinical and microbiological characteristics of this condition. The diagnosis was established based on the results of the clinical and microbiological examination of the patients including investigation of the tissue samples taken from the oral cavity and the throat with the use of the device specially developed for this purpose. It was shown that the disease existed in various clinical forms the most common of which were monocomponent pathology represented by pseudomembranous candidiasis in 37.5±2.14% of the patients, the two-component mixed form (pseudomembranous candidiasis with concomitant angular chelitis) diagnosed in 27.5±1.97% cases, and the ternary form (the combination of pseudomembranous candidiasis, acute atrophic process, and angular chelitis) documented in 11.9±1.43% patients. The main clinical features of the disease included the combination of its various forms, multiple localization of the pathological process, and its polymorphous manifestations. Changes in the clinical course of oropharyngeal candidiasis associated with the progression of HIV from the 4A to the 4B stage were detected for the first time. They were shown to be accompanied by variations in the species composition and concentration of fungal flora in the crypts of the palatine tonsils and its sensitivity to fluconazole therapy.

Cardiac consequences of diabetes mellitus.

PubMed

Shehadeh, A; Regan, T J

1995-06-01

A variety of disciplines including noninvasive and invasive cardiac methodologies, as well as epidemiologic studies, have provided information that has altered our view on the relation of diabetes to cardiac disease. Instead of an exclusive focus on coronary artery disease, it is now recognized that heart muscle can be independently involved in diabetic patients. In diabetics without known cardiac disease, abnormalities of left ventricular mechanical function have been demonstrated in 40 to 50% of subjects, and it is primarily a diastolic phenomenon. Left ventricular hypertrophy may eventually appear in the absence of hypertension. The diastolic dysfunction appears related to interstitial collagen deposition, largely attributable to diminished degradation. The presence of even moderate obesity intensifies the abnormality. Reversibility of this process is not readily achieved with chronic insulin therapy. Experimental studies have indicated normalization of the collagen alteration by endurance training, begun relatively early in the disease process. General measures of management include the control of other cardiac risk factors and a reasonable program of physical activity. The high mortality during an initial acute myocardial infarction has been attributed to heart failure, which is managed as in nondiabetic patients. Recently, the early introduction of aspirin, thrombolysis, and beta-adrenergic blockade has reduced mortality during the initial infarction. Chronic use of the latter agent over the subsequent years has also proven to be more beneficial in diabetic patients with acute myocardial infarction compared with nondiabetic patients.

Complications of gastro-oesophageal reflux disease.

PubMed

Parasa, S; Sharma, P

2013-06-01

Gastro-oesophageal reflux disease (GORD) is on the rise with more than 20% of the western population reporting symptoms and is the most common gastrointestinal disorder in the United States. This increase in GORD is not exactly clear but has been attributed to the increasing prevalence of obesity, changing diet, and perhaps the decreasing prevalence of H. pylori infection. Complications of GORD could be either benign or malignant. Benign complications include erosive oesophagitis, bleeding and peptic strictures. Premalignant and malignant lesions include Barrett's metaplasia, and oesophageal cancer. Management of both the benign and malignant complications can be challenging. With the use of proton-pump inhibitors, peptic strictures (i.e., strictures related to reflux) have significantly declined. Several aspects of Barrett's management remain controversial including the stage in the disease process which needs to be intervened, type of the intervention and surveillance of these lesions to prevent development of high grade dysplasia and oesophageal adenocarcinoma. Copyright © 2013 Elsevier Ltd. All rights reserved.

Salivary metabolomics in the diagnosis of oral cancer and periodontal diseases.

PubMed

Mikkonen, J J W; Singh, S P; Herrala, M; Lappalainen, R; Myllymaa, S; Kullaa, A M

2016-08-01

Metabolomics is a systemic study of metabolites, which are small molecules generated by the process of metabolism. The metabolic profile of saliva can provide an early outlook of the changes associated with a wide range of diseases, including oral cancer and periodontal diseases. It is possible to measure levels of disease-specific metabolites using different methods as presented in this study. However, many challenges exist including incomplete understanding of the complicated metabolic pathways of different oral diseases. The review concludes with the discussion on future perspectives of salivary metabolomics from a clinician point of view. Salivary metabolomics may afford a new research avenue to identify local and systemic disorders but also to aid in the design and modification of therapies. A MEDLINE search using keywords "salivary metabolomics" returned 23 results in total, of which seven were omitted for being reviews or letters to the editor. The rest of the articles were used for preparation of the review, 13 of these were published in the last 5 years. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Facebook Groups for the Management of Chronic Diseases.

PubMed

Partridge, Stephanie R; Gallagher, Patrick; Freeman, Becky; Gallagher, Robyn

2018-01-17

The use of Facebook groups by health care researchers and professionals for chronic disease management, namely type 2 diabetes mellitus and coronary heart disease, is in its early stages and challenges are emerging. While Facebook groups offer great potential to deliver health support, research of Facebook groups for chronic disease management remains in its infancy, with robust evidence not yet available. Designing Facebook groups that are acceptable to users, health care researchers as well as health care professionals is a challenge, and there is a poor fit with traditional research and evaluation methods. Key recommendations for future research of Facebook groups for chronic disease management include: (1) iterative content development with input from the target patient population; (2) further understanding of the potential role of group "champions"; (3) ensuring the social media policies of health care institutions allow for real time online communication; and (4) utilizing comprehensive evaluation strategies, including the use of process evaluations. ©Stephanie R Partridge, Patrick Gallagher, Becky Freeman, Robyn Gallagher. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 17.01.2018.

Distributed and grid computing projects with research focus in human health.

PubMed

Diomidous, Marianna; Zikos, Dimitrios

2012-01-01

Distributed systems and grid computing systems are used to connect several computers to obtain a higher level of performance, in order to solve a problem. During the last decade, projects use the World Wide Web to aggregate individuals' CPU power for research purposes. This paper presents the existing active large scale distributed and grid computing projects with research focus in human health. There have been found and presented 11 active projects with more than 2000 Processing Units (PUs) each. The research focus for most of them is molecular biology and, specifically on understanding or predicting protein structure through simulation, comparing proteins, genomic analysis for disease provoking genes and drug design. Though not in all cases explicitly stated, common target diseases include research to find cure against HIV, dengue, Duchene dystrophy, Parkinson's disease, various types of cancer and influenza. Other diseases include malaria, anthrax, Alzheimer's disease. The need for national initiatives and European Collaboration for larger scale projects is stressed, to raise the awareness of citizens to participate in order to create a culture of internet volunteering altruism.

Experimental Evidence of ω-3 Polyunsaturated Fatty Acid Modulation of Inflammatory Cytokines and Bioactive Lipid Mediators: Their Potential Role in Inflammatory, Neurodegenerative, and Neoplastic Diseases

PubMed Central

Calviello, Gabriella; Su, Hui-Min; Weylandt, Karsten H.; Fasano, Elena; Serini, Simona; Cittadini, Achille

2013-01-01

A large body of evidence has emerged over the past years to show the critical role played by inflammation in the pathogenesis of several diseases including some cardiovascular, neoplastic, and neurodegenerative diseases, previously not considered inflammation-related. The anti-inflammatory action of ω-3 polyunsaturated fatty acids (PUFAs), as well as their potential healthy effects against the development and progression of the same diseases, has been widely studied by our and others' laboratories. As a result, a rethinking is taking place on the possible mechanisms underlying the beneficial effects of ω-3 PUFAs against these disorders, and, in particular, on the influence that they may exert on the molecular pathways involved in inflammatory process, including the production of inflammatory cytokines and lipid mediators active in the resolving phase of inflammation. In the present review we will summarize and discuss the current knowledge regarding the modulating effects of ω-3 PUFAs on the production of inflammatory cytokines and proresolving or protective lipid mediators in the context of inflammatory, metabolic, neurodegenerative, and neoplastic diseases. PMID:23691510

[Effect of smoking on neutrophil oxidative metabolism].

PubMed

Zasimauskas, Darius; Zekonis, Gediminas

2008-01-01

Alterations in neutrophil function by tobacco products may play a central role in the pathogenesis of periodontal diseases and several smoking-related systemic diseases. The aim of the study was to evaluate the effect of smoking on neutrophil oxidative metabolism. The study included 17 smoking men free of systemic diseases who were referred for treatment of various odontological diseases to outpatient department of Kaunas University of Medicine Hospital. The age of subjects varied from 22 to 43 years. All subjects answered the questions about smoking habits. Clinical examination included assessment of oral hygiene status according to the OHI-s index and periodontal status according to Russell and Ramfjord indices. To evaluate the oxidative metabolism of neutrophils, luminol- and liucigenin-dependent chemiluminescence and nitroblue tetrazolium test were used. After smoking, extracellular liucigenin-dependent chemiluminescence response was higher as compared to the response before smoking, but total (intra- and extracellular) luminol-dependent chemiluminescence response was the same both before and after smoking. Exposure of neutrophils to smoking caused a significant increase in nitroblue tetrazolium reduction. The release of reactive oxygen species in neutrophils exposed to smoking may alter the pathogenic processes in periodontal diseases.

Staphylococcus aureus and Staphylococcal Food-Borne Disease: An Ongoing Challenge in Public Health

PubMed Central

Smith, Tara C.

2014-01-01

Staphylococcal food-borne disease (SFD) is one of the most common food-borne diseases worldwide resulting from the contamination of food by preformed S. aureus enterotoxins. It is one of the most common causes of reported food-borne diseases in the United States. Although several Staphylococcal enterotoxins (SEs) have been identified, SEA, a highly heat-stable SE, is the most common cause of SFD worldwide. Outbreak investigations have found that improper food handling practices in the retail industry account for the majority of SFD outbreaks. However, several studies have documented prevalence of S. aureus in many food products including raw retail meat indicating that consumers are at potential risk of S. aureus colonization and subsequent infection. Presence of pathogens in food products imposes potential hazard for consumers and causes grave economic loss and loss in human productivity via food-borne disease. Symptoms of SFD include nausea, vomiting, and abdominal cramps with or without diarrhea. Preventive measures include safe food handling and processing practice, maintaining cold chain, adequate cleaning and disinfection of equipment, prevention of cross-contamination in home and kitchen, and prevention of contamination from farm to fork. This paper provides a brief overview of SFD, contributing factors, risk that it imposes to the consumers, current research gaps, and preventive measures. PMID:24804250

Higher coronary heart disease and heart attack morbidity in Appalachian coal mining regions.

PubMed

Hendryx, Michael; Zullig, Keith J

2009-11-01

This study analyzes the U.S. 2006 Behavioral Risk Factor Surveillance System survey data (N=235,783) to test whether self-reported cardiovascular disease rates are higher in Appalachian coal mining counties compared to other counties after control for other risks. Dependent variables include self-reported measures of ever (1) being diagnosed with cardiovascular disease (CVD) or with a specific form of CVD including (2) stroke, (3) heart attack, or (4) angina or coronary heart disease (CHD). Independent variables included coal mining, smoking, BMI, drinking, physician supply, diabetes co-morbidity, age, race/ethnicity, education, income, and others. SUDAAN Multilog models were estimated, and odds ratios tested for coal mining effects. After control for covariates, people in Appalachian coal mining areas reported significantly higher risk of CVD (OR=1.22, 95% CI=1.14-1.30), angina or CHD (OR=1.29, 95% CI=1.19-1.39) and heart attack (OR=1.19, 95% CI=1.10-1.30). Effects were present for both men and women. Cardiovascular diseases have been linked to both air and water contamination in ways consistent with toxicants found in coal and coal processing. Future research is indicated to assess air and water quality in coal mining communities in Appalachia, with corresponding environmental programs and standards established as indicated.

Nasal neuron PET imaging quantifies neuron generation and degeneration

PubMed Central

Van de Bittner, Genevieve C.; Riley, Misha M.; Cao, Luxiang; Herrick, Scott P.; Ricq, Emily L.; O’Neill, Michael J.; Ahmed, Zeshan; Murray, Tracey K.; Smith, Jaclyn E.; Wang, Changning; Schroeder, Frederick A.; Albers, Mark W.; Hooker, Jacob M.

2017-01-01

Olfactory dysfunction is broadly associated with neurodevelopmental and neurodegenerative diseases and predicts increased mortality rates in healthy individuals. Conventional measurements of olfactory health assess odor processing pathways within the brain and provide a limited understanding of primary odor detection. Quantification of the olfactory sensory neurons (OSNs), which detect odors within the nasal cavity, would provide insight into the etiology of olfactory dysfunction associated with disease and mortality. Notably, OSNs are continually replenished by adult neurogenesis in mammals, including humans, so OSN measurements are primed to provide specialized insights into neurological disease. Here, we have evaluated a PET radiotracer, [11C]GV1-57, that specifically binds mature OSNs and quantifies the mature OSN population in vivo. [11C]GV1-57 monitored native OSN population dynamics in rodents, detecting OSN generation during postnatal development and aging-associated neurodegeneration. [11C]GV1-57 additionally measured rates of neuron regeneration after acute injury and early-stage OSN deficits in a rodent tauopathy model of neurodegenerative disease. Preliminary assessment in nonhuman primates suggested maintained uptake and saturable binding of [18F]GV1-57 in primate nasal epithelium, supporting its translational potential. Future applications for GV1-57 include monitoring additional diseases or conditions associated with olfactory dysregulation, including cognitive decline, as well as monitoring effects of neuroregenerative or neuroprotective therapeutics. PMID:28112682

Development of pediatric vaccine recommendations and policies.

PubMed

Pickering, Larry K; Orenstein, Walter A

2002-07-01

A significant decrease in each vaccine-preventable disease has occurred since the introduction of the respective immunizations now included in the recommended childhood immunization schedule. The process through which a vaccine must travel from development to approval and implementation is complex. Hurdles include receiving approval from several advisory committees, government agencies, and professional organizations. At each step in the process, data regarding safety, immunogenicity, and efficacy are evaluated continuously and rigorously. Once a vaccine is approved by the Food and Drug Administration (FDA) and incorporated into the recommended childhood immunization schedule, continuing issues include those that deal with supply, safety, effectiveness, and financing. The logistics of development and implementation of pediatric vaccine recommendations and policies are reviewed.

Mammalian Krüppel-Like Factors in Health and Diseases

PubMed Central

McConnell, Beth B.; Yang, Vincent W.

2010-01-01

The Krüppel-like factor (KLF) family of transcription factors regulates diverse biological processes that include proliferation, differentiation, growth, development, survival, and responses to external stress. Seventeen mammalian KLFs have been identified, and numerous studies have been published that describe their basic biology and contribution to human diseases. KLF proteins have received much attention because of their involvement in the development and homeostasis of numerous organ systems. KLFs are critical regulators of physiological systems that include the cardiovascular, digestive, respiratory, hematological, and immune systems and are involved in disorders such as obesity, cardiovascular disease, cancer, and inflammatory conditions. Furthermore, KLFs play an important role in reprogramming somatic cells into induced pluripotent stem (iPS) cells and maintaining the pluripotent state of embryonic stem cells. As research on KLF proteins progresses, additional KLF functions and associations with disease are likely to be discovered. Here, we review the current knowledge of KLF proteins and describe common attributes of their biochemical and physiological functions and their pathophysiological roles. PMID:20959618

Lifestyle Choices Fuel Epidemics of Diabetes and Cardiovascular Disease Among Asian Indians.

PubMed

O'Keefe, Evan L; DiNicolantonio, James J; Patil, Harshal; Helzberg, John H; Lavie, Carl J

2016-01-01

Within the next 15years, India is projected to overtake China as the world's most populous nation. Due to the rapid pace of urbanization and modernization fueling population growth, in conjunction with a genetic predisposition to insulin resistance, India is suffering a rising epidemic of non-communicable diseases (NCDs), including coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), and stroke. In addition to the genetic predisposition, major negative lifestyle factors are contributing to the alarming outbreak of cardiovascular disease (CVD) among the Asian Indian population; these factors include: 1) a diet high in added sugar, refined grains and other processed foods, 2) physical inactivity, 3) vitamin D deficiency (VDD), and 4) smoking/pollution. These risk factors are all highly modifiable, and steps to improve these issues should be taken urgently to avoid a worsening NCD crisis among the inhabitants of the South Asian subcontinent as well as for people with Asian Indian ethnicity worldwide. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapy of spondylarthropathy in inflammatory bowel disease.

PubMed

Generini, S; Fiori, G; Matucci Cerinic, M

2002-01-01

Musculoskeletal manifestations represent the most common extra-intestinal complication of inflammatory bowel diseases (IBD) and are usually included in the clinical spectrum of the spondyloarthropathies (SpA). Although control of intestinal inflammation often ameliorates articular symptoms, sometimes arthropathy is independent of the gut disease course and may require the same therapeutic options which apply to primary SpA diseases, but with caution so as not aggravate the IBD. At the moment, salicylates (sulphasalazine and mesalazine) and selective COX-2 inhibitors (which are preferable to traditional NSAIDs although they cannot be assumed to be safe for the gastrointestinal tract) are the first choice treatment. Several immunosuppressive and biological agents including methotrexate, thalidomide and TNFalpha antagonists have efficacy for both articular and intestinal inflammation and are currently in use for the induction of remission and for maintenance in more severe cases. New combination therapies and novel biologically-driven treatments, targeted to specific pathophysiological processes, might offer less toxicity and the potential for better treatment outcomes.

[Fund for Protection against Catastrophic Expenses].

PubMed

Aracena-Genao, Belkis; González-Robledo, María Cecilia; González-Robledo, Luz María; Palacio-Mejía, Lina Sofía; Nigenda-López, Gustavo

2011-01-01

To document the status of operational and managerial processes of the Fund for Protection against Catastrophic Expenses (FPGC), as well as to describe its evolution, and to explore the relationship between covered diseases and the Mexican health profile. This is a joint management study, which included a qualitative and a quantitative phase. We conducted semi-structured interviews with key informants. We also analyzed the records of CNPSS, the hospital discharge and mortality data bases. Fifty two percent of the states take twice as long to report and validate the cases. From 2004-2009 the FPGC increased its coverage from 6 to 49 interventions, that means a spending increase of 2 306.4% in nominal terms and 1 659.3% in real terms. The HIV/AIDS was the intervention prioritized with 39.3% and Mexico City had the highest proportion of expenditure (25.1%). A few diseases included in the health profile are covered by the FPGC. The review of the inclusion criteria of diseases is urgent, so as to cover diseases of epidemiological importance.

[Inpatients days in patients with respiratory diseases and periodontal disease].

PubMed

Fernández-Plata, Rosario; Olmedo-Torres, Daniel; Martínez-Briseño, David; González-Cruz, Herminia; Casa-Medina, Guillermo; García-Sancho, Cecilia

2017-01-01

Periodontal disease is a chronic inflammatory gingival process that has been associated with the severity of respiratory diseases. In Mexico a prevalence of 78% was found in population with social security and > 60 years old. The aim of this study is to establish the association between periodontal disease and respiratory diseases according to the inpatient days. A cross-sectional study was conducted from January to December 2011. We included hospitalized patients, ≥ 18 years of age, without sedation or intubated. A dentist classified patients into two groups according to the severity of the periodontal disease: mild-to-moderate and severe. We estimated medians of inpatient days by disease and severity. Negative binomial models were adjusted to estimate incidence rate ratios and predicted inpatient days. 3,059 patients were enrolled. The median of observed and predicted inpatient days was higher in the group of severe periodontal disease (p < 0.05). Patients with chronic obstructive pulmonary disease, tuberculosis, and influenza had the highest incidence rates ratios of periodontal disease (p < 0.05). The severity of periodontal disease is positively -associated with inpatient days of patients with respiratory diseases.

Recommendations from the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL).

PubMed

Annemans, Lieven; Aymé, Ségolène; Le Cam, Yann; Facey, Karen; Gunther, Penilla; Nicod, Elena; Reni, Michele; Roux, Jean-Louis; Schlander, Michael; Taylor, David; Tomino, Carlo; Torrent-Farnell, Josep; Upadhyaya, Sheela; Hutchings, Adam; Le Dez, Lugdivine

2017-03-10

Rare diseases are an important public health issue with high unmet need. The introduction of the EU Regulation on orphan medicinal products (OMP) has been successful in stimulating investment in the research and development of OMPs. Despite this advancement, patients do not have universal access to these new medicines. There are many factors that affect OMP uptake, but one of the most important is the difficulty of making pricing and reimbursement (P&R) decisions in rare diseases. Until now, there has been little consensus on the most appropriate assessment criteria, perspective or appraisal process. This paper proposes nine principles to help improve the consistency of OMP P&R assessment in Europe and ensure that value assessment, pricing and funding processes reflect the specificities of rare diseases and contribute to both the sustainability of healthcare systems and the sustainability of innovation in this field. These recommendations are the output of the European Working Group for Value Assessment and Funding Processes in Rare Diseases (ORPH-VAL), a collaboration between rare disease experts, patient representatives, academics, health technology assessment (HTA) practitioners, politicians and industry representatives. ORPH-VAL reached its recommendations through careful consideration of existing OMP P&R literature and through a wide consultation with expert stakeholders, including payers, regulators and patients. The principles cover four areas: OMP decision criteria, OMP decision process, OMP sustainable funding systems and European co-ordination. This paper also presents a guide to the core elements of value relevant to OMPs that should be consistently considered in all OMP appraisals. The principles outlined in this paper may be helpful in drawing together an emerging consensus on this topic and identifying areas where consistency in payer approach could be achievable and beneficial. All stakeholders have an obligation to work together to ensure that the promise of OMP's is realised.

Development and Operation of Space-Based Disease Early Warning Models

NASA Astrophysics Data System (ADS)

John, M. M.

2010-12-01

Millions of people die every year from preventable diseases such as malaria and cholera. Pandemics put the entire world population at risk and have the potential to kill thousands and cripple the global economy. In light of these dangers, it is fortunate that the data and imagery gathered by remote sensing satellites can be used to develop models that predict areas at risk for outbreaks. These warnings can help decision makers to distribute preventative medicine and other forms of aid to save lives. There are already many Earth observing satellites in orbit with the ability to provide data and imagery. Researchers have created a number of models based on this information, and some are being used in real-life situations. These capabilities should be further developed and supported by governments and international organizations to benefit as many people as possible. To understand the benefits and challenges of disease early warning models, it is useful to understand how they are developed. A number of steps must occur for satellite data and imagery to be used to prevent disease outbreaks; each requires a variety of inputs and may include a range of experts and stakeholders. This paper discusses the inputs, outputs, and basic processes involved in each of six main steps to developing models, including: identifying and validating links between a disease and environmental factors, creating and validating a software model to predict outbreaks, transitioning a model to operational use, using a model operationally, and taking action on the data provided by the model. The paper briefly overviews past research regarding the link between remote sensing data and disease, and identifies ongoing research in academic centers around the world. The activities of three currently operational models are discussed, including the U.S. Department of Defense Global Emerging Infections Surveillance and Response System (DoD-GEIS), NASA carries out its Malaria Modeling and Surveillance program, and the The Mapping Malaria Risk in Africa (MARA) program. Based on the understanding of basic processes as well as the experience of currently operational programs, the paper offers a number of recommendations to governments and researchers for future development of operational disease early warning programs.

Diffuse Parenchymal Diseases Associated With Aluminum Use and Primary Aluminum Production

PubMed Central

2014-01-01

Aluminum use and primary aluminum production results in the generation of various particles, fumes, gases, and airborne materials with the potential for inducing a wide range of lung pathology. Nevertheless, the presence of diffuse parenchymal or interstitial lung disease related to these processes remains controversial. The relatively uncommon occurrence of interstitial lung diseases in aluminum-exposed workers—despite the extensive industrial use of aluminum—the potential for concurrent exposure to other fibrogenic fibers, and the previous use of inhaled aluminum powder for the prevention of silicosis without apparent adverse respiratory effects are some of the reasons for this continuing controversy. Specific aluminum-induced parenchymal diseases described in the literature, including existing evidence of interstitial lung diseases, associated with primary aluminum production are reviewed. PMID:24806728

Legg-Calvé-Perthes disease.

PubMed

Schoenecker, P L

1986-09-01

Legg-Calvé-Perthes disease, or osteochondrosis of the femoral head, occurs predominantly in boys 4 to 7 years of age. The disease progresses through synovitis, necrosis, fragmentation, and a residual stage. Outcome can be affected by age at disease onset, the extent of femoral head involvement as determined by x-ray, and the degree to which normal range of motion is maintained. The goal of treatment is to minimize residual deformity of the femoral head and acetabulum. This is accomplished by containing the femoral head well within the acetabulum and maintaining range of motion while the disease process runs its course. In extremely young patients, containment is often achieved during normal daily living activities. Containment treatment methods include abduction casting or orthosis; surgical containment can be accomplished by femoral or innominate osteotomy.

[Reevaluation for systematic reviews for traditional Chinese medicine injections for coronary disease].

PubMed

Yin, Xiu-Ping; Xie, Yan-Ming; Liao, Xing; Luo, Man

2016-11-01

To reevaluate the systematic reviews for traditional Chinese medicine(TCM) injections for treating coronary disease, data in four Chinese databases and PubMed, Embase, Cochrane Library, Wed of Science OVID from inception until May 2016 were searched. We extracted data according to the AMSTAR and PRISMA checklists to evaluate the methodological quality and reporting characteristics of included literatures. A total of 69 systematic reviews were included, involving 24 TCM injections, which showed certain efficacy in treating coronary disease, and whose main outcome indexes included alleviation of symptoms of angina pectoris and electrocardiogram. In all of the systematic reviews, the duration of follow-up were not reported. Six systematic reviews reported TCM typing. In the 44 system reviews, 1 335 reports mentioned 4 137 adverse events. According to the results of AMSTAR and PRISMA checklists, the quality assessment scores about included studies were not high, and most of the systematic reviews suffered heterogeneity and irrational processing of forest plots. In conclusion, TCM injections in the treatment of coronary disease have a wide range and positive effects. However, affected by the low quality of systematic reviews and the production of reevaluation, the study had some limitations. Therefore, the systematic reviews shall be further improved, in order to provide more advanced clinical evidences to clinicians. Copyright© by the Chinese Pharmaceutical Association.

Diabetes and Alzheimer's Disease: Can Tea Phytochemicals Play a Role in Prevention?

PubMed

Fernando, Warnakulasuriya M A D B; Somaratne, Geeshani; Goozee, Kathryn G; Williams, Shehan; Singh, Harjinder; Martins, Ralph N

2017-01-01

Dementia and diabetes mellitus are prevalent disorders in the elderly population. While recognized as two distinct diseases, diabetes has more recently recognized as a significant contributor to risk for developing dementia, and some studies make reference to type 3 diabetes, a condition resulting from insulin resistance in the brain. Alzheimer's disease, the most common form of dementia, and diabetes, interestingly, share underlying pathological processes, commonality in risk factors, and, importantly, pathways for intervention. Tea has been suggested to possess potent antioxidant properties. It is rich in phytochemicals including, flavonoids, tannins, caffeine, polyphenols, boheic acid, theophylline, theobromine, anthocyanins, gallic acid, and finally epigallocatechin-3-gallate, which is considered to be the most potent active ingredient. Flavonoid phytochemicals, known as catechins, within tea offer potential benefits for reducing the risk of diabetes and Alzheimer's disease by targeting common risk factors, including obesity, hyperlipidemia, hypertension, cardiovascular disease, and stroke. Studies also show that catechins may prevent the formation of amyloid-β plaques and enhance cognitive functions, and thus may be useful in treating patients who have Alzheimer's disease or dementia. Furthermore, other phytochemicals found within tea offer important antioxidant properties along with innate properties capable of modulating intracellular neuronal signal transduction pathways and mitochondrial function.

Fish mucus alters the Flavobacterium columnare transcriptome

USDA-ARS?s Scientific Manuscript database

Columnaris disease which is caused by Flavobacterium columnare severely impacts the production of freshwater finfish species. Due to the impact on the aquaculture industry, research efforts to better understand the biological processes of F. columnare including the formation of biofilms and their co...

Consumption of minimally processed food is inversely associated with excess weight in adolescents living in an underdeveloped city.

PubMed

Melo, Ingrid Sofia Vieira de; Costa, Clara Andrezza Crisóstomo Bezerra; Santos, João Victor Laurindo Dos; Santos, Aldenir Feitosa Dos; Florêncio, Telma Maria de Menezes Toledo; Bueno, Nassib Bezerra

2017-01-01

The consumption of ultra-processed foods may be associated with the development of chronic diseases, both in adults and in children/adolescents. This consumption is growing worldwide, especially in low and middle-income countries. Nevertheless, its magnitude in small, poor cities from the countryside is not well characterized, especially in adolescents. This study aimed to assess the consumption of minimally processed, processed and ultra-processed foods by adolescents from a poor Brazilian city and to determine if it was associated with excess weight, high waist circumference and high blood pressure. Cross-sectional study, conducted at a public federal school that offers technical education together with high school, located in the city of Murici. Adolescents of both sexes and aged between 14-19 years old were included. Anthropometric characteristics (weight, height, waist circumference), blood pressure, and dietary intake data were assessed. Associations were calculated using Poisson regression models, adjusted by sex and age. At total, 249 adolescents were included, being 55.8% girls, with a mean age of 16 years-old. The consumption of minimally processed foods was inversely associated with excess weight (Adjusted Prevalence Ratio: 0.61, 95% Confidence Interval: [0.39-0.96], P = 0.03). Although the consumption of ultra-processed foods was not associated with excess weight, high blood pressure and high waist circumference, 46.2% of the sample reported eating these products more than weekly. Consumption of minimally processed food is inversely associated with excess weight in adolescents. Investments in nutritional education aiming the prevention of chronic diseases associated with the consumption of these foods are necessary.

Leveraging health information exchange to improve population health reporting processes: lessons in using a collaborative-participatory design process.

PubMed

Revere, Debra; Dixon, Brian E; Hills, Rebecca; Williams, Jennifer L; Grannis, Shaun J

2014-01-01

Surveillance, or the systematic monitoring of disease within a population, is a cornerstone function of public health. Despite significant investment in information technologies (IT) to improve the public's health, health care providers continue to rely on manual, spontaneous reporting processes that can result in incomplete and delayed surveillance activities. Participatory design principles advocate including real users and stakeholders when designing an information system to ensure high ecological validity of the product, incorporate relevance and context into the design, reduce misconceptions designers can make due to insufficient domain expertise, and ultimately reduce barriers to adoption of the system. This paper focuses on the collaborative and informal participatory design process used to develop enhanced, IT-enabled reporting processes that leverage available electronic health records in a health information exchange to prepopulate notifiable-conditions report forms used by public health authorities. Over nine months, public health stakeholders, technical staff, and informatics researchers were engaged in a multiphase participatory design process that included public health stakeholder focus groups, investigator-engineering team meetings, public health survey and census regarding high-priority data elements, and codesign of exploratory prototypes and final form mock-ups. A number of state-mandated report fields that are not highly used or desirable for disease investigation were eliminated, which allowed engineers to repurpose form space for desired and high-priority data elements and improve the usability of the forms. Our participatory design process ensured that IT development was driven by end user expertise and needs, resulting in significant improvements to the layout and functionality of the reporting forms. In addition to informing report form development, engaging with public health end users and stakeholders through the participatory design process provided new insights into public health workflow and allowed the team to quickly triage user requests while managing user expectations within the realm of engineering possibilities. Engaging public health, engineering staff, and investigators in a shared codesigning process ensured that the new forms will not only meet real-life needs but will also support development of a product that will be adopted and, ultimately, improve communicable and infectious disease reporting by clinicians to public health.

Differential roles of NADPH oxidases in vascular physiology and pathophysiology

PubMed Central

Amanso, Angelica M.; Griendling, Kathy K.

2012-01-01

Reactive oxygen species (ROS) are produced by all vascular cells and regulate the major physiological functions of the vasculature. Production and removal of ROS are tightly controlled and occur in discrete subcellular locations, allowing for specific, compartmentalized signaling. Among the many sources of ROS in the vessel wall, NADPH oxidases are implicated in physiological functions such as control of vasomotor tone, regulation of extracellular matrix and phenotypic modulation of vascular smooth muscle cells. They are involved in the response to injury, whether as an oxygen sensor during hypoxia, as a regulator of protein processing, as an angiogenic stimulus, or as a mechanism of wound healing. These enzymes have also been linked to processes leading to disease development, including migration, proliferation, hypertrophy, apoptosis and autophagy. As a result, NADPH oxidases participate in atherogenesis, systemic and pulmonary hypertension and diabetic vascular disease. The role of ROS in each of these processes and diseases is complex, and a more full understanding of the sources, targets, cell-specific responses and counterbalancing mechanisms is critical for the rational development of future therapeutics. PMID:22202108

Protein Tyrosine Phosphatase 1B (PTP1B): A Potential Target for Alzheimer's Therapy?

PubMed

Vieira, Marcelo N N; Lyra E Silva, Natalia M; Ferreira, Sergio T; De Felice, Fernanda G

2017-01-01

Despite significant advances in current understanding of mechanisms of pathogenesis in Alzheimer's disease (AD), attempts at drug development based on those discoveries have failed to translate into effective, disease-modifying therapies. AD is a complex and multifactorial disease comprising a range of aberrant cellular/molecular processes taking part in different cell types and brain regions. As a consequence, therapeutics for AD should be able to block or compensate multiple abnormal pathological events. Here, we examine recent evidence that inhibition of protein tyrosine phosphatase 1B (PTP1B) may represent a promising strategy to combat a variety of AD-related detrimental processes. Besides its well described role as a negative regulator of insulin and leptin signaling, PTB1B recently emerged as a modulator of various other processes in the central nervous system (CNS) that are also implicated in AD. These include signaling pathways germane to learning and memory, regulation of synapse dynamics, endoplasmic reticulum (ER) stress and microglia-mediated neuroinflammation. We propose that PTP1B inhibition may represent an attractive and yet unexplored therapeutic approach to correct aberrant signaling pathways linked to AD.

A national survey of organizational transfer practices in chronic disease prevention in Canada.

PubMed

Hanusaik, Nancy; O'Loughlin, Jennifer L; Paradis, Gilles; Kishchuk, Natalie

2011-08-01

Underuse of best practices in chronic disease prevention (CDP) represents missed opportunities to promote healthy living and prevent chronic disease. Better understanding of how CDP programs, practices and policies (PPPs) are transferred from 'resource' organizations that develop them to 'user' organizations that implement them is crucial. The objectives of this work were to develop psychometrically sound measures of transfer practices occurring within resource organizations; describe the use of these transfer practices and identify correlates of the transfer process. Cross-sectional data were collected in structured telephone interviews with the person most knowledgeable about PPP transfer in 77 Canadian organizations that develop PPPs. Independent correlates of transfer were identified using multiple linear regression. The transfer practices most commonly used included: identification of barriers to PPP adoption/implementation, tailoring transfer strategies and designing a transfer plan. Skill at planning/implementing transfer, external sources of funding specifically allocated for transfer, type of resource organization, attitude toward process of collaboration and user-centeredness were all positively associated with the transfer process. These factors represent possible targets for interventions to improve transfer of CDP PPPs.

MitProNet: A Knowledgebase and Analysis Platform of Proteome, Interactome and Diseases for Mammalian Mitochondria

PubMed Central

Mao, Song; Chai, Xiaoqiang; Hu, Yuling; Hou, Xugang; Tang, Yiheng; Bi, Cheng; Li, Xiao

2014-01-01

Mitochondrion plays a central role in diverse biological processes in most eukaryotes, and its dysfunctions are critically involved in a large number of diseases and the aging process. A systematic identification of mitochondrial proteomes and characterization of functional linkages among mitochondrial proteins are fundamental in understanding the mechanisms underlying biological functions and human diseases associated with mitochondria. Here we present a database MitProNet which provides a comprehensive knowledgebase for mitochondrial proteome, interactome and human diseases. First an inventory of mammalian mitochondrial proteins was compiled by widely collecting proteomic datasets, and the proteins were classified by machine learning to achieve a high-confidence list of mitochondrial proteins. The current version of MitProNet covers 1124 high-confidence proteins, and the remainders were further classified as middle- or low-confidence. An organelle-specific network of functional linkages among mitochondrial proteins was then generated by integrating genomic features encoded by a wide range of datasets including genomic context, gene expression profiles, protein-protein interactions, functional similarity and metabolic pathways. The functional-linkage network should be a valuable resource for the study of biological functions of mitochondrial proteins and human mitochondrial diseases. Furthermore, we utilized the network to predict candidate genes for mitochondrial diseases using prioritization algorithms. All proteins, functional linkages and disease candidate genes in MitProNet were annotated according to the information collected from their original sources including GO, GEO, OMIM, KEGG, MIPS, HPRD and so on. MitProNet features a user-friendly graphic visualization interface to present functional analysis of linkage networks. As an up-to-date database and analysis platform, MitProNet should be particularly helpful in comprehensive studies of complicated biological mechanisms underlying mitochondrial functions and human mitochondrial diseases. MitProNet is freely accessible at http://bio.scu.edu.cn:8085/MitProNet. PMID:25347823

Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease.

PubMed

Ogino, Shuji; Lochhead, Paul; Chan, Andrew T; Nishihara, Reiko; Cho, Eunyoung; Wolpin, Brian M; Meyerhardt, Jeffrey A; Meissner, Alexander; Schernhammer, Eva S; Fuchs, Charles S; Giovannucci, Edward

2013-04-01

Epigenetics acts as an interface between environmental/exogenous factors, cellular responses, and pathological processes. Aberrant epigenetic signatures are a hallmark of complex multifactorial diseases (including neoplasms and malignancies such as leukemias, lymphomas, sarcomas, and breast, lung, prostate, liver, and colorectal cancers). Epigenetic signatures (DNA methylation, mRNA and microRNA expression, etc) may serve as biomarkers for risk stratification, early detection, and disease classification, as well as targets for therapy and chemoprevention. In particular, DNA methylation assays are widely applied to formalin-fixed, paraffin-embedded archival tissue specimens as clinical pathology tests. To better understand the interplay between etiological factors, cellular molecular characteristics, and disease evolution, the field of 'molecular pathological epidemiology (MPE)' has emerged as an interdisciplinary integration of 'molecular pathology' and 'epidemiology'. In contrast to traditional epidemiological research including genome-wide association studies (GWAS), MPE is founded on the unique disease principle, that is, each disease process results from unique profiles of exposomes, epigenomes, transcriptomes, proteomes, metabolomes, microbiomes, and interactomes in relation to the macroenvironment and tissue microenvironment. MPE may represent a logical evolution of GWAS, termed 'GWAS-MPE approach'. Although epigenome-wide association study attracts increasing attention, currently, it has a fundamental problem in that each cell within one individual has a unique, time-varying epigenome. Having a similar conceptual framework to systems biology, the holistic MPE approach enables us to link potential etiological factors to specific molecular pathology, and gain novel pathogenic insights on causality. The widespread application of epigenome (eg, methylome) analyses will enhance our understanding of disease heterogeneity, epigenotypes (CpG island methylator phenotype, LINE-1 (long interspersed nucleotide element-1; also called long interspersed nuclear element-1; long interspersed element-1; L1) hypomethylation, etc), and host-disease interactions. In this article, we illustrate increasing contribution of modern pathology to broader public health sciences, which attests pivotal roles of pathologists in the new integrated MPE science towards our ultimate goal of personalized medicine and prevention.

[Medical certification in workers involved in logging and wood-processing].

PubMed

Romankow, Jacek

2007-01-01

Activities involved in forestry and woodworking industry are associated with workers being exposed to numerous environmental and technology-related factors that are detrimental to their health. Such hazards include working in changeable climatic conditions, in the vicinity of heavy equipment, exposure to noise, chainsaw vibrations, enforced body positioning, hard physical work, the effect of exhaust gases, potential effects of biological factors, including epizootic diseases. Wood processing involves performing mechanical activities employing tools and machines, as well as processes utilizing various chemical substances. Forestry and woodworking industry workers may deal both with timber and with wood products. In medical certification, the following issues are of significance: work in the vicinity of rotational elements, noise, effects of chemicals or biological factors, including carcinogenic substances. For this reason, the procedures involved in medical examinations of such workers are complex.

Using the brain's fight-or-flight response for predicting mental illness on the human space flight program

NASA Astrophysics Data System (ADS)

Losik, L.

A predictive medicine program allows disease and illness including mental illness to be predicted using tools created to identify the presence of accelerated aging (a.k.a. disease) in electrical and mechanical equipment. When illness and disease can be predicted, actions can be taken so that the illness and disease can be prevented and eliminated. A predictive medicine program uses the same tools and practices from a prognostic and health management program to process biological and engineering diagnostic data provided in analog telemetry during prelaunch readiness and space exploration missions. The biological and engineering diagnostic data necessary to predict illness and disease is collected from the pre-launch spaceflight readiness activities and during space flight for the ground crew to perform a prognostic analysis on the results from a diagnostic analysis. The diagnostic, biological data provided in telemetry is converted to prognostic (predictive) data using the predictive algorithms. Predictive algorithms demodulate telemetry behavior. They illustrate the presence of accelerated aging/disease in normal appearing systems that function normally. Mental illness can predicted using biological diagnostic measurements provided in CCSDS telemetry from a spacecraft such as the ISS or from a manned spacecraft in deep space. The measurements used to predict mental illness include biological and engineering data from an astronaut's circadian and ultranian rhythms. This data originates deep in the brain that is also damaged from the long-term exposure to cortisol and adrenaline anytime the body's fight or flight response is activated. This paper defines the brain's FOFR; the diagnostic, biological and engineering measurements needed to predict mental illness, identifies the predictive algorithms necessary to process the behavior in CCSDS analog telemetry to predict and thus prevent mental illness from occurring on human spaceflight missions.

Bone and vitamin D metabolism in HIV.

PubMed

Panayiotopoulos, Aristotle; Bhat, Nandini; Bhangoo, Amrit

2013-06-01

Human immunodeficiency virus (HIV) infection has progressed to a chronic disease and HIV positive individuals are living longer lives. This has lead to an increase in morbidity and mortality due to secondary issues, one being HIV bone disease. HIV infected pediatric and adult populations have a greater incidence in reduction of BMD as compared to the controls. Osteoporosis has been reported to be present in up to 15 % of HIV positive patients. We are starting to understand the mechanism behind the changes in HIV bone disease. Viral proteins interfere with osteoblastic activity either by direct interaction or by the inflammatory process that they induce. Anti-viral management, including highly active antiretroviral therapy (HAART), protease inhibitors, and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) also are involved in disrupting proper bone metabolism. Vitamin D levels have strong correlation with bone disease in HIV patients, and are dependent not only to chronic disease state, but interaction of pharmacologic management and inflammatory process as well. Work up of the secondary causes of osteopenia and osteoporosis should be undertaken in all patients. DEXA scan is recommended in all post-menopausal women with HIV, all HIV infected men 50 years of age or older and in those with a history of fragility fractures regardless of age or gender. Preventive measures include adequate nutrition, calcium and Vitamin D intake daily, muscle strengthening and balance exercises to increase BMD and reduce fractures. Bisphosphonates are considered to be the first line for the treatment of HIV associated bone disease. This review will describe how the balanced mechanism of bone metabolism is interrupted by the HIV infection itself, the complications that arise from HIV/AIDS, and its treatment options.

The Impact of Mobile Health Interventions on Chronic Disease Outcomes in Developing Countries: A Systematic Review

PubMed Central

Lee, Allison G.; Willner, Jonathan M.; Jahangir, Eiman; Ciapponi, Agustín; Rubinstein, Adolfo

2014-01-01

Abstract Introduction: Rates of chronic diseases will continue to rise in developing countries unless effective and cost-effective interventions are implemented. This review aims to discuss the impact of mobile health (m-health) on chronic disease outcomes in low- and middle-income countries (LMIC). Materials and Methods: Systematic literature searches were performed using CENTRAL, MEDLINE, EMBASE, and LILACS databases and gray literature. Scientific literature was searched to identify controlled studies evaluating cell phone voice and text message interventions to address chronic diseases in adults in low- or middle-income countries. Outcomes measured included morbidity, mortality, hospitalization rates, behavioral or lifestyle changes, process of care improvements, clinical outcomes, costs, patient–provider satisfaction, compliance, and health-related quality of life (HRQoL). Results: From the 1,709 abstracts retrieved, 163 articles were selected for full text review, including 9 randomized controlled trials with 4,604 participants. Most of the studies addressed more than one outcome. Of the articles selected, six studied clinical outcomes, six studied processes of care, three examined healthcare costs, and two examined HRQoL. M-health positively impacted on chronic disease outcomes, improving attendance rates, clinical outcomes, and HRQoL, and was cost-effective. Conclusions: M-health is emerging as a promising tool to address access, coverage, and equity gaps in developing countries and low-resource settings. The results for m-health interventions showed a positive impact on chronic diseases in LMIC. However, a limiting factor of this review was the relatively small number of studies and patients enrolled, highlighting the need for more rigorous research in this area in developing countries. PMID:24205809

Multiple mechanisms of transmission of the Caribbean coral disease white plague

NASA Astrophysics Data System (ADS)

Clemens, E.; Brandt, M. E.

2015-12-01

White plague is one of the most devastating coral diseases in the Caribbean, and yet important aspects of its epidemiology, including how the disease transmits, remain unknown. This study tested potential mechanisms and rates of transmission of white plague in a laboratory setting. Transmission mechanisms including the transport of water, contact with macroalgae, and predation via corallivorous worms and snails were tested on the host species Orbicella annularis. Two of the tested mechanisms were shown to transmit disease: water transport and the corallivorous snail Coralliophila abbreviata. Between these transmission mechanisms, transport of water between a diseased coral and a healthy coral resulted in disease incidence significantly more frequently in exposed healthy corals. Transmission via water transport also occurred more quickly and was associated with higher rates of tissue loss (up to 3.5 cm d-1) than with the corallivorous snail treatment. In addition, water that was in contact with diseased corals but was filtered with a 0.22-μm filter prior to being introduced to apparently healthy corals also resulted in the transmission of disease signs, but at a much lower rate than when water was not filtered. This study has provided important information on the transmission potential of Caribbean white plague disease and highlights the need for a greater understanding of how these processes operate in the natural environment.

Tai Chi Exercise to Improve Non-Motor Symptoms of Parkinson's Disease.

PubMed

Nocera, Joe R; Amano, Shinichi; Vallabhajosula, Srikant; Hass, Chris J

2013-08-20

A substantial number of individuals with Parkinson's disease exhibit debilitating non-motor symptoms that decrease quality of life. To date, few treatment options exist for the non-motor symptomatology related to Parkinson's disease. The goal of this pilot investigation was to determine the effects of Tai Chi exercise on the non-motor symptomology in Parkinson's disease. Twenty-one individuals with Parkinson's disease were enrolled in a Tai Chi intervention (n=15) or a noncontact control group (n=6). Participants assigned to Tai Chi participated in 60-minute Tai Chi sessions three times per week, for 16 weeks. Pre and post measures included indices of cognitive-executive function including visuomotor tracking and attention, selective attention, working memory, inhibition, processing speed and task switching. Additionally, all participants were evaluated on the Parkinson's disease Questionnaire-39 and Tinetti's Falls Efficacy Scale. Results indicated that the Tai Chi training group had significantly better scores following the intervention than the control group on the Parkinson's disease Questionnaire-39 total score as well as the emotional well-being sub score. Trends for improvement were noted for the Tai Chi group on Digits Backwards, Tinetti's Falls Efficacy Scale, and the activities of daily living and communication sub scores of the Parkinson's disease Questionnaire-39. This research provides initial data that supports future studies to definitively establish efficacy of Tai Chi to improve non-motor features of Parkinson's disease.

Measuring diagnoses: ICD code accuracy.

PubMed

O'Malley, Kimberly J; Cook, Karon F; Price, Matt D; Wildes, Kimberly Raiford; Hurdle, John F; Ashton, Carol M

2005-10-01

To examine potential sources of errors at each step of the described inpatient International Classification of Diseases (ICD) coding process. The use of disease codes from the ICD has expanded from classifying morbidity and mortality information for statistical purposes to diverse sets of applications in research, health care policy, and health care finance. By describing a brief history of ICD coding, detailing the process for assigning codes, identifying where errors can be introduced into the process, and reviewing methods for examining code accuracy, we help code users more systematically evaluate code accuracy for their particular applications. We summarize the inpatient ICD diagnostic coding process from patient admission to diagnostic code assignment. We examine potential sources of errors at each step and offer code users a tool for systematically evaluating code accuracy. Main error sources along the "patient trajectory" include amount and quality of information at admission, communication among patients and providers, the clinician's knowledge and experience with the illness, and the clinician's attention to detail. Main error sources along the "paper trail" include variance in the electronic and written records, coder training and experience, facility quality-control efforts, and unintentional and intentional coder errors, such as misspecification, unbundling, and upcoding. By clearly specifying the code assignment process and heightening their awareness of potential error sources, code users can better evaluate the applicability and limitations of codes for their particular situations. ICD codes can then be used in the most appropriate ways.

Progressive hemifacial atrophy (Parry-Romberg syndrome). Case report.

PubMed

Mazzeo, N; Fisher, J G; Mayer, M H; Mathieu, G P

1995-01-01

Progressive hemifacial atrophy (Parry-Romberg syndrome) is a slowly progressing facial atrophy of subcutaneous fat and the wasting of associated skin, cartilage, and bone. This disorder includes an active progressive phase (2 to 10 years) followed by a burning out of the atrophic process with subsequent stability. This article presents a review of the literature and a case report with unique dental involvement as a result of this disease process.

Formation and Degradation of Beta-casomorphins in Dairy Processing

PubMed Central

Nguyen, Duc Doan; Johnson, Stuart Keith; Busetti, Francesco; Solah, Vicky Ann

2015-01-01

Milk proteins including casein are sources of peptides with bioactivity. One of these peptides is beta-casomorphin (BCM) which belongs to a group of opioid peptides formed from β-casein variants. Beta-casomorphin 7 (BCM7) has been demonstrated to be enzymatically released from the A1 or B β-casein variant. Epidemiological evidence suggests the peptide BCM 7 is a risk factor for development of human diseases, including increased risk of type 1 diabetes and cardiovascular diseases but this has not been thoroughly substantiated by research studies. High performance liquid chromatography coupled to UV-Vis and mass spectrometry detection as well as enzyme–linked immunosorbent assay (ELISA) has been used to analyze BCMs in dairy products. BCMs have been detected in raw cow's milk and human milk and a variety of commercial cheeses, but their presence has yet to be confirmed in commercial yoghurts. The finding that BCMs are present in cheese suggests they could also form in yoghurt, but be degraded during yoghurt processing. Whether BCMs do form in yoghurt and the amount of BCM forming or degrading at different processing steps needs further investigation and possibly will depend on the heat treatment and fermentation process used, but it remains an intriguing unknown. PMID:25077377

Angiogenic therapy for cardiac repair based on protein delivery systems.

PubMed

Formiga, F R; Tamayo, E; Simón-Yarza, T; Pelacho, B; Prósper, F; Blanco-Prieto, M J

2012-05-01

Cardiovascular diseases remain the first cause of morbidity and mortality in the developed countries and are a major problem not only in the western nations but also in developing countries. Current standard approaches for treating patients with ischemic heart disease include angioplasty or bypass surgery. However, a large number of patients cannot be treated using these procedures. Novel curative approaches under investigation include gene, cell, and protein therapy. This review focuses on potential growth factors for cardiac repair. The role of these growth factors in the angiogenic process and the therapeutic implications are reviewed. Issues including aspects of growth factor delivery are presented in relation to protein stability, dosage, routes, and safety matters. Finally, different approaches for controlled growth factor delivery are discussed as novel protein delivery platforms for cardiac regeneration.

Contribution of dot-blot assay to the diagnosis and management of myositis: a three-year practice at a university hospital centre.

PubMed

Martel, Clothilde; Vignaud, Guillaume; Liozon, Eric; Magy, Laurent; Gallouedec, Gael; Ly, Kim; Bezanahary, Holly; Cypierre, Anne; Lapébie, François-Xavier; Palat, Sylvain; Gondran, Guillaume; Jauberteau, Marie-Odile; Fauchais, Anne-Laure

2016-01-01

Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases with wide clinical spectrum that may lead to delayed diagnosis. The aim of this study was to examine the impact of IIM-specific dot-blot assay on diagnostic process of patients presenting with muscular or systemic symptoms evocating of IIM. We collected all the prescriptions of an IIM specific dot-blot assay (8 autoantigens including Jo-1, PL-7, PL-12, SRP, Mi-2, Ku, PM/Scl and Scl-70) over a 38-month period. 316 myositis dot-blot assays (MSD) were performed in 274 patients (156 women, mean age 53±10.6 years) referring for muscular and/or systemic symptoms suggesting IIM. The timing of dot prescription through the diagnostic process was highly variable: without (35%), concomitantly (16%) or after electromyographic studies (35%). Fifty-nine patients (22%) had IIM according to Bohan and Peter's criteria. Among them, 29 (49%) had positive dot (8 Jo-1, 6 PM-Scl, 5 PL-12, 5 SRP, 2 Mi-2, 2 PL-7 and 1 Ku). Various other diagnoses were performed including 35 autoimmune disease or granulomatosis (12%), 19 inflammatory rheumatic disease (7%), 16 non inflammatory muscular disorders (6%), 10 drug-induced myalgia (4%), 11 infectious myositis (4%). Except 11 borderline SRP results and one transient PM-Scl, MSD was positive only in one case of IIM. Dot allowed clinicians to correct diagnosis in 4 cases and improved the diagnosis of IIM subtypes in 4 cases. This study reflects the interest of myositis dot in the rapid diagnosis process of patients with non-specific muscular symptoms leading to various diagnoses including IIM.

An ecological model using promotores de salud to prevent cardiovascular disease on the US-Mexico border: the HEART project.

PubMed

Balcázar, Hector; Wise, Sherrie; Rosenthal, E Lee; Ochoa, Cecilia; Rodriguez, Jose; Hastings, Diana; Flores, Leticia; Hernandez, Lorraine; Duarte-Gardea, Maria

2012-01-01

To address cardiovascular disease risk factors among Hispanics, a community model of prevention requires a comprehensive approach to community engagement. The objectives of our intervention were to reduce cardiovascular disease risk factors in Hispanics living in 2 low-income areas of El Paso, Texas, and to engage the community in a physical activity and nutrition intervention. Drawing on lessons learned in phase 1 (years 2005-2008) of the HEART Project, we used an iterative, community-based process to develop an intervention based on an ecological framework. New community partners were introduced and community health workers delivered several elements of the intervention, including the curriculum entitled "Mi Corazón, Mi Comunidad" ("MiCMiC" [My Heart, My Community]). We received feedback from the project's Community Health Academy and Leadership Council throughout the development process and established a policy agenda that promotes integration of community health workers into the local and state workforce. Collaboration with 2 new community partners, the YWCA and the Department of Parks and Recreation, were instrumental in the process of community-based participatory research. We enrolled 113 participants in the first cohort; 78% were female, and the mean age was 41 years. More than 50% reported having no health insurance coverage. Seventy-two (60%) participants attended 1 or more promotora-led Su Corazón, Su Vida sessions, and 74 (62%) participants attended 1 or more of the 15 exercise classes. HEART phase 2 includes a multilevel ecological model to address cardiovascular disease risk among Hispanics. Future similarly targeted initiatives can benefit from an ecological approach that also embraces the promotora model.

Tick control: trapping, biocontrol, host management and other alternative strategies

USGS Publications Warehouse

Ginsberg, Howard S.; Edited by Sonenshine, Daniel E.; Roe, R. Michael

2014-01-01

Biology of Ticks is the most comprehensive work on tick biology and tick-borne diseases. This second edition is a multi-authored work, featuring the research and analyses of renowned experts across the globe. Spanning two volumes, the book examines the systematics, biology, structure, ecological adaptations, evolution, genomics and the molecular processes that underpin the growth, development and survival of these important disease-transmitting parasites. Also discussed is the remarkable array of diseases transmitted (or caused) by ticks, as well as modern methods for their control. This book should serve as a modern reference for students, scientists, physicians, veterinarians and other specialists. Volume I covers the biology of the tick and features chapters on tick systematics, tick life cycles, external and internal anatomy, and others dedicated to specific organ systems, specifically, the tick integument, mouthparts and digestive system, salivary glands, waste removal, salivary glands, respiratory system, circulatory system and hemolymph, fat body, the nervous and sensory systems and reproductive systems. Volume II includes chapters on the ecology of non-nidicolous and nidicolous ticks, genetics and genomics (including the genome of the Lyme disease vector Ixodes scapularis) and immunity, including host immune responses to tick feeding and tick-host interactions, as well as the tick's innate immune system that prevents and/or controls microbial infections. Six chapters cover in depth the many diseases caused by the major tick-borne pathogens, including tick-borne protozoa, viruses, rickettsiae of all types, other types of bacteria (e.g., the Lyme disease agent) and diseases related to tick paralytic agents and toxins. The remaining chapters are devoted to tick control using vaccines, acaricides, repellents, biocontrol, and, finally, techniques for breeding ticks in order to develop tick colonies for scientific study.

Network-based prediction and knowledge mining of disease genes.

PubMed

Carson, Matthew B; Lu, Hui

2015-01-01

In recent years, high-throughput protein interaction identification methods have generated a large amount of data. When combined with the results from other in vivo and in vitro experiments, a complex set of relationships between biological molecules emerges. The growing popularity of network analysis and data mining has allowed researchers to recognize indirect connections between these molecules. Due to the interdependent nature of network entities, evaluating proteins in this context can reveal relationships that may not otherwise be evident. We examined the human protein interaction network as it relates to human illness using the Disease Ontology. After calculating several topological metrics, we trained an alternating decision tree (ADTree) classifier to identify disease-associated proteins. Using a bootstrapping method, we created a tree to highlight conserved characteristics shared by many of these proteins. Subsequently, we reviewed a set of non-disease-associated proteins that were misclassified by the algorithm with high confidence and searched for evidence of a disease relationship. Our classifier was able to predict disease-related genes with 79% area under the receiver operating characteristic (ROC) curve (AUC), which indicates the tradeoff between sensitivity and specificity and is a good predictor of how a classifier will perform on future data sets. We found that a combination of several network characteristics including degree centrality, disease neighbor ratio, eccentricity, and neighborhood connectivity help to distinguish between disease- and non-disease-related proteins. Furthermore, the ADTree allowed us to understand which combinations of strongly predictive attributes contributed most to protein-disease classification. In our post-processing evaluation, we found several examples of potential novel disease-related proteins and corresponding literature evidence. In addition, we showed that first- and second-order neighbors in the PPI network could be used to identify likely disease associations. We analyzed the human protein interaction network and its relationship to disease and found that both the number of interactions with other proteins and the disease relationship of neighboring proteins helped to determine whether a protein had a relationship to disease. Our classifier predicted many proteins with no annotated disease association to be disease-related, which indicated that these proteins have network characteristics that are similar to disease-related proteins and may therefore have disease associations not previously identified. By performing a post-processing step after the prediction, we were able to identify evidence in literature supporting this possibility. This method could provide a useful filter for experimentalists searching for new candidate protein targets for drug repositioning and could also be extended to include other network and data types in order to refine these predictions.

A taxonomy for disease management: a scientific statement from the American Heart Association Disease Management Taxonomy Writing Group.

PubMed

Krumholz, Harlan M; Currie, Peter M; Riegel, Barbara; Phillips, Christopher O; Peterson, Eric D; Smith, Renee; Yancy, Clyde W; Faxon, David P

2006-09-26

Disease management has shown great promise as a means of reorganizing chronic care and optimizing patient outcomes. Nevertheless, disease management programs are widely heterogeneous and lack a shared definition of disease management, which limits our ability to compare and evaluate different programs. To address this problem, the American Heart Association's Disease Management Taxonomy Writing Group developed a system of classification that can be used both to categorize and compare disease management programs and to inform efforts to identify specific factors associated with effectiveness. The AHA Writing Group began with a conceptual model of disease management and its components and subsequently validated this model over a wide range of disease management programs. A systematic MEDLINE search was performed on the terms heart failure, diabetes, and depression, together with disease management, case management, and care management. The search encompassed articles published in English between 1987 and 2005. We then selected studies that incorporated (1) interventions designed to improve outcomes and/or reduce medical resource utilization in patients with heart failure, diabetes, or depression and (2) clearly defined protocols with at least 2 prespecified components traditionally associated with disease management. We analyzed the study protocols and used qualitative research methods to develop a disease management taxonomy with our conceptual model as the organizing framework. The final taxonomy includes the following 8 domains: (1) Patient population is characterized by risk status, demographic profile, and level of comorbidity. (2) Intervention recipient describes the primary targets of disease management intervention and includes patients and caregivers, physicians and allied healthcare providers, and healthcare delivery systems. (3) Intervention content delineates individual components, such as patient education, medication management, peer support, or some form of postacute care, that are included in disease management. (4) Delivery personnel describes the network of healthcare providers involved in the delivery of disease management interventions, including nurses, case managers, physicians, pharmacists, case workers, dietitians, physical therapists, psychologists, and information systems specialists. (5) Method of communication identifies a broad range of disease management delivery systems that may include in-person visitation, audiovisual information packets, and some form of electronic or telecommunication technology. (6) Intensity and complexity distinguish between the frequency and duration of exposure, as well as the mix of program components, with respect to the target for disease management. (7) Environment defines the context in which disease management interventions are typically delivered and includes inpatient or hospital-affiliated outpatient programs, community or home-based programs, or some combination of these factors. (8) Clinical outcomes include traditional, frequently assessed primary and secondary outcomes, as well as patient-centered measures, such as adherence to medication, self-management, and caregiver burden. This statement presents a taxonomy for disease management that describes critical program attributes and allows for comparisons across interventions. Routine application of the taxonomy may facilitate better comparisons of structure, process, and outcome measures across a range of disease management programs and should promote uniformity in the design and conduct of studies that seek to validate disease management strategies.

Neuropathology of Alzheimer's disease.

PubMed

Perl, Daniel P

2010-01-01

Alois Alzheimer first pointed out that the disease which would later bear his name has a distinct and recognizable neuropathological substrate. Since then, much has been added to our understanding of the pathological lesions associated with the condition. The 2 primary cardinal lesions associated with Alzheimer's disease are the neurofibrillary tangle and the senile plaque. The neurofibrillary tangle consists of abnormal accumulations of abnormally phosphorylated tau within the perikaryal cytoplasm of certain neurons. The senile plaque consists of a central core of beta-amyloid, a 4-kD peptide, surrounded by abnormally configured neuronal processes or neurites. Other neuropathological lesions are encountered in cases of Alzheimer's disease, but the disease is defined and recognized by these 2 cardinal lesions. Other lesions include poorly understood changes such as granulovacuolar degeneration and eosinophilic rodlike bodies (Hirano bodies). The loss of synaptic components is a change that clearly has a significant impact on cognitive function and represents another important morphological alteration. It is important to recognize that distinguishing between Alzheimer's disease, especially in its early stages, and normal aging may be very difficult, particularly if one is examining the brains of patients who died at an advanced old age. It is also noted that instances of pure forms of Alzheimer's disease, in the absence of other coexistent brain disease processes, such as infarctions or Parkinson's disease-related lesions, are relatively uncommon, and this must be taken into account by researchers who employ postmortem brain tissues for research. (c) 2010 Mount Sinai School of Medicine.

Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

PubMed

Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

2014-09-01

Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

The ecological foundations of transmission potential and vector-borne disease in urban landscapes.

PubMed

LaDeau, Shannon L; Allan, Brian F; Leisnham, Paul T; Levy, Michael Z

2015-07-01

Urban transmission of arthropod-vectored disease has increased in recent decades. Understanding and managing transmission potential in urban landscapes requires integration of sociological and ecological processes that regulate vector population dynamics, feeding behavior, and vector-pathogen interactions in these unique ecosystems. Vectorial capacity is a key metric for generating predictive understanding about transmission potential in systems with obligate vector transmission. This review evaluates how urban conditions, specifically habitat suitability and local temperature regimes, and the heterogeneity of urban landscapes can influence the biologically-relevant parameters that define vectorial capacity: vector density, survivorship, biting rate, extrinsic incubation period, and vector competence.Urban landscapes represent unique mosaics of habitat. Incidence of vector-borne disease in urban host populations is rarely, if ever, evenly distributed across an urban area. The persistence and quality of vector habitat can vary significantly across socio-economic boundaries to influence vector species composition and abundance, often generating socio-economically distinct gradients of transmission potential across neighborhoods.Urban regions often experience unique temperature regimes, broadly termed urban heat islands (UHI). Arthropod vectors are ectothermic organisms and their growth, survival, and behavior are highly sensitive to environmental temperatures. Vector response to UHI conditions is dependent on regional temperature profiles relative to the vector's thermal performance range. In temperate climates UHI can facilitate increased vector development rates while having countervailing influence on survival and feeding behavior. Understanding how urban heat island (UHI) conditions alter thermal and moisture constraints across the vector life cycle to influence transmission processes is an important direction for both empirical and modeling research.There remain persistent gaps in understanding of vital rates and drivers in mosquito-vectored disease systems, and vast holes in understanding for other arthropod vectored diseases. Empirical studies are needed to better understand the physiological constraints and socio-ecological processes that generate heterogeneity in critical transmission parameters, including vector survival and fitness. Likewise, laboratory experiments and transmission models must evaluate vector response to realistic field conditions, including variability in sociological and environmental conditions.

Protection of primary neurons and mouse brain from Alzheimer’s pathology by molecular tweezers

PubMed Central

Attar, Aida; Ripoli, Cristian; Riccardi, Elisa; Maiti, Panchanan; Li Puma, Domenica D.; Liu, Tingyu; Hayes, Jane; Jones, Mychica R.; Lichti-Kaiser, Kristin; Yang, Fusheng; Gale, Greg D.; Tseng, Chi-hong; Tan, Miao; Xie, Cui-Wei; Straudinger, Jeffrey L.; Klärner, Frank-Gerrit; Schrader, Thomas; Frautschy, Sally A.; Grassi, Claudio

2012-01-01

Alzheimer’s disease is a devastating cureless neurodegenerative disorder affecting >35 million people worldwide. The disease is caused by toxic oligomers and aggregates of amyloid β protein and the microtubule-associated protein tau. Recently, the Lys-specific molecular tweezer CLR01 has been shown to inhibit aggregation and toxicity of multiple amyloidogenic proteins, including amyloid β protein and tau, by disrupting key interactions involved in the assembly process. Following up on these encouraging findings, here, we asked whether CLR01 could protect primary neurons from Alzheimer’s disease-associated synaptotoxicity and reduce Alzheimer’s disease–like pathology in vivo. Using cell culture and brain slices, we found that CLR01 effectively inhibited synaptotoxicity induced by the 42-residue isoform of amyloid β protein, including ∼80% inhibition of changes in dendritic spines density and long-term potentiation and complete inhibition of changes in basal synaptic activity. Using a radiolabelled version of the compound, we found that CLR01 crossed the mouse blood–brain barrier at ∼2% of blood levels. Treatment of 15-month-old triple-transgenic mice for 1 month with CLR01 resulted in a decrease in brain amyloid β protein aggregates, hyperphosphorylated tau and microglia load as observed by immunohistochemistry. Importantly, no signs of toxicity were observed in the treated mice, and CLR01 treatment did not affect the amyloidogenic processing of amyloid β protein precursor. Examining induction or inhibition of the cytochrome P450 metabolism system by CLR01 revealed minimal interaction. Together, these data suggest that CLR01 is safe for use at concentrations well above those showing efficacy in mice. The efficacy and toxicity results support a process-specific mechanism of action of molecular tweezers and suggest that these are promising compounds for developing disease-modifying therapy for Alzheimer’s disease and related disorders. PMID:23183235

Redesigning the care of fragility fracture patients to improve osteoporosis management: a health care improvement project.

PubMed

Harrington, J Timothy; Barash, Harvey L; Day, Sherry; Lease, Joellen

2005-04-15

To develop new processes that assure more reliable, population-based care of fragility fracture patients. A 4-year clinical improvement project was performed in a multispecialty, community practice health system using evidence-based guidelines and rapid cycle process improvement methods (plan-do-study-act cycles). Prior to this project, appropriate osteoporosis care was provided to only 5% of our 1999 hip fracture patients. In 2001, primary physicians were provided prompts about appropriate care (cycle 1), which resulted in improved care for only 20% of patients. A process improvement pilot in 2002 (cycle 2) and full program implementation in 2003 (cycle 3) have assured osteoporosis care for all willing and able patients with any fragility fracture. Altogether, 58% of 2003 fragility fracture patients, including 46% of those with hip fracture, have had a bone measurement, have been assigned to osteoporosis care with their primary physician or a consultant, and are being monitored regularly. Only 19% refused osteoporosis care. Key process improvements have included using orthopedic billings to identify patients, referring patients directly from orthopedics to an osteoporosis care program, organizing care with a nurse manager and process management computer software, assigning patients to primary or consultative physician care based on disease severity, and monitoring adherence to therapy by telephone. Reliable osteoporosis care is achievable by redesigning clinical processes. Performance data motivate physicians to reconsider traditional approaches. Improving the care of osteoporosis and other chronic diseases requires coordinated care across specialty boundaries and health system support.

Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.

PubMed

Saketkoo, Lesley Ann; Mittoo, Shikha; Frankel, Sid; LeSage, Daphne; Sarver, Catherine; Phillips, Kristine; Strand, Vibeke; Matteson, Eric L

2014-04-01

Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.

Alcohol's Effects on the Cardiovascular System.

PubMed

Piano, Mariann R

2017-01-01

Alcohol use has complex effects on cardiovascular (CV) health. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Although many behavioral, genetic, and biologic variants influence the interconnection between alcohol use and CV disease, dose and pattern of alcohol consumption seem to modulate this most. Low-to-moderate alcohol use may mitigate certain mechanisms such as risk and hemostatic factors affecting atherosclerosis and inflammation, pathophysiologic processes integral to most CV disease. But any positive aspects of drinking must be weighed against serious physiological effects, including mitochondrial dysfunction and changes in circulation, inflammatory response, oxidative stress, and programmed cell death, as well as anatomical damage to the CV system, especially the heart itself. Both the negative and positive effects of alcohol use on particular CV conditions are presented here. The review concludes by suggesting several promising avenues for future research related to alcohol use and CV disease. These include using direct biomarkers of alcohol to confirm self-report of alcohol consumption levels; studying potential mediation of various genetic, socioeconomic, and racial and ethnic factors that may affect alcohol use and CV disease; reviewing alcohol-medication interactions in cardiac patients; and examining CV effects of alcohol use in young adults and in older adults.

Alcohol’s Effects on the Cardiovascular System

PubMed Central

Piano, Mariann R.

2017-01-01

Alcohol use has complex effects on cardiovascular (CV) health. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Although many behavioral, genetic, and biologic variants influence the interconnection between alcohol use and CV disease, dose and pattern of alcohol consumption seem to modulate this most. Low-to-moderate alcohol use may mitigate certain mechanisms such as risk and hemostatic factors affecting atherosclerosis and inflammation, pathophysiologic processes integral to most CV disease. But any positive aspects of drinking must be weighed against serious physiological effects, including mitochondrial dysfunction and changes in circulation, inflammatory response, oxidative stress, and programmed cell death, as well as anatomical damage to the CV system, especially the heart itself. Both the negative and positive effects of alcohol use on particular CV conditions are presented here. The review concludes by suggesting several promising avenues for future research related to alcohol use and CV disease. These include using direct biomarkers of alcohol to confirm self-report of alcohol consumption levels; studying potential mediation of various genetic, socioeconomic, and racial and ethnic factors that may affect alcohol use and CV disease; reviewing alcohol–medication interactions in cardiac patients; and examining CV effects of alcohol use in young adults and in older adults. PMID:28988575

Excessive daytime sleepiness in Parkinson disease: a SPECT study.

PubMed

Matsui, Hideaki; Nishinaka, Kazuto; Oda, Masaya; Hara, Narihiro; Komatsu, Kenichi; Kubori, Tamotsu; Udaka, Fukashi

2006-07-01

The underlying pathologic mechanism of excessive daytime sleepiness (EDS) in Parkinson disease and the relative contributions of brain function to this process are poorly understood. We compared brain perfusion images between patients with Parkinson disease and EDS and those without EDS using n-isopropyl-p-1231 iodoamphetamine single photon emission computed tomography. Clinical study. Sumitomo Hospital. Thirteen patients with Parkinson disease with EDS (EDS group) and 27 patients with Parkinson disease without EDS (no-EDS group) were studied. Whether or not each case had EDS was determined according to the response to the Epworth Sleepiness Scale: patients with an Epworth Sleepiness Scale score > or = 10 were included in the EDS group, and patients with an Epworth Sleepiness Scale score < or = 9 were included in the no-EDS group. There were significant hypoperfusions in the left parietal and temporal association cortex in the EDS group. In the multivariable logistic regression model, attention and decreased regional cerebral blood flow of the left parietal association cortex and right caudate and increased regional cerebral blood flow of the right thalamus were the independent and significant factors. The cortical hypofunction relative to hyperfunction of the brain stem may relate to EDS in Parkinson disease. This is the first imaging study about EDS in Parkinson disease, and further studies are required.

Neural correlates of impaired emotion processing in manifest Huntington's disease.

PubMed

Dogan, Imis; Saß, Christian; Mirzazade, Shahram; Kleiman, Alexandra; Werner, Cornelius J; Pohl, Anna; Schiefer, Johannes; Binkofski, Ferdinand; Schulz, Jörg B; Shah, N Jon; Reetz, Kathrin

2014-05-01

The complex phenotype of Huntington's disease (HD) encompasses motor, psychiatric and cognitive dysfunctions, including early impairments in emotion recognition. In this first functional magnetic resonance imaging study, we investigated emotion-processing deficits in 14 manifest HD patients and matched controls. An emotion recognition task comprised short video clips displaying one of six basic facial expressions (sadness, happiness, disgust, fear, anger and neutral). Structural changes between patients and controls were assessed by means of voxel-based morphometry. Along with deficient recognition of negative emotions, patients exhibited predominantly lower neural response to stimuli of negative valences in the amygdala, hippocampus, striatum, insula, cingulate and prefrontal cortices, as well as in sensorimotor, temporal and visual areas. Most of the observed reduced activity patterns could not be explained merely by regional volume loss. Reduced activity in the thalamus during fear correlated with lower thalamic volumes. During the processing of sadness, patients exhibited enhanced amygdala and hippocampal activity along with reduced recruitment of the medial prefrontal cortex. Higher amygdala activity was related to more pronounced amygdala atrophy and disease burden. Overall, the observed emotion-related dysfunctions in the context of structural neurodegeneration suggest both disruptions of striatal-thalamo-cortical loops and potential compensation mechanism with greater disease severity in manifest HD.

An exploration of mothers' and fathers' views of their identities in chronic-kidney-disease management: parents as students?

PubMed

Swallow, Veronica

2008-12-01

To explore parents' views of their identities as they learn to manage their child's chronic kidney disease. Parents are expected to participate in management and usually learn necessary skills from the multidisciplinary team. Research highlights the importance of professionals defining parents' management roles in chronic disease; but little is known about parents' views on their own identities as the complex and dynamic process of teaching and learning unfolds around their child's condition. According to positioning theory, identity development is a dynamic and fluid process that occurs during interaction, with each person positioning themselves while simultaneously positioning the other person, yet this concept has not been considered in relation to parents' contributions to disease management. A longitudinal, grounded theory study conducted in a UK Children's Kidney Unit. This paper focuses on one aspect of a larger study exploring family learning in disease management. Six mothers and two fathers of six children with a recently diagnosed chronic kidney disease participated in a total of 21 semi-structured interviews during the 18 months after referral to the unit. Interviews included discussion about the parts they played in relation to professionals during the management process. Findings were interpreted within a framework of positioning theory. Parents participated in teaching/learning/assessment that was both planned (involving allocated clinical lessons and tasks) and spontaneous (in response to current situations), to facilitate their participation. They positioned multidisciplinary team members as teachers as well as professionals, simultaneously positioning themselves as students as well as parents. Parents' clinical duties and obligations are not an automatic part of parenting but become part of the broader process of sharing disease management, this can lead to them assuming the additional identity of a 'student'. Involving parents in ongoing discussions about their positions in management may help promote their active and informed participation.

Introduction of New Vaccines: Decision-making Process in Bangladesh

PubMed Central

Sarma, Haribondhu; Bari, Tajul I.; Koehlmoos, Tracey P.

2013-01-01

The understanding of the decision-making process in the introduction of new vaccines helps establish why vaccines are adopted or not. It also contributes to building a sustainable demand for vaccines in a country. The purpose of the study was to map and analyze the formal decision-making process in relation to the introduction of new vaccines within the context of health policy and health systems and identify the ways of making decisions to introduce new vaccines in Bangladesh. During February-April 2011, a qualitative assessment was made at the national level to evaluate the decision-making process around the adoption of new vaccines in Bangladesh. The study population included: policy-level people, programme heads or associates, and key decision-makers of the Government, private sector, non-governmental organizations, and international agencies at the national level. In total, 13 key informants were purposively selected. Data were collected by interviewing key informants and reviewing documents. Data were analyzed thematically. The findings revealed that the actors from different sectors at the policy level were involved in the decision-making process in the introduction of new vaccines. They included policy-makers from the ministries of health and family welfare, finance, and local government and rural development; academicians; researchers; representatives from professional associations; development partners; and members of different committees on EPI. They contributed to the introduction of new vaccines in their own capacity. The burden of disease, research findings on vaccine-preventable diseases, political issues relating to outbreaks of certain diseases, initiatives of international and local stakeholders, pressure of development partners, the Global Alliance for Vaccines and Immunization (GAVI) support, and financial matters were the key factors in the introduction of new vaccines in Bangladesh. The slow introduction and uptake of new vaccines is a concern in the country. Rapid action on the application of GAVI support and less time taken by the Government in processing the implementation and administrative work may expedite the introduction of new vaccines in future in this country. PMID:23930339

Introduction of new vaccines: decision-making process in Bangladesh.

PubMed

Uddin, Jasim; Sarma, Haribondhu; Bari, Tajul I; Koehlmoos, Tracey P

2013-06-01

The understanding of the decision-making process in the introduction of new vaccines helps establish why vaccines are adopted or not. It also contributes to building a sustainable demand for vaccines in a country. The purpose of the study was to map and analyze the formal decision-making process in relation to the introduction of new vaccines within the context of health policy and health systems and identify the ways of making decisions to introduce new vaccines in Bangladesh. During February-April 2011, a qualitative assessment was made at the national level to evaluate the decision-making process around the adoption of new vaccines in Bangladesh. The study population included: policy-level people, programme heads or associates, and key decision-makers of the Government, private sector, non-governmental organizations, and international agencies at the national level. In total, 13 key informants were purposively selected. Data were collected by interviewing key informants and reviewing documents. Data were analyzed thematically. The findings revealed that the actors from different sectors at the policy level were involved in the decision-making process in the introduction of new vaccines. They included policy-makers from the ministries of health and family welfare, finance, and local government and rural development; academicians; researchers; representatives from professional associations; development partners; and members of different committees on EPI. They contributed to the introduction of new vaccines in their own capacity. The burden of disease, research findings on vaccine-preventable diseases, political issues relating to outbreaks of certain diseases, initiatives of international and local stakeholders, pressure of development partners, the Global Alliance for Vaccines and Immunization (GAVI) support, and financial matters were the key factors in the introduction of new vaccines in Bangladesh. The slow introduction and uptake of new vaccines is a concern in the country. Rapid action on the application of GAVI support and less time taken by the Government in processing the implementation and administrative work may expedite the introduction of new vaccines in future in this country.

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.

Multiparametric Imaging of Organ System Interfaces

PubMed Central

Vandoorne, Katrien; Nahrendorf, Matthias

2017-01-01

Cardiovascular diseases are a consequence of genetic and environmental risk factors that together generate arterial wall and cardiac pathologies. Blood vessels connect multiple systems throughout the entire body and allow organs to interact via circulating messengers. These same interactions facilitate nervous and metabolic system influence on cardiovascular health. Multiparametric imaging offers the opportunity to study these interfacing systems’ distinct processes, to quantify their interactions and to explore how these contribute to cardiovascular disease. Noninvasive multiparametric imaging techniques are emerging tools that can further our understanding of this complex and dynamic interplay. PET/MRI and multichannel optical imaging are particularly promising because they can simultaneously sample multiple biomarkers. Preclinical multiparametric diagnostics could help discover clinically relevant biomarker combinations pivotal for understanding cardiovascular disease. Interfacing systems important to cardiovascular disease include the immune, nervous and hematopoietic systems. These systems connect with ‘classical’ cardiovascular organs, like the heart and vasculature, and with the brain. The dynamic interplay between these systems and organs enables processes such as hemostasis, inflammation, angiogenesis, matrix remodeling, metabolism and fibrosis. As the opportunities provided by imaging expand, mapping interconnected systems will help us decipher the complexity of cardiovascular disease and monitor novel therapeutic strategies. PMID:28360260

Using hyperspectral imaging technology to identify diseased tomato leaves

NASA Astrophysics Data System (ADS)

Li, Cuiling; Wang, Xiu; Zhao, Xueguan; Meng, Zhijun; Zou, Wei

2016-11-01

In the process of tomato plants growth, due to the effect of plants genetic factors, poor environment factors, or disoperation of parasites, there will generate a series of unusual symptoms on tomato plants from physiology, organization structure and external form, as a result, they cannot grow normally, and further to influence the tomato yield and economic benefits. Hyperspectral image usually has high spectral resolution, not only contains spectral information, but also contains the image information, so this study adopted hyperspectral imaging technology to identify diseased tomato leaves, and developed a simple hyperspectral imaging system, including a halogen lamp light source unit, a hyperspectral image acquisition unit and a data processing unit. Spectrometer detection wavelength ranged from 400nm to 1000nm. After hyperspectral images of tomato leaves being captured, it was needed to calibrate hyperspectral images. This research used spectrum angle matching method and spectral red edge parameters discriminant method respectively to identify diseased tomato leaves. Using spectral red edge parameters discriminant method produced higher recognition accuracy, the accuracy was higher than 90%. Research results have shown that using hyperspectral imaging technology to identify diseased tomato leaves is feasible, and provides the discriminant basis for subsequent disease control of tomato plants.

Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation.

PubMed Central

Liu, Bin; Gao, Hui-Ming; Hong, Jau-Shyong

2003-01-01

Idiopathic Parkinson's disease (PD) is a devastating movement disorder characterized by selective degeneration of the nigrostriatal dopaminergic pathway. Neurodegeneration usually starts in the fifth decade of life and progresses over 5-10 years before reaching the fully symptomatic disease state. Despite decades of intense research, the etiology of sporadic PD and the mechanism underlying the selective neuronal loss remain unknown. However, the late onset and slow-progressing nature of the disease has prompted the consideration of environmental exposure to agrochemicals, including pesticides, as a risk factor. Moreover, increasing evidence suggests that early-life occurrence of inflammation in the brain, as a consequence of either brain injury or exposure to infectious agents, may play a role in the pathogenesis of PD. Most important, there may be a self-propelling cycle of inflammatory process involving brain immune cells (microglia and astrocytes) that drives the slow yet progressive neurodegenerative process. Deciphering the molecular and cellular mechanisms governing those intricate interactions would significantly advance our understanding of the etiology and pathogenesis of PD and aid the development of therapeutic strategies for the treatment of the disease. PMID:12826478

The effectiveness and efficiency of disease management programs for patients with chronic diseases.

PubMed

Hisashige, Akinori

2012-11-26

Disease management (DM) approach is increasingly advocated as a means of improving effectiveness and efficiency of healthcare for chronic diseases. To evaluate the evidence on effectiveness and efficiency of DM, evidence synthesis was carried out. To locate eligible meta-analyses and systematic reviews, we searched Medline, EMBASE, the Cochrane Library, SCI-EXPANDED, SSCI, A&HCI, DARE, HTA and NHS EED from 1995 to 2010. Two reviewers independently extracted data and assessed a study quality. Twenty-eight meta-analyses and systematic reviews were included for synthesizing evidence. The proportion of articles which observed improvement with a reasonable amount of evidence was the highest at process (69%), followed by health services (63%), QOL (57%), health outcomes (51%), satisfaction (50%), costs (38%) and so on. As to mortality, statistically significant results were observed only in coronary heart disease. Important components in DM, such as a multidisciplinary approach, were identified. The evidence synthesized shows considerable evidence in the effectiveness and efficiency of DM programs in process, health services, QOL and so on. The question is no longer whether DM programs work, but rather which type or component of DM programs works best and efficiently in the context of each healthcare system or country.

The Danger Model Approach to the Pathogenesis of the Rheumatic Diseases

PubMed Central

Pacheco-Tena, César; González-Chávez, Susana Aideé

2015-01-01

The danger model was proposed by Polly Matzinger as complement to the traditional self-non-self- (SNS-) model to explain the immunoreactivity. The danger model proposes a central role of the tissular cells' discomfort as an element to prime the immune response processes in opposition to the traditional SNS-model where foreignness is a prerequisite. However recent insights in the proteomics of diverse tissular cells have revealed that under stressful conditions they have a significant potential to initiate, coordinate, and perpetuate autoimmune processes, in many cases, ruling over the adaptive immune response cells; this ruling potential can also be confirmed by observations in several genetically manipulated animal models. Here, we review the pathogenesis of rheumatic diseases such as systemic lupus erythematous, rheumatoid arthritis, spondyloarthritis including ankylosing spondylitis, psoriasis, and Crohn's disease and provide realistic approaches based on the logic of the danger model. We assume that tissular dysfunction is a prerequisite for chronic autoimmunity and propose two genetically conferred hypothetical roles for the tissular cells causing the disease: (A) the Impaired cell and (B) the paranoid cell. Both roles are not mutually exclusive. Some examples in human disease and in animal models are provided based on current evidence. PMID:25973436

Chagas disease drug discovery: toward a new era.

PubMed

Chatelain, Eric

2015-01-01

American trypanosomiasis, or Chagas disease, is the result of infection by the Trypanosoma cruzi parasite. Endemic in Latin America where it is the major cause of death from cardiomyopathy, the impact of the disease is reaching global proportions through migrating populations. New drugs that are safe, efficacious, low cost, and adapted to the field are critically needed. Over the past five years, there has been increased interest in the disease and a surge in activities within various organizations. However, recent clinical trials with azoles, specifically posaconazole and the ravuconazole prodrug E1224, were disappointing, with treatment failure in Chagas patients reaching 70% to 90%, as opposed to 6% to 30% failure for benznidazole-treated patients. The lack of translation from in vitro and in vivo models to the clinic observed for the azoles raises several questions. There is a scientific requirement to review and challenge whether we are indeed using the right tools and decision-making processes to progress compounds forward for the treatment of this disease. New developments in the Chagas field, including new technologies and tools now available, will be discussed, and a redesign of the current screening strategy during the discovery process is proposed. © 2014 Society for Laboratory Automation and Screening.

Understanding uncertainty in temperature effects on vector-borne disease: a Bayesian approach

USGS Publications Warehouse

Johnson, Leah R.; Ben-Horin, Tal; Lafferty, Kevin D.; McNally, Amy; Mordecai, Erin A.; Paaijmans, Krijn P.; Pawar, Samraat; Ryan, Sadie J.

2015-01-01

Extrinsic environmental factors influence the distribution and population dynamics of many organisms, including insects that are of concern for human health and agriculture. This is particularly true for vector-borne infectious diseases like malaria, which is a major source of morbidity and mortality in humans. Understanding the mechanistic links between environment and population processes for these diseases is key to predicting the consequences of climate change on transmission and for developing effective interventions. An important measure of the intensity of disease transmission is the reproductive number R0. However, understanding the mechanisms linking R0 and temperature, an environmental factor driving disease risk, can be challenging because the data available for parameterization are often poor. To address this, we show how a Bayesian approach can help identify critical uncertainties in components of R0 and how this uncertainty is propagated into the estimate of R0. Most notably, we find that different parameters dominate the uncertainty at different temperature regimes: bite rate from 15°C to 25°C; fecundity across all temperatures, but especially ~25–32°C; mortality from 20°C to 30°C; parasite development rate at ~15–16°C and again at ~33–35°C. Focusing empirical studies on these parameters and corresponding temperature ranges would be the most efficient way to improve estimates of R0. While we focus on malaria, our methods apply to improving process-based models more generally, including epidemiological, physiological niche, and species distribution models.

Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease

PubMed Central

Horseman, Michael A.; Surani, Salim; Bowman, John D.

2017-01-01

Background: Endotoxin is a lipopolysaccharide (LPS) constituent of the outer membrane of most gram negative bacteria. Ubiquitous in the environment, it has been implicated as a cause or con-tributing factor in several disparate disorders from sepsis to heatstroke and Type II diabetes mellitus. Starting at birth, the innate immune system develops cellular defense mechanisms against environmen-tal microbes that are in part modulated through a series of receptors known as toll-like receptors. Endo-toxin, often referred to as LPS, binds to toll-like receptor 4 (TLR4)/ myeloid differentiation protein 2 (MD2) complexes on various tissues including cells of the innate immune system, smooth muscle and endothelial cells of blood vessels including coronary arteries, and adipose tissue. Entry of LPS into the systemic circulation ultimately leads to intracellular transcription of several inflammatory mediators. The subsequent inflammation has been implicated in the development and progression atherosclerosis and subsequent coronary artery disease and heart failure. Objective: The potential roles of endotoxin and TLR4 are reviewed regarding their role in the pathogen-esis of atherosclerotic heart disease. Conclusion: Atherosclerosis is initiated by inflammation in arterial endothelial and subendothelial cells, and inflammatory processes are implicated in its progression to clinical heart disease. Endotoxin and TLR4 play a central role in the inflammatory process, and represent potential targets for therapeutic intervention. Therapy with HMG-CoA inhibitors may reduce the expression of TLR4 on monocytes. Other therapeutic interventions targeting TLR4 expression or function may prove beneficial in athero-sclerotic disease prevention and treatment.

Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases.

PubMed

Martin-Jiménez, Cynthia A; García-Vega, Ángela; Cabezas, Ricardo; Aliev, Gjumrakch; Echeverria, Valentina; González, Janneth; Barreto, George E

2017-11-01

Endoplasmic reticulum (ER) is a subcellular organelle involved in protein folding and processing. ER stress constitutes a cellular process characterized by accumulation of misfolded proteins, impaired lipid metabolism and induction of inflammatory responses. ER stress has been suggested to be involved in several human pathologies, including neurodegenerative diseases and obesity. Different studies have shown that both neurodegenerative diseases and obesity trigger similar cellular responses to ER stress. Moreover, both diseases are assessed in astrocytes as evidences suggest these cells as key regulators of brain homeostasis. However, the exact contributions to the effects of ER stress in astrocytes in the various neurodegenerative diseases and its relation with obesity are not well known. Here, we discuss recent advances in the understanding of molecular mechanisms that regulate ER stress-related disorders in astrocytes such as obesity and neurodegeneration. Moreover, we outline the correlation between the activated proteins of the unfolded protein response (UPR) in these pathological conditions in order to identify possible therapeutic targets for ER stress in astrocytes. We show that ER stress in astrocytes shares UPR activation pathways during both obesity and neurodegenerative diseases, demonstrating that UPR related proteins like ER chaperone GRP 78/Bip, PERK pathway and other exogenous molecules ameliorate UPR response and promote neuroprotection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dupuytren's: a systems biology disease

PubMed Central

2011-01-01

Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder of the palm of the hands leading to digital contracture. DD commonly occurs in individuals of northern European extraction. Cellular components and processes associated with DD pathogenesis include altered gene and protein expression of cytokines, growth factors, adhesion molecules, and extracellular matrix components. Histology has shown increased but varying levels of particular types of collagen, myofibroblasts and myoglobin proteins in DD tissue. Free radicals and localised ischaemia have been suggested to trigger the proliferation of DD tissue. Although the existing available biological information on DD may contain potentially valuable (though largely uninterpreted) information, the precise aetiology of DD remains unknown. Systems biology combines mechanistic modelling with quantitative experimentation in studies of networks and better understanding of the interaction of multiple components in disease processes. Adopting systems biology may be the ideal approach for future research in order to improve understanding of complex diseases of multifactorial origin. In this review, we propose that DD is a disease of several networks rather than of a single gene, and show that this accounts for the experimental observations obtained to date from a variety of sources. We outline how DD may be investigated more effectively by employing a systems biology approach that considers the disease network as a whole rather than focusing on any specific single molecule. PMID:21943049

Proteomic Analysis of the Human Olfactory Bulb.

PubMed

Dammalli, Manjunath; Dey, Gourav; Madugundu, Anil K; Kumar, Manish; Rodrigues, Benvil; Gowda, Harsha; Siddaiah, Bychapur Gowrishankar; Mahadevan, Anita; Shankar, Susarla Krishna; Prasad, Thottethodi Subrahmanya Keshava

2017-08-01

The importance of olfaction to human health and disease is often underappreciated. Olfactory dysfunction has been reported in association with a host of common complex diseases, including neurological diseases such as Alzheimer's disease and Parkinson's disease. For health, olfaction or the sense of smell is also important for most mammals, for optimal engagement with their environment. Indeed, animals have developed sophisticated olfactory systems to detect and interpret the rich information presented to them to assist in day-to-day activities such as locating food sources, differentiating food from poisons, identifying mates, promoting reproduction, avoiding predators, and averting death. In this context, the olfactory bulb is a vital component of the olfactory system receiving sensory information from the axons of the olfactory receptor neurons located in the nasal cavity and the first place that processes the olfactory information. We report in this study original observations on the human olfactory bulb proteome in healthy subjects, using a high-resolution mass spectrometry-based proteomic approach. We identified 7750 nonredundant proteins from human olfactory bulbs. Bioinformatics analysis of these proteins showed their involvement in biological processes associated with signal transduction, metabolism, transport, and olfaction. These new observations provide a crucial baseline molecular profile of the human olfactory bulb proteome, and should assist the future discovery of biomarker proteins and novel diagnostics associated with diseases characterized by olfactory dysfunction.

Stress, depression, and cardiovascular dysregulation: A review of neurobiological mechanisms and the integration of research from preclinical disease models

PubMed Central

Grippo, Angela J.; Johnson, Alan Kim

2008-01-01

A bidirectional association between mood disorders such as depression, and cardiovascular diseases such as myocardial infarction and congestive heart failure, has been described; however, the precise neurobiological mechanisms that underlie these associations have not been fully elucidated. This review is focused on the neurobiological processes and mediators that are common to both mood and cardiovascular disorders, with an emphasis on the role of exogenous stressors in addition to: (a) neuroendocrine and neurohumoral changes involving dysfunction of the hypothalamic-pituitary-adrenal axis and activation of the renin-angiotensin-aldosterone system, (b) immune alterations including activation of pro-inflammatory cytokines, (c) autonomic and cardiovascular dysregulation including increased sympathetic drive, withdrawal of parasympathetic tone, cardiac rate and rhythm disturbances, and altered baroreceptor reflex function, (d) central neurotransmitter system dysfunction including dopamine, norepinephrine and serotonin, and (e) behavioral changes including fatigue and physical inactivity. We also focus specifically on experimental investigations with preclinical disease models, conducted to elucidate the neurobiological mechanisms underlying the link between mood disorders and cardiovascular disease. These include: (a) the chronic mild stress model of depression, (b) a model of congestive heart failure, a model of cardiovascular deconditioning, (d) pharmacological manipulations of body fluid and sodium balance, and (e) pharmacological manipulations of the central serotonergic system. In combination with the extensive literature describing findings from human research, the investigation of mechanisms underlying mood and cardiovascular regulation using animal models will enhance our understanding of the association of depression and cardiovascular disease, and can promote the development of better treatments and interventions for individuals with these co-morbid conditions. PMID:19116888

Medical History as an Introduction to Clinical Reasoning.

ERIC Educational Resources Information Center

Maulitz, Russell C.; And Others

1983-01-01

An elective course in the history of medicine focuses on clinical thinking using the case study method. Course goals include: student recognition of clinical reasoning as a historical process; understanding of distinctions between disease categories and etiological frameworks; and different conceptualizations (etiological and syndromic) of…

A MULTIPLE-PURPOSE DESIGN APPROACH TO THE EVALUATION OF RISKS FROM COMPLEX MIXTURES OF DISINFECTION BY-PRODUCTS

EPA Science Inventory

Drinking water disinfection has effectively eliminated much of the morbidity and mortality associated with waterborne infectious diseases in the United States. Various disinfection processes, however, produce certain types and amounts of disinfection by-products (DBPs), including...

Implications of the Institute of Medicine Report: Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease.

PubMed

Wagner, J A; Ball, J R

2015-07-01

The Institute of Medicine (IOM) released a groundbreaking 2010 report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease. Key recommendations included a harmonized scientific process and a general framework for biomarker evaluation with three interrelated steps: (1) Analytical validation -- is the biomarker measurement accurate? (2) Qualification -- is the biomarker associated with the clinical endpoint of concern? (3) Utilization -- what is the specific context of the proposed use? © 2015 American Society for Clinical Pharmacology and Therapeutics.