Sample records for developing effective chronic

  1. Siblings of children with a chronic illness: a meta-analysis.

    PubMed

    Sharpe, Donald; Rossiter, Lucille

    2002-12-01

    To review the literature pertaining to the siblings of children with a chronic illness. Fifty-one published studies and 103 effect sizes were identified and examined through meta-analysis. We found (1) a modest, negative effect size statistic existed for siblings of children with a chronic illness relative to comparison participants or normative data; (2) heterogeneity existed for those effect sizes; (3) parent reports were more negative than child self-reports; (4) psychological functioning (i.e., depression, anxiety), peer activities, and cognitive development scores were lower for siblings of children with a chronic illness compared to controls; and (5) a cluster of chronic illnesses with daily treatment regimes was associated with negative effect statistics compared to chronic illnesses that did not affect daily functioning. More methodologically sound studies investigating the psychological functioning of siblings of children with a chronic illness are needed. Clinicians need to know that siblings of children with a chronic illness are at risk for negative psychological effects. Intervention programs for the siblings and families of children with a chronic illness should be developed.

  2. [The development of therapeutic vaccine for hepatitis C virus].

    PubMed

    Kimura, Kiminori; Kohara, Michinori

    2012-10-01

    Chronic hepatitis C caused by infection with the hepatitis C virus(HCV)is a global health problem. HCV causes persistent infection that can lead to chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The therapeutic efficacy of antiviral drugs is not optimal in patients with chronic infection; furthermore, an effective vaccine has not yet been developed. To design an effective HCV vaccine, generation of a convenient animal model of HCV infection is necessary. Recently, we used the Cre/loxP switching system to generate an immunocompetent mouse model of HCV expression, thereby enabling the study of host immune responses against HCV proteins. At present vaccine has not yet been shown to be therapeutically effective against chronic HCV infection. We examined the therapeutic effects of a recombinant vaccinia virus(rVV)encoding HCV protein in a mouse model. we generated rVVs for 3 different HCV proteins and found that one of the recombinant viruses encoding a nonstructural protein(rVV-N25)resolved pathological chronic hepatitis C symptoms in the liver. We propose the possibility that rVV-N25 immunization has the potential for development of an effective therapeutic vaccine for HCV induced chronic hepatitis. The utilization of the therapeutic vaccine can protect progress to chronic hepatitis, and as a consequence, leads to eradication of hepatocellular carcinoma. In this paper, we summarized our current study for HCV therapeutic vaccine and review the vaccine development to date.

  3. ACUTE TO CHRONIC ESTIMATION SOFTWARE FOR WINDOWS

    EPA Science Inventory

    Chronic No-Observed Effect Concentrations (NOEC) are commonly determined by either using acute-to-chronic ratios or by performing an ANOVA on chronic test data; both require lengthy and expensive chronic test results. Acute-to-Chronic Estimation (ACE) software was developed to p...

  4. Chronic neglect and aggression/delinquency: A longitudinal examination.

    PubMed

    Logan-Greene, Patricia; Semanchin Jones, Annette

    2015-07-01

    Neglect is the most common form of maltreatment in the United States, yet its impact on development remains understudied, especially for chronic neglect. Chronic neglect is also one of the most costly burdens on child welfare systems. This study examines the effects of chronic neglect, including two subtypes (Failure to Provide and Lack of Supervision) on adolescent aggression and delinquency using a diverse longitudinal sample of youth. Chronic neglect and chronic failure to provide (ages 0-12) predicted aggression/delinquency (age 14) even after controlling for the effects of other maltreatment (ages 0-12). Chronic lack of supervision, however, did not. Gender significantly moderated these effects, suggesting that males are more likely to respond to neglect by becoming aggressive/delinquent. Finally, social problems (age 12) partially mediated for boys, and fully mediated for girls, the connections between chronic neglect and aggression/delinquency, bolstering theorizing that neglect impairs social functioning broadly. Implications include the need for further research on chronic neglect, especially in providing guidance for child welfare systems. Interventions for chronically neglected youth should include social skill development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. [Vaccine might be an important means of chronic disease prevention and control].

    PubMed

    Zhao, Wenhua; Yang, Weizhong

    2015-08-01

    The vaccine has played an important role in the struggle between human and infectious disease. However, with the development of society and economy, the non-communicable chronic disease has become the biggest threat to human health. The occurrence and development of chronic diseases is related to various factors. Whether vaccines to prevent chronic disease can be developed remains exploratory, while evidence revealing that there exists an important relationship between infection factors and chronic diseases is increasing. Therefore, the vaccine to prevent infection might become one of the most important means to effectively prevent and control chronic diseases.

  6. Acute and chronic effects of the insecticide endrin on renal function and renal hemodynamics.

    DOT National Transportation Integrated Search

    1963-10-01

    Chronic and acute effects of the insecticide endrin on renal function were studied in dogs. Animals were exposed to endrin chronically by intramuscular injection and acutely by intravenous infusion. In acute studies dogs developed systemic hypertensi...

  7. Responding to Students' Chronic Illnesses

    ERIC Educational Resources Information Center

    Shaw, Steven R.; Glaser, Sarah E.; Stern, Melissa; Sferdenschi, Corina; McCabe, Paul C.

    2010-01-01

    Chronic illnesses are long-term or permanent medical conditions that have recurring effects on everyday life. Large and growing number of students have chronic illnesses that affect their emotional development, physical development, academic performance, and family interactions. The primary error in educating those students is assuming that the…

  8. Chronic Disease and Childhood Development: Kidney Disease and Transplantation.

    ERIC Educational Resources Information Center

    Klein, Susan D.; Simmons, Roberta G.

    As part of a larger study of transplantation and chronic disease and the family, 124 children (10-18 years old) who were chronically ill with kidney disease (n=72) or were a year or more post-transplant (n=52) were included in a study focusing on the effects of chronic kidney disease and transplantation on children's psychosocial development. Ss…

  9. Development of the larval amphibian growth and development assay: Effects of chronic 4-tert-octylphenol or 17ß-trenbolone exposure in Xenopus laevis from embryo to juvenile

    EPA Science Inventory

    The Larval Amphibian Growth and Development Assay (LAGDA) is a Tier II test guideline being developed by the US Environmental Protection Agency under the Endocrine Disruptor Screening Program. The LAGDA was designed to evaluate effects of chronic chemical exposure on growth, thy...

  10. Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

    PubMed Central

    Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

    2012-01-01

    Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

  11. Chronic intermittent ethanol exposure in early adolescent and adult male rats: effects on tolerance, social behavior, and ethanol intake.

    PubMed

    Broadwater, Margaret; Varlinskaya, Elena I; Spear, Linda P

    2011-08-01

    Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults. Adolescents drank significantly more ethanol than adults on a gram per kilogram basis, with intake uninfluenced by prior ethanol exposure at both ages. Adolescents and adults may differ in their ability and/or propensity to adapt to chronic ethanol exposure, with adults, but not adolescents, developing chronic metabolic tolerance. However, this chronic exposure regimen was sufficient to disrupt baseline levels of social behavior at both ages. Taken together, these results suggest that, despite the age-related differences in tolerance development, adolescents are as susceptible as adults to consequences of chronic ethanol exposure, particularly in terms of disruptions in social behavior. Whether these effects would last into adulthood remains to be determined. Copyright © 2011 by the Research Society on Alcoholism.

  12. Effectiveness of chronic care models: opportunities for improving healthcare practice and health outcomes: a systematic review.

    PubMed

    Davy, Carol; Bleasel, Jonathan; Liu, Hueiming; Tchan, Maria; Ponniah, Sharon; Brown, Alex

    2015-05-10

    The increasing prevalence of chronic disease and even multiple chronic diseases faced by both developed and developing countries is of considerable concern. Many of the interventions to address this within primary healthcare settings are based on a chronic care model first developed by MacColl Institute for Healthcare Innovation at Group Health Cooperative. This systematic literature review aimed to identify and synthesise international evidence on the effectiveness of elements that have been included in a chronic care model for improving healthcare practices and health outcomes within primary healthcare settings. The review broadens the work of other similar reviews by focusing on effectiveness of healthcare practice as well as health outcomes associated with implementing a chronic care model. In addition, relevant case series and case studies were also included. Of the 77 papers which met the inclusion criteria, all but two reported improvements to healthcare practice or health outcomes for people living with chronic disease. While the most commonly used elements of a chronic care model were self-management support and delivery system design, there were considerable variations between studies regarding what combination of elements were included as well as the way in which chronic care model elements were implemented. This meant that it was impossible to clearly identify any optimal combination of chronic care model elements that led to the reported improvements. While the main argument for excluding papers reporting case studies and case series in systematic literature reviews is that they are not of sufficient quality or generalizability, we found that they provided a more detailed account of how various chronic care models were developed and implemented. In particular, these papers suggested that several factors including supporting reflective healthcare practice, sending clear messages about the importance of chronic disease care and ensuring that leaders support the implementation and sustainability of interventions may have been just as important as a chronic care model's elements in contributing to the improvements in healthcare practice or health outcomes for people living with chronic disease.

  13. Promoting normal development and self-efficacy in school-age children managing chronic conditions.

    PubMed

    Mickley, Kristyn L; Burkhart, Patricia V; Sigler, April N

    2013-06-01

    Chronic conditions can affect school-age children in more ways than just physically. Normal childhood maturation is critical at this age, yet daily management of chronic symptoms can be challenging. This article describes 4 common childhood chronic illnesses (asthma, seizure disorders, diabetes, and cystic fibrosis), and the impact these conditions have on the developing child. Self-efficacy, the belief that one can effectively perform necessary skills, is essential to self-management of chronic conditions and contributes in a positive way to the child's normal development. Implications for clinical practice and future research are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. The immunomodulating role of exercise in metabolic disease.

    PubMed

    Lancaster, Graeme I; Febbraio, Mark A

    2014-06-01

    A lack of physical activity is linked to the development of many chronic diseases. It is now well established that the immune system and inflammation play a central role in the development of numerous chronic metabolic diseases including insulin resistance, type 2 diabetes, atherosclerosis, nonalcoholic fatty liver disease, and specific types of cancer. Physical exercise elicits potent anti-inflammatory effects that are likely to account for many of the salutary actions of regular exercise on chronic metabolic diseases. Here we review the anti-inflammatory and immunomodulatory mechanisms by which the beneficial effects of exercise on chronic metabolic diseases may be mediated. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. The effects of chronic stress on the human brain: From neurotoxicity, to vulnerability, to opportunity.

    PubMed

    Lupien, Sonia J; Juster, Robert-Paul; Raymond, Catherine; Marin, Marie-France

    2018-04-01

    For the last five decades, science has managed to delineate the mechanisms by which stress hormones can impact on the human brain. Receptors for glucocorticoids are found in the hippocampus, amygdala and frontal cortex, three brain regions involved in memory processing and emotional regulation. Studies have shown that chronic exposure to stress is associated with reduced volume of the hippocampus and that chronic stress can modulate volumes of both the amygdala and frontal cortex, suggesting neurotoxic effects of stress hormones on the brain. Yet, other studies report that exposure to early adversity and/or familial/social stressors can increase vulnerability to stress in adulthood. Models have been recently developed to describe the roles that neurotoxic and vulnerability effects can have on the developing brain. These models suggest that developing early stress interventions could potentially counteract the effects of chronic stress on the brain and results going along with this hypothesis are summarized. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Growth and Growth hormone - Insulin Like Growth Factor -I (GH-IGF-I) Axis in Chronic Anemias.

    PubMed

    Soliman, Ashraf T; De Sanctis, Vincenzo; Yassin, Mohamed; Adel, Ashraf

    2017-04-28

    Anaemia is a global public health problem affecting both developing and developed countries with major consequences for human health as well as social and economic development. It occurs at all stages of the life cycle, but is more prevalent in pregnant women and young children. Iron deficiency anaemia (IDA) was considered to be among the most important contributing factors to the global burden of disease. Prolonged and/or chronic anemia has a negative effect on linear growth especially during the rapid phases (infancy and puberty). Additionally infants with chronic IDA have delayed cognitive, motor, and affective development that may be long-lasting. In view of the significant impact of chronic anemias on growth, pediatricians endocrinologists and hematologists should advocate primary prevention and screening for growth disturbance in these forms of anemias. The extent of the negative effect of different forms of chronic anemias on linear growth and its possible reversibilty is addressed in this review. The possible mechanisms that may impair growth in the different forms of anemias are addressed with special attention to their effect on the growth hormone (GH) - insulin like growth factor -I (IGF-I).

  17. Neurobiological and neurocognitive effects of chronic cigarette smoking and alcoholism.

    PubMed

    Durazzo, Timothy C; Meyerhoff, Dieter J

    2007-05-01

    Chronic cigarette smoking is associated with adverse effects on cardiac, pulmonary, and vascular function as well as the increased risk for various forms of cancer. However, little is known about the effects of chronic smoking on human brain function. Although smoking rates have decreased in the developed world, they remain high in individuals with alcohol use disorders (AUD) and other neuropsychiatric conditions. Despite the high prevalence of chronic smoking in AUD, few studies have addressed the potential neurobiological or neurocognitive consequences of chronic smoking in alcohol use disorders. Here, we review the the neurobiological and neurocognitive findings in both AUD and chronic cigarette smoking, followed by a review of the effects of comorbid cigarette smoking on neurobiology and neurocognition in AUD. Recent research suggests that comorbid chronic cigarette smoking modulates magnetic resonance-detectable brain injury and neurocognition in alcohol use disorders and adversely affects neurobiological and neurocognitive recovery in abstinent alcoholics.. Consideration of the potential separate and interactive effects of chronic smoking and alcohol use disorders may have significant implications for pharmacological and behavioral treatment interventions.

  18. Developing effective chronic disease interventions in Africa: insights from Ghana and Cameroon

    PubMed Central

    2010-01-01

    Background Africa faces an urgent but 'neglected epidemic' of chronic disease. In some countries stroke, hypertension, diabetes and cancers cause a greater number of adult medical admissions and deaths compared to communicable diseases such as HIV/AIDS or tuberculosis. Experts propose a three-pronged solution consisting of epidemiological surveillance, primary prevention and secondary prevention. In addition, interventions must be implemented through 'multifaceted multi-institutional' strategies that make efficient use of limited economic and human resources. Epidemiological surveillance has been prioritised over primary and secondary prevention. We discuss the challenge of developing effective primary and secondary prevention to tackle Africa's chronic disease epidemic through in-depth case studies of Ghanaian and Cameroonian responses. Methods A review of chronic disease research, interventions and policy in Ghana and Cameroon instructed by an applied psychology conceptual framework. Data included published research and grey literature, health policy initiatives and reports, and available information on lay community responses to chronic diseases. Results There are fundamental differences between Ghana and Cameroon in terms of 'multi-institutional and multi-faceted responses' to chronic diseases. Ghana does not have a chronic disease policy but has a national health insurance policy that covers drug treatment of some chronic diseases, a culture of patient advocacy for a broad range of chronic conditions and mass media involvement in chronic disease education. Cameroon has a policy on diabetes and hypertension, has established diabetes clinics across the country and provided training to health workers to improve treatment and education, but lacks community and media engagement. In both countries churches provide public education on major chronic diseases. Neither country has conducted systematic evaluation of the impact of interventions on health outcomes and cost-effectiveness. Conclusions Both Ghana and Cameroon require a comprehensive and integrative approach to chronic disease intervention that combines structural, community and individual strategies. We outline research and practice gaps and best practice models within and outside Africa that can instruct the development of future interventions. PMID:20403170

  19. TElehealth in CHronic disease: mixed-methods study to develop the TECH conceptual model for intervention design and evaluation.

    PubMed

    Salisbury, Chris; Thomas, Clare; O'Cathain, Alicia; Rogers, Anne; Pope, Catherine; Yardley, Lucy; Hollinghurst, Sandra; Fahey, Tom; Lewis, Glyn; Large, Shirley; Edwards, Louisa; Rowsell, Alison; Segar, Julia; Brownsell, Simon; Montgomery, Alan A

    2015-02-06

    To develop a conceptual model for effective use of telehealth in the management of chronic health conditions, and to use this to develop and evaluate an intervention for people with two exemplar conditions: raised cardiovascular disease risk and depression. The model was based on several strands of evidence: a metareview and realist synthesis of quantitative and qualitative evidence on telehealth for chronic conditions; a qualitative study of patients' and health professionals' experience of telehealth; a quantitative survey of patients' interest in using telehealth; and review of existing models of chronic condition management and evidence-based treatment guidelines. Based on these evidence strands, a model was developed and then refined at a stakeholder workshop. Then a telehealth intervention ('Healthlines') was designed by incorporating strategies to address each of the model components. The model also provided a framework for evaluation of this intervention within parallel randomised controlled trials in the two exemplar conditions, and the accompanying process evaluations and economic evaluations. Primary care. The TElehealth in CHronic Disease (TECH) model proposes that attention to four components will offer interventions the best chance of success: (1) engagement of patients and health professionals, (2) effective chronic disease management (including subcomponents of self-management, optimisation of treatment, care coordination), (3) partnership between providers and (4) patient, social and health system context. Key intended outcomes are improved health, access to care, patient experience and cost-effective care. A conceptual model has been developed based on multiple sources of evidence which articulates how telehealth may best provide benefits for patients with chronic health conditions. It can be used to structure the design and evaluation of telehealth programmes which aim to be acceptable to patients and providers, and cost-effective. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice

    PubMed Central

    Poole, Rachel L.; Braak, David; Gould, Thomas J.

    2015-01-01

    Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, this suggests that the developing hippocampus may be sensitive to the effects of caffeine. PMID:25827925

  1. Transforming Pain Medicine: Adapting to Science and Society

    PubMed Central

    Borsook, David; Kalso, Eija

    2013-01-01

    The field of chronic pain medicine is currently facing enormous challenges. The incidence of chronic pain is increasing worldwide, particularly in the developed world. As a result, chronic pain is imposing a growing burden on Western societies in terms of cost of medical care and lost productivity. This burden is exacerbated by the fact that despite research efforts and a huge expenditure on treatment for chronic pain, clinicians have no highly effective treatments or definitive diagnostic measures for patients. The lack of an objective measure for pain impedes basic research into the biological and psychological mechanisms of chronic pain and clinical research into treatment efficacy. The development of objective measurements of pain and ability to predict treatment responses in the individual patient is critical to improving pain management. Finally, pain medicine must embrace the development of a new evidence-based therapeutic model that recognizes the highly individual nature of responsiveness to pain treatments, integrates bio-psycho-behavioral approaches, and requires proof of clinical effectiveness for the various treatments we offer our patients. In the long-term these approaches will contribute to providing better diagnoses and more effective treatments to lessen the current challenges in pain medicine. PMID:23468059

  2. The development and implementation of the Chronic Care Management Programme in Counties Manukau.

    PubMed

    Wellingham, John; Tracey, Jocelyn; Rea, Harold; Gribben, Barry

    2003-02-21

    To develop an effective and efficient process for the seamless delivery of care for targeted patients with specific chronic diseases. To reduce inexplicable variation and maximise use of available resources by implementing evidence-based care processes. To develop a programme that is acceptable and applicable to the Counties Manukau region. A model for the management of people with chronic diseases was developed. Model components and potential interventions were piloted. For each disease project, a return on investment was calculated and external evaluation was undertaken. The initial model was subsequently modified and individual disease projects aligned to it. The final Chronic Care Management model, agreed in September 2001, described a single common process. Key components were the targeting of high risk patients, organisation of cost effective interventions into a system of care, and an integrated care server acting as a data warehouse with a rules engine, providing flags and reminders. Return on investment analysis suggested potential savings for each disease component from $277 to $980 per person per annum. For selected chronic diseases, introduction of an integrated chronic care management programme, based on internationally accepted best practice processes and interventions can make significant savings, reducing morbidity and improving the efficiency of health delivery in the Counties Manukau region.

  3. Analysis of Why the Renal Dialysis Unit is Losing Money

    DTIC Science & Technology

    1997-06-30

    urinary obstruction, severe hypertension, diabetes mellitus, gout, and polycystic kidney disease. Patients with advanced chronic renal failure develop...failure. An excess amount of potassium in the body, also termed hyperkalemia , occurs in chronic renal failure because of inadequate renal excretion...Patients with hyperkalemia can develop skeletal muscle paralysis, but the most dangerous effect of hyperkalemia is the effect it has on the heart

  4. Integrated health system for chronic disease management: lessons learned from France.

    PubMed

    Stuart, Mary; Weinrich, Michael

    2004-02-01

    Rated number one in overall health system performance by the World Health Organization, the French spend less than half the amount on annual health care per capita that the United States spends. One contributing factor may be the attention given to chronic care. Since the mid-1900s, the French have developed regional community-based specialty systems for patients with chronic respiratory insufficiency or failure. COPD is the major cause of respiratory failure, the fourth leading cause of death in the United States, and its prevalence is increasing. Despite the clinical success of home mechanical ventilation and the potential for cost savings, providing such services in the United States remains a challenge. Lessons from France can inform the development of cost-effective chronic care models in the United States In this article, we review the French experience in the context of the United States Supreme Court's Olmstead decision, mandating that people in "more restrictive settings" such as nursing homes be offered community-based supports. We suggest that regional demonstration projects for patients with chronic respiratory failure or insufficiency can provide an important step in the development of effective chronic care systems in the United States

  5. The Australian Prevention Partnership Centre: systems thinking to prevent lifestyle-related chronic illness.

    PubMed

    Wilson, Andrew; Wutzke, Sonia; Overs, Marge

    2014-11-28

    Chronic diseases are the major cause of death in Australia and the biggest contributor to premature death and disability. Although prevention of chronic disease can be effective and cost-effective, it has proven difficult to systematically implement interventions that target important lifestyle-related risk factors for chronic disease such as poor nutrition, physical inactivity and harmful alcohol use. Prevention efforts targeting these lifestyle-related risk factors have had mixed success due to issues around designing and implementing effective interventions that address the complexity of risk factors, and incorporating evidence and implementing interventions at a scale, duration, intensity and quality required to achieve population effects. There is increasing recognition that multilevel, multisector approaches are required for the effective and sustained prevention of complex chronic disease. The Australian Prevention Partnership Centre, one of two National Health and Medical Research Council Partnership Centres established in 2013, is researching and developing systems perspectives to prevent lifestyle-related chronic disease in Australia. The Centre's collaborative approach is providing opportunities for researchers to work with policy makers and practitioners to develop research questions, conduct research, and analyse, interpret and disseminate the findings. As such, it is the model of interaction that is being tested as much as the specific projects. With its funding partners, the Centre has developed plans for more than 30 projects. It has also established four capacity units that will improve the gathering, sharing and use of evidence to build a prevention system in Australia. The Centre is exploring new ways to advance prevention by bringing together researchers, policy makers and practitioners to determine the information and actions needed for an effective prevention system for Australia.

  6. An overview of the management of patients with chronic pancreatitis.

    PubMed

    Johnstone, Carolyn C

    2016-11-23

    Chronic pancreatitis is a complex inflammatory condition characterised by irreversible damage to the pancreas. This article explores the pathophysiology of this condition and its effects on pancreatic function. It outlines the causes and presenting features of chronic pancreatitis, as well as its effect on patients' quality of life and the changes to their lifestyle that are likely to be required. Chronic pancreatitis cannot be cured; therefore, treatment aims to control pain, manage problems associated with malabsorption, and assess and manage long-term complications that may develop, such as insulin dependence.

  7. Effect of acute and chronic administration of caffeine on pain-like behaviors in rats with partial sciatic nerve injury.

    PubMed

    Wu, Wei-Ping; Hao, Jing-Xia; Fredholm, Bertil B; Wiesenfeld-Hallin, Zsuzsanna; Xu, Xiao-Jun

    2006-07-10

    Caffeine, used in many pain medications as an adjuvant analgesic, is an adenosine A1 and A2A receptor antagonist. Here we examined the effects of acute or chronic caffeine administration in rats after partial sciatic nerve injury. The hindpaw response to mechanical or cold stimulation was assessed following photochemically induced sciatic nerve injury which leads to hypersensitivity to these stimuli. Caffeine was administered i.p. acutely or in the drinking water chronically. The mechanical and cold hypersensitivity of sciatic nerve-injured rats was dose-dependently alleviated by acute systemic administration of caffeine (10-80 mg/kg). The effect of caffeine was, however, associated with side effects including locomotor stimulation or depression. Chronic oral administration (average daily doses 27.5 mg/kg/day or 61.5 mg/kg/day for 2 weeks) of caffeine starting at the time of nerve injury did not significantly affect the development of pain-like behaviors. Thus, acute, but not long term, caffeine intake reduced neuropathic pain state in nerve-injured rats, but only at very high doses. The potential hyperalgesic effect of chronic A1 adenosine receptor blockade may have been compensated for by an antinociceptive effect of caffeine through antagonism of A2A receptors and tolerance development.

  8. Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

    PubMed Central

    Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

    2014-01-01

    The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

  9. Etiologic factors of chronic constipation: review of the scientific evidence.

    PubMed

    Leung, Felix W

    2007-02-01

    Geriatric patient educational material and a general practice review suggest insufficient dietary fiber intake, inadequate fluid intake, decrease physical activity, side effects of drugs, hypothyroidism, sex hormones and colorectal cancer obstruction may play a role in the pathogenesis of constipation. A search of recent literature, however, reveals that there is a paucity of evidence-based publications that address the etiologic factors of chronic constipation. Much of current writings on the subject may be based primarily on myths handed down from one generation to the next. In the absence of well-designed studies, there do not appear to be sufficient evidence-based information to implicate the above as major etiologic factors in the development of chronic constipation. The etiological role of each of these factors in the development of chronic constipation deserves to be assessed by modern techniques and methodologies. Funding agencies including the government and industry sponsors should support the development of evidence-based data sets. The understanding of the etiology of chronic constipation is the foundation on which cost-effective management strategies are to be built.

  10. Vaccine Candidates against Nontypeable Haemophilus influenzae: a Review

    PubMed Central

    Behrouzi, Ava; Vaziri, Farzam; Rahimi-Jamnani, Fatemeh; Afrough, Parviz; Rahbar, Mohammad; Satarian, Fereshteh; Siadat, Seyed Davar

    2017-01-01

    Nonencapsulated, nontypeable Hemophilus influenzae (NTHi) remains an important cause of acute otitis and respiratory diseases in children and adults. NTHi bacteria are one of the major causes of respiratory tract infections, including acute otitis media, cystic fibrosis, and community-acquired pneumonia among children, especially in developing countries. The bacteria can also cause chronic diseases such as chronic bronchitis and chronic obstructive pulmonary disease in the lower respiratory tract of adults. Such bacteria express several outer membrane proteins, some of which have been studied as candidates for vaccine development. Due to the lack of effective vaccines as well as the spread and prevalence of NTHi worldwide, there is an urgent need to design and develop effective vaccine candidates against these strains. PMID:28088130

  11. Correlation of Noncancer Benchmark Doses in Short- and Long-Term Rodent Bioassays.

    PubMed

    Kratchman, Jessica; Wang, Bing; Fox, John; Gray, George

    2018-05-01

    This study investigated whether, in the absence of chronic noncancer toxicity data, short-term noncancer toxicity data can be used to predict chronic toxicity effect levels by focusing on the dose-response relationship instead of a critical effect. Data from National Toxicology Program (NTP) technical reports have been extracted and modeled using the Environmental Protection Agency's Benchmark Dose Software. Best-fit, minimum benchmark dose (BMD), and benchmark dose lower limits (BMDLs) have been modeled for all NTP pathologist identified significant nonneoplastic lesions, final mean body weight, and mean organ weight of 41 chemicals tested by NTP between 2000 and 2012. Models were then developed at the chemical level using orthogonal regression techniques to predict chronic (two years) noncancer health effect levels using the results of the short-term (three months) toxicity data. The findings indicate that short-term animal studies may reasonably provide a quantitative estimate of a chronic BMD or BMDL. This can allow for faster development of human health toxicity values for risk assessment for chemicals that lack chronic toxicity data. © 2017 Society for Risk Analysis.

  12. Food restriction affects Y-maze spatial recognition memory in developing mice.

    PubMed

    Fu, Yu; Chen, Yanmei; Li, Liane; Wang, Yumei; Kong, Xiangyang; Wang, Jianhong

    2017-08-01

    The ambiguous effects of food restriction (FR) on cognition in rodents have been mostly explored in the aged brain by a variety of paradigms, in which either rewards or punishments are involved. This study aims to examine the effects of chronic and acute FR with varying intensities on spatial recognition memory in developing mice. We have used a Y-maze task that is based on the innate tendency of rodents to explore novel environments. In chronic FR, mice had 70-30% chow of control for seven weeks. In acute FR, mice were food restricted for 12-48h before the tests. We found that chronic FR had no effect on the preference of mice for novelty in the Y-maze, but severe FR (50-30% of control) caused impairment on spatial recognition memory. The impairment significantly correlated with the slow weight growth induced by FR. Acute FR also did not affect the novelty preference of mice, but either improved or impaired the memory retention. These data suggest chronic FR impairs Y-maze spatial recognition memory in developing mice depending on FR intensity and individual tolerability of the FR. Moreover, acute FR exerts diverse effects on the memory, either positive or negative. Our findings have revealed new insights on the effects of FR on spatial recognition memory in developing animals. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  13. 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.

  14. Chronic Pain, Chronic Opioid Addiction: a Complex Nexus.

    PubMed

    Salsitz, Edwin A

    2016-03-01

    Over the past two decades, there has been a significant increase in the prescribing of opioids, with associated increases in opioid addiction and overdose deaths. This article reviews the evidence for the effectiveness and risk of developing an opioid use disorder (OUD) in those patients treated with chronic opioid therapy (COT) for chronic non-cancer pain (CNCP). Rates of development of OUD range from 0-50 %, and aberrant drug related behaviors (ADRBs) are reported to be 20 %. Health care providers must properly assess, screen, and carefully monitor patients on COT utilizing evidence-based tools.

  15. Effects of stress on alcohol drinking: a review of animal studies

    PubMed Central

    Lopez, Marcelo F.; Doremus-Fitzwater, Tamara L.

    2011-01-01

    Rationale While stress is often proposed to play a significant role in influencing alcohol consumption, the relationship between stress and alcohol is complex and poorly understood. Over several decades, stress effects on alcohol drinking have been studied using a variety of animal models and experimental procedures, yet this large body of literature has generally produced equivocal results. Objectives This paper reviews results from animal studies in which alcohol consumption is evaluated under conditions of acute/sub-chronic stress exposure or models of chronic stress exposure. Evidence also is presented indicating that chronic intermittent alcohol exposure serves as a stressor that consequently influences drinking. Results The effects of various acute/sub-chronic stress procedures on alcohol consumption have generally been mixed, but most study outcomes suggest either no effect or decreased alcohol consumption. In contrast, most studies indicate that chronic stress, especially when administered early in development, results in elevated drinking later in adulthood. Chronic alcohol exposure constitutes a potent stressor itself, and models of chronic intermittent alcohol exposure reliably produce escalation of voluntary alcohol consumption. Conclusions A complex and dynamic interplay among a wide array of genetic, biological, and environmental factors govern stress responses, regulation of alcohol drinking, and the circumstances in which stress modulates alcohol consumption. Suggestions for future directions and new approaches are presented that may aid in developing more sensitive and valid animal models that not only better mimic the clinical situation, but also provide greater understanding of mechanisms that underlie the complexity of stress effects on alcohol drinking. PMID:21850445

  16. A meta-analysis of education effects on chronic disease: the causal dynamics of the Population Education Transition Curve.

    PubMed

    Smith, William C; Anderson, Emily; Salinas, Daniel; Horvatek, Renata; Baker, David P

    2015-02-01

    As the Epidemiological Transition progresses worldwide, chronic diseases account for the majority of deaths in developed countries and a rising proportion in developing countries indicating a new global pattern of mortality and health challenges into the future. Attainment of formal education is widely reported to have a negative gradient with risk factors and onset of chronic disease, yet there has not been a formal assessment of this research. A random-effects meta-analysis finds that across 414 published effects more education significantly reduces the likelihood of chronic disease, except for neoplastic diseases with substantial genetic causes. Some studies, however, report null effects and other research on infectious disease report positive education gradients. Instead of assuming these contradictory results are spurious, it is suggested that they are part of a predictable systemic interaction between multiple mediating effects of education and the Epidemiological Transition stage of the population; and thus represent one case of the Population Education Transition Curve modeling changes in the association between education and health as dependent on population context. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Computer Assisted Chronic Disease Management: Does It Work? A Pilot Study Using Mixed Methods

    PubMed Central

    Jones, Kay M.; Biezen, Ruby; Piterman, Leon

    2013-01-01

    Background. Key factors for the effective chronic disease management (CDM) include the availability of practical and effective computer tools and continuing professional development/education. This study tested the effectiveness of a computer assisted chronic disease management tool, a broadband-based service known as cdmNet in increasing the development of care plans for patients with chronic disease in general practice. Methodology. Mixed methods are the breakthrough series methodology (workshops and plan-do-study-act cycles) and semistructured interviews. Results. Throughout the intervention period a pattern emerged suggesting GPs use of cdmNet initially increased, then plateaued practice nurses' and practice managers' roles expanded as they became more involved in using cdmNet. Seven main messages emerged from the GP interviews. Discussion. The overall use of cdmNet by participating GPs varied from “no change” to “significant change and developing many the GPMPs (general practice management plans) using cdmNet.” The variation may be due to several factors, not the least, allowing GPs adequate time to familiarise themselves with the software and recognising the benefit of the team approach. Conclusion. The breakthrough series methodology facilitated upskilling GPs' management of patients diagnosed with a chronic disease and learning how to use the broadband-based service cdmNet. PMID:24959576

  18. Early History of Chronic Obstructive Pulmonary Disease 1808-1980.

    PubMed

    Watson, R Ann; Pride, Neil B

    2016-01-01

    COPD has become a more popular research area in the last 3 decades, yet the first clear descriptions of acute and chronic bronchitis were in 1808. This brief history, comprehensively referenced, leads us through the early developments in respiratory physiology and their applications. It emphasises the early history of chronic bronchitis and emphysema in the 19(th) and early 20(th) centuries, long before the dominant effects of cigarette smoking emerged. This remains relevant to developing countries today.

  19. Chronic Treatment With Aripiprazole Prevents Development of Dopamine Supersensitivity and Potentially Supersensitivity Psychosis

    PubMed Central

    Tadokoro, Shigenori; Okamura, Naoe; Sekine, Yoshimoto; Kanahara, Nobuhisa; Hashimoto, Kenji; Iyo, Masaomi

    2012-01-01

    Background: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D2 dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. Methods: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D2 receptor density (N = 4-10/condition/experiment). Results: Chronic treatment with HAL led to significant increases in locomotor response and D2 receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D2 density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D2 density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D2 density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. Conclusions: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia. PMID:21402722

  20. IGEA--a chronic disease management project for people with diabetes.

    PubMed

    Maggini, Marina

    2009-01-01

    Chronic diseases can be prevented and controlled using available knowledge. Moreover, the solutions are not only effective but can be highly cost-effective. Chronic care model and disease management have emerged, in the last decades, as new models of care delivery. The two models share the objective of improving the quality of care for people with chronic diseases while optimizing health care expenditure. In Italy, within the National Prevention Plan, the Italian Centre for Disease Prevention and Control of the Ministry of Health, and the Istituto Superiore di Sanità (ISS) are developing the IGEA project, which defines a comprehensive strategy for implementing a chronic disease management intervention for people with diabetes.

  1. Population causes and consequences of leading chronic diseases: a comparative analysis of prevailing explanations.

    PubMed

    Stuckler, David

    2008-06-01

    The mortality numbers and rates of chronic disease are rising faster in developing than in developed countries. This article compares prevailing explanations of population chronic disease trends with theoretical and empirical models of population chronic disease epidemiology and assesses some economic consequences of the growth of chronic diseases in developing countries based on the experiences of developed countries. Four decades of male mortality rates of cardiovascular and chronic noncommunicable diseases were regressed on changes in and levels of country income per capita, market integration, foreign direct investment, urbanization rates, and population aging in fifty-six countries for which comparative data were available. Neoclassical economic growth models were used to estimate the effect of the mortality rates of chronic noncommunicable diseases on economic growth in high-income OECD countries. Processes of economic growth, market integration, foreign direct investment, and urbanization were significant determinants of long-term changes in mortality rates of heart disease and chronic noncommunicable disease, and the observed relationships with these social and economic factors were roughly three times stronger than the relationships with the population's aging. In low-income countries, higher levels of country income per capita, population urbanization, foreign direct investment, and market integration were associated with greater mortality rates of heart disease and chronic noncommunicable disease, less increased or sometimes reduced rates in middle-income countries, and decreased rates in high-income countries. Each 10 percent increase in the working-age mortality rates of chronic noncommunicable disease decreased economic growth rates by close to a half percent. Macrosocial and macroeconomic forces are major determinants of population rises in chronic disease mortality, and some prevailing demographic explanations, such as population aging, are incomplete on methodological, empirical, and policy grounds. Rising chronic disease mortality rates will significantly reduce economic growth in developing countries and further widen the health and economic gap between the developed and developing world.

  2. Population Causes and Consequences of Leading Chronic Diseases: A Comparative Analysis of Prevailing Explanations

    PubMed Central

    Stuckler, David

    2008-01-01

    Context The mortality numbers and rates of chronic disease are rising faster in developing than in developed countries. This article compares prevailing explanations of population chronic disease trends with theoretical and empirical models of population chronic disease epidemiology and assesses some economic consequences of the growth of chronic diseases in developing countries based on the experiences of developed countries. Methods Four decades of male mortality rates of cardiovascular and chronic noncommunicable diseases were regressed on changes in and levels of country income per capita, market integration, foreign direct investment, urbanization rates, and population aging in fifty-six countries for which comparative data were available. Neoclassical economic growth models were used to estimate the effect of the mortality rates of chronic noncommunicable diseases on economic growth in high-income OECD countries. Findings Processes of economic growth, market integration, foreign direct investment, and urbanization were significant determinants of long-term changes in mortality rates of heart disease and chronic noncommunicable disease, and the observed relationships with these social and economic factors were roughly three times stronger than the relationships with the population's aging. In low-income countries, higher levels of country income per capita, population urbanization, foreign direct investment, and market integration were associated with greater mortality rates of heart disease and chronic noncommunicable disease, less increased or sometimes reduced rates in middle-income countries, and decreased rates in high-income countries. Each 10 percent increase in the working-age mortality rates of chronic noncommunicable disease decreased economic growth rates by close to a half percent. Conclusions Macrosocial and macroeconomic forces are major determinants of population rises in chronic disease mortality, and some prevailing demographic explanations, such as population aging, are incomplete on methodological, empirical, and policy grounds. Rising chronic disease mortality rates will significantly reduce economic growth in developing countries and further widen the health and economic gap between the developed and developing world. PMID:18522614

  3. [Adaptation strategies faced with chronic pain].

    PubMed

    Bioy, Antoine

    2017-05-01

    Chronic pain constitutes a challenge for patients. It makes them uneasy with regard to their personality, their corporality and their life balance, and leaves long-lasting effects on their experience as a patient. The development of adaptation strategies and resources to deal with chronic pain is therefore essential. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

    PubMed Central

    Chou, Roger; Fanciullo, Gilbert J.; Fine, Perry G.; Adler, Jeremy A.; Ballantyne, Jane C.; Davies, Pamela; Donovan, Marilee I.; Fishbain, David A.; Foley, Kathy M.; Fudin, Jeffrey; Gilson, Aaron M.; Kelter, Alexander; Mauskop, Alexander; O'Connor, Patrick G.; Passik, Steven D.; Pasternak, Gavril W.; Portenoy, Russell K.; Rich, Ben A.; Roberts, Richard G.; Todd, Knox H.; Miaskowski, Christine

    2014-01-01

    Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices. Perspective: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel following a systematic review of the evidence. PMID:19187889

  5. Adolescent rats are resistant to the development of ethanol-induced chronic tolerance and ethanol-induced conditioned aversion.

    PubMed

    Pautassi, Ricardo Marcos; Godoy, Juan Carlos; Molina, Juan Carlos

    2015-11-01

    The analysis of chronic tolerance to ethanol in adult and adolescent rats has yielded mixed results. Tolerance to some effects of ethanol has been reported in adolescents, yet other studies found adults to exhibit greater tolerance than adolescents or comparable expression of the phenomena at both ages. Another unanswered question is how chronic ethanol exposure affects subsequent ethanol-mediated motivational learning at these ages. The present study examined the development of chronic tolerance to ethanol's hypothermic and motor stimulating effects, and subsequent acquisition of ethanol-mediated odor conditioning, in adolescent and adult male Wistar rats given every-other-day intragastric administrations of ethanol. Adolescent and adult rats exhibited lack of tolerance to the hypothermic effects of ethanol during an induction phase; whereas adults, but not adolescents, exhibited a trend towards a reduction in hypothermia at a challenge phase (Experiment 1). Adolescents, unlike adults, exhibited ethanol-induced motor activation after the first ethanol administration. Adults, but not adolescents, exhibited conditioned odor aversion by ethanol. Subsequent experiments conducted only in adolescents (Experiment 2, Experiment 3 and Experiment 4) manipulated the context, length and predictability of ethanol administration. These manipulations did not promote the expression of ethanol-induced tolerance. This study indicated that, when moderate ethanol doses are given every-other day for a relatively short period, adolescents are less likely than adults to develop chronic tolerance to ethanol-induced hypothermia. This resistance to tolerance development could limit long-term maintenance of ethanol intake. Adolescents, however, exhibited greater sensitivity than adults to the acute motor stimulating effects of ethanol and a blunted response to the aversive effects of ethanol. This pattern of response may put adolescents at risk for early initiation of ethanol intake. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. New and emerging therapies for acute and chronic graft versus host disease

    PubMed Central

    Hill, LaQuisa; Alousi, Amin; Kebriaei, Partow; Mehta, Rohtesh; Rezvani, Katayoun; Shpall, Elizabeth

    2017-01-01

    Graft versus host disease (GVHD) remains a major cause of morbidity and mortality following allogeneic hematopoietic stem-cell transplantation (HSCT). Despite the use of prophylactic GVHD regimens, a significant proportion of transplant recipients will develop acute or chronic GVHD following HSCT. Corticosteroids are standard first-line therapy, but are only effective in roughly half of all cases with ~50% of patients going on to develop steroid-refractory disease, which increases the risk of nonrelapse mortality. While progress has been made with improvements in survival outcomes over time, corticosteroids are associated with significant toxicities, and many currently available salvage therapies are associated with increased immunosuppression, infectious complications, and potential loss of the graft versus leukemia (GVL) effect. Thus, there is an unmet need for development of newer treatment strategies for both acute and chronic GVHD to improve long-term post-transplant outcomes and quality of life for HSCT recipients. Here, we provide a concise review of major emerging therapies currently being studied in the treatment of acute and chronic GVHD. PMID:29317998

  7. Effect of environment on the long-term consequences of chronic pain

    PubMed Central

    Bushnell, MC; Case, LK; Ceko, M; Cotton, VA; Gracely, JL; Low, LA; Pitcher, MH; Villemure, C

    2014-01-01

    Much evidence from pain patients and animal models shows that chronic pain does not exist in a vacuum, but has varied co-morbidities and far-reaching consequences. Patients with long-term pain often develop anxiety and depression and can manifest changes in cognitive functioning, particularly with working memory. Longitudinal studies in rodent models also show the development of anxiety-like behavior and cognitive changes weeks to months after an injury causing long-term pain. Brain imaging studies in pain patients and rodent models find that chronic pain is associated with anatomical and functional alterations in the brain. Nevertheless, studies in humans reveal that life-style choices, such as the practice of meditation or yoga, can reduce pain perception and have the opposite effect on the brain as does chronic pain. In rodent models, studies show that physical activity and a socially enriched environment reduce pain behavior and normalize brain function. Together, these studies suggest that the burden of chronic pain can be reduced by non-pharmacological interventions. PMID:25789436

  8. Chronic stress from adolescence to aging in the prefrontal cortex: A neuroimmune perspective.

    PubMed

    Macht, Victoria A; Reagan, Lawrence P

    2018-04-01

    The development of the organism is a critical variable which influences the magnitude, duration, and reversibility of the effects of chronic stress. Such factors are relevant to the prefrontal cortex (PFC), as this brain region is the last to mature, the first to decline, and is highly stress-sensitive. Therefore, this review will examine the intersection between the nervous system and immune system at glutamatergic synapses in the PFC across three developmental periods: adolescence, adulthood, and aging. Glutamatergic synapses are tightly juxtaposed with microglia and astrocytes, and each of these cell types exhibits their own developmental trajectory. Not only does chronic stress differentially impact each of these cell types across development, but chronic stress also alters intercellular communication within this quad-partite synapse. These observations suggest that developmental shifts in both neural and immune function across neurons, microglia, and astrocytes mediate shifting effects of chronic stress on glutamatergic transmission. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. The global impact of noncommunicable diseases: estimates and projections.

    PubMed

    Manton, K G

    1988-01-01

    With the aging of populations in developing countries there is both a demographic and an epidemiological transition which affects the impact of chronic degenerative diseases on the health status of the populations. Demographic transition takes place in countries where there are effective programmes of disease control which allow for survival during the early years of childhood and adolescence. This results in an increase in life expectancy which places larger proportions of the population in the age range (60 years and older) in which chronic degenerative diseases become the major determinants of health status. Epidemiological transition in diseases may also be brought about by shifts in social and economic patterns which favour detrimental changes in risk factors for the chronic degenerative diseases. Such changes may include health-related behaviour which augments dietary consumption of fats and alcohol, increases obesity, increases smoking and decreases physical activity. Such changes in risk-factor levels increase the prevalence of chronic degenerative diseases which manifest themselves at later ages, and for which early preventive actions could be cost-effective. In order to illustrate the impact of both demographic and risk-factor effects, analyses are made of the impact of increases in life expectancy on cause-specific mortality in both developing and developed countries. It is shown that there is great similarity in the effect of major noncommunicable diseases on the life expectancy of adults in both developed and developing countries. The major differences are seen to be in the proportions of deaths expected from such diseases as cancer, diabetes, heart disease, stroke and cirrhosis; but not in the distribution of age at death which is the better measure of disease impact. Demographic analyses, computing indirect estimates of mortality, also demonstrate that there are currently more chronic disease deaths in developing than developed countries and that as expectation of life increases in developing countries the global chronic disease burden will be greatly concentrated in the developing countries. Analyses of risk-factor reduction by feasible intervention strategies, e.g. smoking cessation campaigns, treatment of high blood pressure, using relationships between risk factors and diseases established in longitudinal studies carried out in developed countries, point out that the effect of risk-factor control in long-living populations can be hidden by the dependency of risk factors and various related causes of death, e.g. smoking has an impact on lung cancer, ischaemic heart disease and emphysema, but at different ages.(ABSTRACT TRUNCATED AT 400 WORDS)

  10. Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments

    PubMed Central

    Elhabazi, K; Trigo, JM; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, JJ; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

    2012-01-01

    BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. PMID:21718302

  11. Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments.

    PubMed

    Elhabazi, K; Trigo, J M; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, J J; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

    2012-01-01

    BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  12. Chronic Grief Management for Dementia Caregivers in Transition: Intervention Development and Implementation

    PubMed Central

    Paun, Olimpia; Farran, Carol J.

    2013-01-01

    Research reveals that Alzheimer’s disease (AD) caregivers (CGs) do not relinquish their role after placing a family member in long-term care. Caregivers report increased emotional upset around the time of placement, with sustained losses over time leading to chronic grief. Chronic grief increases caregivers’ risk for depression and suicide. There are no documented interventions designed to decrease CGs chronic grief post placement. The Chronic Grief Management Intervention (CGMI) builds on existing evidence to target caregiver chronic grief in the transition of a family member into long-term care. The intervention is structured into three major components: 1) knowledge, 2) skill in communication and conflict resolution, and 3) chronic grief mangement skill. The 12-week intervention was pilot tested with thirty four caregivers for feasibility and preliminary effects on caregiver skill, knowledge, chronic grief, and depression. This article presents a general study description while focusing on the development and implementation of the CGMI. PMID:22084962

  13. Physical and psychosocial factors in the prevention of chronic pain in older age.

    PubMed

    Fancourt, D; Steptoe, A

    2018-06-24

    Chronic pain is recognised as a major challenge as people age. Yet, despite growing research on chronic pain management, there is little research into chronic pain prevention. So there is a clear need to identify multimodal activities that could be encouraged amongst older adults as part of a healthy lifestyle to reduce the incidence risk of chronic pain. Using data from the English Longitudinal Study of Ageing we tracked 2,631 adults aged 50+ who were free from chronic pain at baseline across a decade and explore whether physical or psychosocial factors reduced the risk of developing chronic pain. In relation to physical factors, engaging in vigorous weekly activity was protective against the development of chronic pain (OR=0.74, SE=0.07, CI=0.62 to 0.89) when controlling for all identified socio-economic, health and social confounders. But no effects were found for moderate weekly activity. In relation to psychosocial factors, cultural engagement was also protective against the development of chronic pain (OR=0.75, SE=0.07, CI=0.63 to 0.91), but community group participation was not. These findings extend previous work showing that physical activity and psychosocial factors such as positive affect are key factors in the long-term success of chronic pain self-management. Future interventional studies for chronic pain are encouraged. Perspective This article explores whether physical and psychosocial activities could reduce the risk of developing chronic pain in older age. These results could potentially help clinicians to recommend multimodal activities as part of a broader healthy lifestyle for those aged 50+ to reduce the incidence rate of chronic pain. Copyright © 2018. Published by Elsevier Inc.

  14. [Effects of diazepam on mixed anxiety/depression state in male mice].

    PubMed

    Galiamina, A G; Smagin, D A; Kovalenko, I L; Bondar', N P; Kudriavtseva, N N

    2013-11-01

    Chronic social defeat stress in daily agonistic interactions leads to the development of mixed anxiety/depression state in male mice. This paper aimed to study the effects of chronic diazepam treatment on the psychoemotional state of these animals. Diazepam (0.5 mg/kg, i/p, Polfa Tarchomin S. A.) or saline was chronically injected into male mice for two weeks on the background of continuing agonistic interactions (preventive treatment) or into male mice with mixed anxiety/depression state after stopping of social confrontations (therapeutic treatment). Then, the animals were studied in the partition, plus-maze and Porsolt' tests, estimating the levels of communicativeness, anxiety and depressiveness, respectively. Preventive diazepam treatment had a weak protective anxiolytic and pro-depressive effect. The therapeutic diazepam treatment didn't influence on the anxiety and depression-like state. Chronic diazepam was ineffective for the treatment of the mixed anxiety/depression state in male mice. Different effects ofdiazepam on anxiety and depression-like states under preventive treatment confirmed our conclusion shown earlier about the independent development of these pathologies at least in our experimental paradigm.

  15. 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

  16. Psychometric qualities of questionnaires for the assessment of otitis media impact.

    PubMed

    Timmerman, A A; Meesters, C M G; Speyer, R; Anteunis, L J C

    2007-12-01

    The assessment of impact and evaluation of treatment effects in chronic otitis media (OM) calls for a much broader approach than just examining the presence of middle ear effusion or hearing loss. It is increasingly recognised that this condition may result in a comprised quality of life. Several studies have used proxy completed questionnaires to objectify the illness experience associated with chronic OM. To review questionnaires which have been developed to describe the effects of chronic OM on the daily functioning of children. Psychometric properties have been evaluated, in addition to discriminative and evaluative qualities. A systematic review of publications pertaining to developed questionnaires related with chronic OM. Systematic literature searches of PubMed (1966-January 2007) and EMBASE (1989-January 2007) were conducted, supplemented by using free text words to identify publications after January 2005. The included 15 questionnaires were developed for children with recurrent or persistent OM, describing functional health status (FHS), while two questionnaires also evaluate the effect of tympanostomy tubes insertion. The questionnaires generally cover six impact areas (physical symptoms, child development, educational performance, emotional/practical burden and general health status) with physical symptoms being the most prominant. The OM8-30, OMO-22 and OM-6 adequately reflect the multidimensional aspects of FHS in chronic OM. The OMO-22 and OM8-30 show the best psychometric properties for the discrimination of impact severity between children, while the OM-6 was found to have the best qualities for the evaluation of clinical change. Clinical applicability is crucial for the assessment of FHS in chronic OM, but requires a trade-off with necessary psychometric properties.

  17. Acid-Base Disorders in Patients with Chronic Obstructive Pulmonary Disease: A Pathophysiological Review

    PubMed Central

    Bruno, Cosimo Marcello; Valenti, Maria

    2012-01-01

    The authors describe the pathophysiological mechanisms leading to development of acidosis in patients with chronic obstructive pulmonary disease and its deleterious effects on outcome and mortality rate. Renal compensatory adjustments consequent to acidosis are also described in detail with emphasis on differences between acute and chronic respiratory acidosis. Mixed acid-base disturbances due to comorbidity and side effects of some drugs in these patients are also examined, and practical considerations for a correct diagnosis are provided. PMID:22500110

  18. Appendix E. Analysis of Chronic Toxicity Data and Acute Chronic Ratios (ACRs) in Support of Deriving Chronic HC5s: Acetylcholinesterase Inhibitors

    EPA Science Inventory

    The analysis described in this appendix is one of several conducted in support of developing a common methodology for assessing chemical effects on aquatic animals for use by the USEPA Office of Pesticide Programs (OPP) and the Office of Water (OW). Other appendices describe met...

  19. Back to Basics: The Effect of Healthy Diet and Exercise on Chronic Disease Management.

    PubMed

    Allison, Robert L

    2017-01-01

    The increase in obesity rates in the U.S. and other less developed industrial countries have led to a worldwide epidemic of chronic disease states. Increased obesity rates are implicated in the treatment failures for illnesses such as coronary artery disease, diabetes, heart failure, hypertension and cancer. Effective prevention of obesity through diet and exercise contributes to the successful medical management of multiple chronic disease states. Review the last 10 years of literature (2006-2016) on the effects of diet and exercise as they relate to the prevention of chronic disease. Cochran Database of Systematic Reviews and other original articles using the National Center for Biotechnical Information database. The success in management of chronic disease lies in a physician's ability to educate patients and effective utilization of the resources available to that provider. Patient accountability for their individual chronic disease states is a problem related to patient education, patient participation, access to care, and payment resources. Financial, racial, and socioeconomic barriers must be addressed in the creation of an effective plan. Teaching on the importance of diet and exercise needs to occur early in life and be continually reinforced for successful outcomes. In the last 10 years, there has not been a significant study suggesting a single successful model of diet and exercise that can control chronic diseases. Cardiac, diabetic, and cancer patients have reduced hospital admissions, improved diabetic control, and improved quality of life scores related to coordinated diet and exercise programs, however. Patients may be unwilling or unable to be accountable for health care coordination. The development of exercise and obesity prevention policies and the adjustment in financial rewards to health care organizations will have a major impact in implementing these programs over the next 10 years.

  20. Chronic stress and neural function: accounting for sex and age.

    PubMed

    Luine, V N; Beck, K D; Bowman, R E; Frankfurt, M; Maclusky, N J

    2007-10-01

    Cognitive responses to stress follow the temporally dependent pattern originally established by Selye (1) wherein short-term stressors elicit adaptive responses whereas continued stress (chronic) results in maladaptive changes--deleterious effects on physiological systems and impaired cognition. However, this pattern for cognitive effects appears to apply to only half the population (males) and, more specifically, to young, adult males. Females show different cognitive responses to stress. In contrast to impaired cognition in males after chronic stress, female rodents show enhanced performance on the same memory tasks after the same stress. Not only cognition, but anxiety, shows sex-dependent changes following chronic stress--stress is anxiolytic in males and anxiogenic in females. Moreover, behavioral responses to chronic stress are different in developing as well as aging subjects (both sexes) as compared to adults. In aged rats, chronic stress enhances recognition memory in both sexes, does not alter spatial memory, and anxiety effects are opposite to young adults. When pregnant dams are exposed to chronic stress, at adulthood the offspring display yet different consequences of stress on anxiety and cognition, and, in contrast to adulthood when the behavioral effects of stress are reversible, prenatal stress effects appear enduring. Changing levels of estradiol in the sexes over the lifespan appear to contribute to the differences in response to stress. Thus, theories of stress dependent modulations in CNS function--developed solely in male models, focused on peripheral physiological processes and tested in adults--may require revision when applied to a more diverse population (age- and sex-wise) at least in relation to the neural functions of cognition and anxiety. Moreover, these results suggest that other stressors and neural functions should be investigated to determine whether age, sex and gonadal hormones also have an impact.

  1. Development and Usability Evaluation of an Art and Narrative-Based Knowledge Translation Tool for Parents With a Child With Pediatric Chronic Pain: Multi-Method Study

    PubMed Central

    Reid, Kathy; Hartling, Lisa; Ali, Samina; Le, Anne; Norris, Allison

    2017-01-01

    Background Chronic pain in childhood is increasingly being recognized as a significant clinical problem for children and their families. Previous research has identified that families want information about the causes of their child’s chronic pain, treatment options, and effective strategies to help their child cope with the pain. Unfortunately, parents have reported that finding this information can be challenging. Objective The aim of this study was to actively work together with children attending a pediatric chronic pain clinic and their parents to develop, refine, and evaluate the usability of an art and narrative-based electronic book (e-book) for pediatric chronic pain. Methods A multiphase, multi-method research design employing patient engagement techniques was used to develop, refine, and evaluate the usability of an art and narrative based e-book for pediatric chronic pain management to facilitate knowledge translation for parents with a child with chronic pain. The multiple phases included the following: (1) qualitative interviews to compile parents’ narratives using qualitative interviews; (2) qualitative data analysis; (3) development of an e-book prototype; (4) expert clinician feedback; (5) parent usability evaluation, knowledge change, and confidence in knowledge responses using an electronic survey; (6) e-book refinement; and (7) dissemination of the e-book. Results A 48-page e-book was developed to characterize the experiences of a family living with a child with chronic pain. The e-book was a composite narrative of the parent interviews and encompassed descriptions of the effects the condition has on each member of the family. This was merged with the best available research evidence on the day-to-day management of pediatric chronic pain. The e-book was vetted for clinical accuracy by expert pediatric pain clinicians. All parents that participated in the usability evaluation (N=14) agreed or strongly agreed the content of the e-book was easy to understand and stated that they would recommend the e-book to other families who have children with chronic pain. Our research identified up to a 21.4% increase in knowledge after using the e-book, and paired t tests demonstrated a statistically significant difference in confidence in answering two of the five knowledge questions (chronic pain is a disease involving changes in the nervous system; the use of ibuprofen is usually effective at controlling chronic pain); t13=0.165, P=.001 and t13=0.336, P=.002, respectively, after being exposed to the e-book. Conclusions Our results demonstrate that parents positively rated an e-book developed for parents with a child with chronic pain. Our results also identify that overall, parents’ knowledge increased after using the e-book, and confidence in their knowledge about chronic pain and its management increased in two aspects after e-book exposure. These results suggest that art and narrative-based knowledge translation interventions may be useful in transferring complex health information to parents. PMID:29242180

  2. Development and Usability Evaluation of an Art and Narrative-Based Knowledge Translation Tool for Parents With a Child With Pediatric Chronic Pain: Multi-Method Study.

    PubMed

    Reid, Kathy; Hartling, Lisa; Ali, Samina; Le, Anne; Norris, Allison; Scott, Shannon D

    2017-12-14

    Chronic pain in childhood is increasingly being recognized as a significant clinical problem for children and their families. Previous research has identified that families want information about the causes of their child's chronic pain, treatment options, and effective strategies to help their child cope with the pain. Unfortunately, parents have reported that finding this information can be challenging. The aim of this study was to actively work together with children attending a pediatric chronic pain clinic and their parents to develop, refine, and evaluate the usability of an art and narrative-based electronic book (e-book) for pediatric chronic pain. A multiphase, multi-method research design employing patient engagement techniques was used to develop, refine, and evaluate the usability of an art and narrative based e-book for pediatric chronic pain management to facilitate knowledge translation for parents with a child with chronic pain. The multiple phases included the following: (1) qualitative interviews to compile parents' narratives using qualitative interviews; (2) qualitative data analysis; (3) development of an e-book prototype; (4) expert clinician feedback; (5) parent usability evaluation, knowledge change, and confidence in knowledge responses using an electronic survey; (6) e-book refinement; and (7) dissemination of the e-book. A 48-page e-book was developed to characterize the experiences of a family living with a child with chronic pain. The e-book was a composite narrative of the parent interviews and encompassed descriptions of the effects the condition has on each member of the family. This was merged with the best available research evidence on the day-to-day management of pediatric chronic pain. The e-book was vetted for clinical accuracy by expert pediatric pain clinicians. All parents that participated in the usability evaluation (N=14) agreed or strongly agreed the content of the e-book was easy to understand and stated that they would recommend the e-book to other families who have children with chronic pain. Our research identified up to a 21.4% increase in knowledge after using the e-book, and paired t tests demonstrated a statistically significant difference in confidence in answering two of the five knowledge questions (chronic pain is a disease involving changes in the nervous system; the use of ibuprofen is usually effective at controlling chronic pain); t 13 =0.165, P=.001 and t 13 =0.336, P=.002, respectively, after being exposed to the e-book. Our results demonstrate that parents positively rated an e-book developed for parents with a child with chronic pain. Our results also identify that overall, parents' knowledge increased after using the e-book, and confidence in their knowledge about chronic pain and its management increased in two aspects after e-book exposure. These results suggest that art and narrative-based knowledge translation interventions may be useful in transferring complex health information to parents. ©Kathy Reid, Lisa Hartling, Samina Ali, Anne Le, Allison Norris, Shannon D Scott. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.12.2017.

  3. Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Effect of Food Ration on Sediment Toxicity

    DTIC Science & Technology

    1993-09-01

    developing oocytes. In effect , gametogenesis and subsequent reproductive success are largely dependent on the energy and metabolic substrates assimi- lated...Miscellaneous Paper D-93-4 September 1993 US Army Corps AD-A269 901 of Engineers Waterways Experiment i Ii Station Long- Term Effects of Dredging...Operations Program Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Effect of Food Ration on Sediment

  4. The development of a community and home-based chronic care management program for older adults.

    PubMed

    Cooper, Jennifer; McCarter, Kathryn A

    2014-01-01

    The objective of this paper was to evaluate a chronic care management program piloted by a visiting nurses association. Desired outcomes were to increase nurses' knowledge of self-management of chronic conditions and improve patient self-efficacy and clinical measures. The program provided educational development for nurses and piloted encounters with patients with chronic conditions targeting community health nurses for a chronic care professional (CCP) certification and invited 300 faith community nurses to an education program on chronic condition(s). Thirteen patients with chronic condition(s) were enrolled. Chronic care professional modules were used to increase nurses' knowledge and were measured by successful completion of a certification exam. Faith community nurses participated in an education program and completed a posttest to measure knowledge of content. Patient improvement in self-management was measured by pre- and postintervention self-efficacy scores and clinical measures. Seventeen nurses successfully completed the exam, and 38 faith community nurses participated in the program and completed the posttest. Three patients showed improvement in self-efficacy scores and eight in clinical measures. The educational development of community nurses prepared them to provide effective encounters to improve self-efficacy and clinical outcomes for older adults with chronic conditions. © 2013 Wiley Periodicals, Inc.

  5. Chronic tolerance to ethanol-induced sedation: implication for age-related differences in locomotor sensitization.

    PubMed

    Quoilin, Caroline; Didone, Vincent; Tirelli, Ezio; Quertemont, Etienne

    2013-06-01

    The adolescent brain has been suggested to be particularly sensitive to ethanol-induced neuroadaptations, which in turn could increase the risk of youths for alcohol abuse and dependence. Sensitization to the locomotor stimulant effects of ethanol has often been used as an animal model of ethanol-induced neuroadaptations. Previously, we showed that young mice were more sensitive than adults to the locomotor sensitization induced by high ethanol doses. However, this effect could be due to age-related differences in chronic tolerance to the sedative effects of ethanol. The aim of the present study is to assess chronic tolerance to the sedative effects of ethanol in weaning 21-day-old (P21), adolescent 35-day-old (P35) and adult 63-day-old (P63) female Swiss mice. After a daily injection of saline or 4 g/kg ethanol during 6 consecutive days, all P21, P35 and P63 mice were injected with 4 g/kg ethanol and submitted to the loss of righting reflex procedure. Our results confirm that the sensitivity to the acute sedative effects of ethanol gradually increases with age. Although this schedule of ethanol injections induces significant age-related differences in ethanol sensitization, it did not reveal significant differences between P21, P35 and P63 mice in the development of a chronic ethanol tolerance to its sedative effects. The present results show that age-related differences in the development of ethanol sensitization cannot be explained by differences in chronic ethanol tolerance to its sedative effects. More broadly, they do not support the idea that ethanol-induced sensitization is a by-product of chronic ethanol tolerance. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Effective physical treatment for chronic low back pain.

    PubMed

    Maher, C G

    2004-01-01

    It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future.

  7. The Efficacy of Systemic Lidocaine in the Management of Chronic Pain: A Literature Review.

    PubMed

    Yousefshahi, Fardin; Predescu, Oana; Francisco Asenjo, Juan

    2017-06-01

    Despite recent advances in the understanding of the chronic pain concept, its diagnosis and management remains a daily challenge for clinicians and patients. Based on the published literature, this review discusses and tries to organize the current knowledge and the up-to-date clinical experience about the efficacy and safety of the use of intravenous lidocaine in treatment and prevention of chronic pain. To prepare this narrative review, we performed an in depth literature review using the PubMed searching engine. We extracted all relevant articles published in English, up to April 2016. Lidocaine, administered as transdermal patch or intravenous lidocaine, is a safe and effective modality in the treatment of post-herpetic neuralgia (PHN), complex regional pain syndrome, as well and for prevention of chronic pain. It may be effective in the management of neuropathic pain syndromes, chronic pain, post-operative pain, and refractory cancer pain. Intravenous lidocaine and lidocaine patch are effective and safe for the treatment of several chronic or neuropathic pain syndromes. The use of lidocaine during surgery could prevent the development of some chronic post-surgical pain syndromes.

  8. The Chronic Care Model as vehicle for the development of disease management in Europe

    PubMed Central

    Spreeuwenberg, Cor

    2008-01-01

    The Chronic Care Model (Wagner, WHO) aims to improve the functioning and clinical situation of chronic patients by focussing on the patient, the practice team and the conditions that determine the functioning of the team. The patient is the most important actor who must be stimulated proactively by a competent, integrated practice team. Six interdependent conditional components are essential: health care organisation, delivery system design, community resources and policies, self-management support systems, decision support and clinical information systems. While the Chronic Care Model focuses on quality and effectiveness of care, disease management programmes underline more the efficiency of care. These programmes apply industrial management principles in health care. Information about process, structure and outcome is gathered and used systematically and human and material sources are used efficiently. There is evidence that the approaches of the Chronic Care Model and disease management can be integrated. Both approaches underline the need of information and focus on the patient as the main actor to improve and that a balance can be found between effectiveness and efficiency. Ideas will be given how the Chronic Care Model can be used as a framework for the development of a European way of disease management for people with a chronic condition.

  9. Mentorship and competencies for applied chronic disease epidemiology.

    PubMed

    Lengerich, Eugene J; Siedlecki, Jennifer C; Brownson, Ross; Aldrich, Tim E; Hedberg, Katrina; Remington, Patrick; Siegel, Paul Z

    2003-01-01

    To understand the potential and establish a framework for mentoring as a method to develop professional competencies of state-level applied chronic disease epidemiologists, model mentorship programs were reviewed, specific competencies were identified, and competencies were then matched to essential public health services. Although few existing mentorship programs in public health were identified, common themes in other professional mentorship programs support the potential of mentoring as an effective means to develop capacity for applied chronic disease epidemiology. Proposed competencies for chronic disease epidemiologists in a mentorship program include planning, analysis, communication, basic public health, informatics and computer knowledge, and cultural diversity. Mentoring may constitute a viable strategy to build chronic disease epidemiology capacity, especially in public health agencies where resource and personnel system constraints limit opportunities to recruit and hire new staff.

  10. Analysing the causes of chronic cough: relation to diesel exhaust, ozone, nitrogen oxides, sulphur oxides and other environmental factors

    PubMed Central

    Groneberg-Kloft, Beatrix; Kraus, Thomas; Mark, Anke van; Wagner, Ulrich; Fischer, Axel

    2006-01-01

    Air pollution remains a leading cause of many respiratory diseases including chronic cough. Although episodes of incidental, dramatic air pollution are relatively rare, current levels of exposure of pollutants in industrialized and developing countries such as total articles, diesel exhaust particles and common cigarette smoke may be responsible for the development of chronic cough both in children and adults. The present study analyses the effects of common environmental factors as potential causes of chronic cough. Different PubMed-based researches were performed that related the term cough to various environmental factors. There is some evidence that chronic inhalation of diesel can lead to the development of cough. For long-term exposure to nitrogen dioxide (NO2), children were found to exhibit increased incidences of chronic cough and decreased lung function parameters. Although a number of studies did not show that outdoor pollution directly causes the development of asthma, they have demonstrated that high levels pollutants and their interaction with sunlight produce ozone (O3) and that repeated exposure to it can lead to chronic cough. In summary, next to the well-known air pollutants which also include particulate matter and sulphur dioxide, a number of other indoor and outdoor pollutants have been demonstrated to cause chronic cough and therefore, environmental factors have to be taken into account as potential initiators of both adult and pediatric chronic cough. PMID:16722555

  11. New Developments in the Psychological Management of Chronic Pain.

    PubMed

    Morley, Stephen; Williams, Amanda

    2015-04-01

    After reviewing how psychological treatment for chronic pain comes to have its current form, and summarizing treatment effectiveness, we explore several areas of development. We describe third wave therapies, such as mindfulness; we discuss what the research literature aggregated can tell us about what trials are more useful to conduct; and we outline some areas of promise and some failures to deliver on promise. The article is drawn together using the framework of the normal psychology of pain, identifying some of its most important implications for improving life for people with chronic pain.

  12. Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats.

    PubMed

    Mattioli, Theresa-Alexandra M; Milne, Brian; Cahill, Catherine M

    2010-04-16

    The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance. Spinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration. Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone. This research provides further validation for using ultra-low dose opioid receptor antagonists in the treatment of various pain syndromes.

  13. HKF-R 10 - screening for predicting chronicity in acute low back pain (LBP): a prospective clinical trial.

    PubMed

    Neubauer, Eva; Junge, Astrid; Pirron, Peter; Seemann, Hanne; Schiltenwolf, Marcus

    2006-08-01

    Prospective cohort study. To develop a short instrument to reliably predict chronicity in low back pain (LBP). Health care expenditures on the treatment of low back pain continue to increase. It is therefore important to prevent the development of chronicity. In Germany, there is at present no early risk assessment tool to predict the risk of developing chronic LBP for patients presenting with acute LBP. Undertaken in an orthopedic practice setting, this study examined known risk factors for chronicity. It resulted in the development of a short questionnaire that successfully predicted the course of chronicity with an accuracy of 78%. A cohort of 192 orthopaedic outpatients was assessed for clinical, behavioral, emotional, and cognitive parameters bsed on a self-report test battery of 167 established items predictive for chronicity in LBP. Chronicity was defined as back pain persisting for longer than six months. Logistic regression analysis was performed to evaluate the predictive value of all items significantly associated with the dependent variable. The study found the following items to have the strongest predictive value in the development of chronicity: "How strong was your back pain during the last week when it was most tolerable?" and the question "How much residual pain would you be willing to tolerate while still considering the therapy successful?" These were followed by the variables for "Duration of existing LBP" (more than eight days), the patient's educational level (low levels are related to higher risks of chronicity) and pain being experienced elsewhere in the body. Other significant factors were five items assessing depression (Zung) and the palliative effect of therapeutic massage (where a positive correlation was found). Female patients have a higher risk for chronicity, as do patients with a high total score on the scales assessing "catastrophizing thoughts" and thoughts of "helplessness". Using the items listed above, the study was able to predict a patient's risk of developing chronic LBP with a probability of 78%. These items were assembled in a brief questionnaire and were paired with a corresponding evaluative tool. This enables practitioners to assess an individual patient's risk for chronicity by means of a simple calculator in just a few minutes. A validation study for the questionnaire is currently being prepared. MINI ABSTRACT: The objective of this study was the development of a brief questionnaire to assess the risk for chronicity for LBP.

  14. Combined endosulfan and cypermethrin-induced toxicity to embryo-larval development of Rhinella arenarum.

    PubMed

    Svartz, Gabriela V; Aronzon, Carolina M; Pérez Coll, Cristina S

    2016-01-01

    The combined effects of two widely used pesticides, endosulfan and cypermethrin, on survival of embryo-larval development of the South American toad (Rhinella arenarum) were examined. The toxicity bioassays were performed according to the AMPHITOX test. Embryos and larvae were exposed to mixtures of these pesticides at equitoxic ratios from acute or chronic exposure to evaluate interaction effects. The results were analyzed using both Marking's additive index and combination index (CI)-isobologram methods. Acute (96-h) and intermediate (168-h) toxicity of endosulfan-cypermethrin mixtures remained almost constant for larvae and embryos, but when exposure duration was increased, there was a significant elevation in toxicity, obtaining chronic (240-h) no-observed-effect concentrations (NOEC) values of 0.045 and 0.16 mg/L for embryos and larvae, respectively. These are environmentally relevant concentrations that reflect a realistic risk of this pesticide mixture to this native amphibian species. The toxicity increment with the exposure duration was coincident with the central nervous system development on embryos reaching the larval period, the main target organ of these pesticides. The interactions of the pesticide mixtures at acute and chronic exposure were antagonistic for embryo development (CI > 1), and additive (CI = 1) for larvae, while chronic exposure interactions were synergistic (CI < 1) for both developmental periods. Data indicated that endosulfan-cypermethrin mixtures resulted in different interaction types depending on duration and developmental stage exposed. As a general pattern and considering conditions of overall developmental period and chronic exposure, this pesticide mixture usually applied in Argentine crop fields is synergistic with respect to toxicity for this native amphibian species.

  15. [The Utilization of Health-Related Applications in Chronic Disease Self-Management].

    PubMed

    Kao, Chi-Wen; Chuang, Hui-Wan; Chen, Ting-Yu

    2017-08-01

    The dramatic increase in smartphone usage has spurred the development of many health-related mobile applications (apps). On the other hand, population aging and the associated rise in the incidence of chronic disease is increasing the demand for long-term care. Effective chronic disease self-management has been shown to help patients improve their health condition. Numerous smartphone applications currently support patient self-management of chronic disease, facilitating health management and health promotion. The purpose of the present article was to introduce the definition, contents, and types of health-related apps; to discuss the effectiveness of self-management health-related apps in promoting chronic disease management; and to assess and evaluate these apps. We hope that the present article helps give to healthcare professionals and patients who are willing to manage their diseases a general understanding of health-related apps and their potential to facilitate the self-management of chronic diseases.

  16. Chronic respiratory effects of exposure to diesel emissions in coal mines.

    PubMed

    Ames, R G; Hall, D S; Reger, R B

    1984-01-01

    A 5-yr prospective design was employed to test the hypothesis that exposure to diesel emissions leads to chronic respiratory effects among underground coal miners. Changes in respiratory function and development of chronic respiratory symptoms were measured during a 5-yr study period (i.e., 1977 to 1982) in 280 diesel-exposed and 838 control miners from Eastern and Western United States underground coal mines. Spirometry measures of respiratory function included forced expiratory volume in 1 sec (FEV1.0), forced vital capacity (FVC), and forced expiratory flow rate at 50% of FVC (FEF50). Chronic respiratory symptom measures, which included chronic cough, chronic phlegm, and breathlessness, were obtained by questionnaires, as were smoking status and occupational history. Based upon these data, the pattern of evidence did not support the hypothesis either in an age-adjusted comparison of diesel vs. nondiesel miners or in an internal analysis by cumulative years of diesel exposure.

  17. [Morphology and pathogenesis of visceral manifestations of chronic alcoholism].

    PubMed

    Lebedev, S P

    1982-01-01

    Chronic alcoholism is accompanied by systemic involvement of the internal organs. Clinico-morphological forms of chronic alcoholism are distinguished on the basis of the prevailing organ pathology, Morphological data are presented, and pathogenesis of the lesions of the liver, heart, pancreas, and kidneys in patients with chronic alcoholism is analysed. The hepatic form may present alcoholic dystrophy, hepatitis or cirrhosis which are stages of progressing hepatopathy. The toxic and metabolic effect of ethanol is important in the pathogenesis of liver lesion. The cardiac form is characterized by the development of alcoholic myocardiodystrophy. In addition to the toxic influence of ethanol, hormonal and electrolyte changes and microcirculatory disorders play a role in its pathogenesis. Chronic calcifying pancreatitis in chronic alcoholism is associated with the effect of ethanol on the mediatory system. The renal form any present necronephrosis, hepatorenal syndrome, glomerulonephritis or pyelonephritis. Their pathogenesis is determined by toxicity of ethanol, circulation of immune complexes in the blood, or immunosuppression.

  18. Aging and chronic alcohol consumption are determinants of p16 gene expression, genomic DNA methylation and p16 promoter methylation in the mouse colon

    USDA-ARS?s Scientific Manuscript database

    Elder age and chronic alcohol consumption are important risk factors for the development of colon cancer. Each factor can alter genomic and gene-specific DNA methylation. This study examined the effects of aging and chronic alcohol consumption on genomic and p16-specific methylation, and p16 express...

  19. Ageing, chronic alcohol consumption and folate are determinants of genomic DNA methylation, p16 promoter methylation and the expression of p16 in the mouse colon

    USDA-ARS?s Scientific Manuscript database

    Elder age and chronic alcohol consumption are important risk factors for the development of colon cancer. Each factor can alter genomic and gene-specific DNA methylation. This study examined the effects of aging and chronic alcohol consumption on genomic and p16-specific methylation, and p16 express...

  20. Continuous Exposure to Low-Dose-Rate Gamma Irradiation Reduces Airway Inflammation in Ovalbumin-Induced Asthma.

    PubMed

    Kim, Joong Sun; Son, Yeonghoon; Bae, Min Ji; Lee, Seung Sook; Park, Sun Hoo; Lee, Hae June; Lee, Soong In; Lee, Chang Geun; Kim, Sung Dae; Jo, Wol Soon; Kim, Sung Ho; Shin, In Sik

    2015-01-01

    Although safe doses of radiation have been determined, concerns about the harmful effects of low-dose radiation persist. In particular, to date, few studies have investigated the correlation between low-dose radiation and disease development. Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of low-dose-rate chronic irradiation on allergic asthma in a murine model. Mice were sensitized and airway-challenged with ovalbumin (OVA) and were exposed to continuous low-dose-rate irradiation (0.554 or 1.818 mGy/h) for 24 days after initial sensitization. The effects of chronic radiation on proinflammatory cytokines and the activity of matrix metalloproteinase-9 (MMP-9) were investigated. Exposure to low-dose-rate chronic irradiation significantly decreased the number of inflammatory cells, methylcholine responsiveness (PenH value), and the levels of OVA-specific immunoglobulin E, interleukin (IL)-4, and IL-5. Furthermore, airway inflammation and the mucus production in lung tissue were attenuated and elevated MMP-9 expression and activity induced by OVA challenge were significantly suppressed. These results indicate that low-dose-rate chronic irradiation suppresses allergic asthma induced by OVA challenge and does not exert any adverse effects on asthma development. Our findings can potentially provide toxicological guidance for the safe use of radiation and relieve the general anxiety about exposure to low-dose radiation.

  1. Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

    PubMed

    Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

    2017-09-29

    Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Hypercaloric diet modulates effects of chronic stress: a behavioral and biometric study on rats.

    PubMed

    Oliveira, Carla de; Oliveira, Cleverson Moraes de; de Macedo, Isabel Cristina; Quevedo, Alexandre S; Filho, Paulo Ricardo Marques; Silva, Fernanda Ribeiro da; Vercelino, Rafael; de Souza, Izabel C Custodio; Caumo, Wolnei; Torres, Iraci L S

    2015-01-01

    Obesity is a chronic disease that has been associated with chronic stress and hypercaloric diet (HD) consumption. Increased ingestion of food containing sugar and fat ingredients (comfort food) is proposed to "compensate" chronic stress effects. However, this eating habit may increase body fat depositions leading to obesity. This study evaluated behavioral/physiological parameters seeking to establish whether there is an association between the effects of HD intake and stress, and to test the hypothesis that the development of anxious behavior and obesity during chronic stress periods depends on the type of diet. Sixty-day-old male Wistar rats (n = 100) were divided into four groups: standard chow, hypercaloric diet, chronic stress/standard chow and chronic stress/hypercaloric diet. Chronic stress was induced by restraint stress exposure for 1 h/day, for 80 d. At the end of this period, rat behavior was evaluated using open-field and plus-maze tests. The results showed that HD alone increased weight gain and adipose deposition in subcutaneous and mesenteric areas. However, stress reduced weight gain and adipose tissue in these areas. HD also increased naso-anal length and concurrent stress prevented this. Behavioral data indicated that stress increased anxiety-like behaviors and comfort food reduced these anxiogenic effects; locomotor activity increased in rats fed with HD. Furthermore, HD decreased corticosterone levels and stress increased adrenal weight. The data indicate that when rats are given HD and experience chronic stress this association reduces the pro-obesogenic effects of HD, and decreases adrenocortical activity.

  3. Intervention Mapping to develop a Social Cognitive Theory-based intervention for chronic pain tailored to individuals with HIV.

    PubMed

    Merlin, Jessica S; Young, Sarah R; Johnson, Mallory O; Saag, Michael; Demonte, William; Kerns, Robert; Bair, Matthew J; Kertesz, Stefan; Turan, Janet M; Kilgore, Meredith; Clay, Olivio J; Pekmezi, Dorothy; Davies, Susan

    2018-06-01

    Chronic pain is an important comorbidity among individuals with HIV. Behavioral interventions are widely regarded as evidence-based, efficacious non-pharmacologic interventions for chronic pain in the general population. An accepted principle in behavioral science is that theory-based, systematically-developed behavioral interventions tailored to the unique needs of a target population are most likely to be efficacious. Our aim was to use Intervention Mapping to systematically develop a Social Cognitive Theory (SCT)-based intervention for chronic pain tailored to individuals with HIV that will improve pain intensity and pain-related functional impairment. Our Intervention Mapping process was informed by qualitative inquiry of 24 patients and seven providers in an HIV primary care clinic. The resulting intervention includes group and one-on-one sessions and peer and staff interventionists. We also developed a conceptual framework that integrates our qualitative findings with SCT-based theoretical constructs. Using this conceptual framework as a guide, our future work will investigate the intervention's impact on chronic pain outcomes, as well as our hypothesized proximal mediators of the intervention's effect.

  4. Natural products for chronic cough: Text mining the East Asian historical literature for future therapeutics.

    PubMed

    Shergis, Johannah Linda; Wu, Lei; May, Brian H; Zhang, Anthony Lin; Guo, Xinfeng; Lu, Chuanjian; Xue, Charlie Changli

    2015-08-01

    Chronic cough is a significant health burden. Patients experience variable benefits from over the counter and prescribed products, but there is an unmet need to provide more effective treatments. Natural products have been used to treat cough and some plant compounds such as pseudoephedrine from ephedra and codeine from opium poppy have been developed into drugs. Text mining historical literature may offer new insight for future therapeutic development. We identified natural products used in the East Asian historical literature to treat chronic cough. Evaluation of the historical literature revealed 331 natural products used to treat chronic cough. Products included plants, minerals and animal substances. These natural products were found in 75 different books published between AD 363 and 1911. Of the 331 products, the 10 most frequently and continually used products were examined, taking into consideration findings from contemporary experimental studies. The natural products identified are promising and offer new directions in therapeutic development for treating chronic cough. © The Author(s) 2015.

  5. Chronic alcohol consumption from adolescence-to-adulthood in mice--effect on growth and social behavior.

    PubMed

    Zou, Hong; Xie, Qinglian; Zhang, Manfang; Zhang, Chenghao; Zhao, Guoping; Jin, Meilei; Yu, Lei

    2009-09-01

    Experimentation with alcohol is common during adolescence. However the long-term consequences from moderate alcohol use during adolescence development are not clear. Using a two-bottle free-choice paradigm in the home-cage setting, we studied adolescent mice (4 weeks old) across a 6-week time span of the adolescence-to-adulthood development period. Adolescent mice readily reached a steady level of alcohol consumption and maintained this level throughout the 6-week period. Chronic alcohol consumption resulted in reduced growth in adolescent mice, as well as accelerated acclimation to a novel environment. During a social interaction test, similar levels of initial social investigation and subsequent habituation were observed in both the chronic alcohol and the water-only control groups. However, chronic alcohol self-administration resulted in impaired social recognition and decreased social play/fight behavior. Taken together, these results indicated that chronic alcohol consumption across adolescence development negatively impacted both physical growth and social behavior in mice, highlighting the detrimental consequences from prolonged alcohol drinking in adolescence.

  6. ETIB tests safety and effectiveness of Baricitinib for chronic GVHD | Center for Cancer Research

    Cancer.gov

    The Center for Cancer Research has launched a new clinical trial focusing on improving the treatment of chronic graft-versus-host disease, a common adverse reaction that may develop after certain bone marrow transplants.  Learn more...

  7. Derivatives of furanditerpenes from Pterodon genus: Pharmacological studies disclose their potential as chronic pain relief in mice.

    PubMed

    Spindola, Humberto M; Grando, Rogério; Figueiredo, Mariana C; Basting, Rosana; Queiroz, N C A; de Fátima, Ângelo; de Carvalho, João E; Wang, Zaijie J; Foglio, M A

    2017-06-05

    Pterodon genus fruits are commercially available at the Brazilian medicinal market used in folk medicine due to their anti-inflammatory, analgesic, and anti-rheumatic effects. Previous studies demonstrated that furanditerpenes possessing vouacapan skeleton, isolated from Pterodon genus, possess expressive antinociceptive activities, with promising moiety for the development of new analgesic products. The antinociceptive properties of compounds 6α,7β-6α-hidroxivouacapan-7β-17β-lactone (HVL) and 6α-oxovouacapan-7β-17β-lactone (OVL), semi-synthetic analogues of furanditerpenes previously reported as analgesic agents were evaluated on animal experimental models (Spindola et al., 2010, 2011). The chemical-induced pain methods used in the present work, demonstrated for the first time that both compounds HVL and OVL have potential as important templates for the development of chronic pain control drugs. The main findings of this work were that both compounds were: effective in the writhing test; reduced paw edema in the carrageenan test; effective in the inflammatory phase of the formalin test corroborating their activity against inflammatory pain conditions; effective on reducing pain through the stimulation of vanilloid receptors sensible to capsaicin (an important pathway for chronic pain maintenance); reduced the pain stimulus caused by PGE 2 injection (a pathway involved in chronic pain hypersensitivity); effective on decreasing mechanical allodynia in the CFA-model, demonstrating their potential use against chronic pain disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Marital Biography and Health at Mid-Life*

    PubMed Central

    Hughes, Mary Elizabeth; Waite, Linda J.

    2011-01-01

    This article develops a series of hypotheses about the long-term effects of one’s history of marriage, divorce, and widowhood on health, and it tests those hypotheses using data from the Health and Retirement Study. We examine four dimensions of health at mid-life: chronic conditions, mobility limitations, self-rated health, and depressive symptoms. We find that the experience of marital disruption damages health, with the effects still evident years later; among the currently married, those who have ever been divorced show worse health on all dimensions. Both the divorced and widowed who do not remarry show worse health than the currently married on all dimensions. Dimensions of health that seem to develop slowly, such as chronic conditions and mobility limitations, show strong effects of past marital disruption, whereas others, such as depressive symptoms, seem more sensitive to current marital status. Those who spent more years divorced or widowed show more chronic conditions and mobility limitations. PMID:19711810

  9. Paediatric chronic illness and educational failure: the role of emotional and behavioural problems.

    PubMed

    Layte, Richard; McCrory, Cathal

    2013-08-01

    Chronic illness in childhood is associated with worse educational outcomes. The association is usually explained via lowered cognitive development, decreased readiness to learn and school absence. However, this paper examines whether worse psychological adjustment may also play a role. We use data from the Growing Up in Ireland study, a cohort study, which collected data on 8,568 nine-year-old children through the Irish national school system using a two-stage sampling method. Maximum likelihood path analytic models are used to assess the direct effect of child chronic illness on reading and maths test scores and the mediating role of emotional and behavioural problems. In unadjusted analyses, children with a mental and behavioural condition scored 14.5 % points less on reading tests and 16.9 % points less on maths tests than their healthy peers. Children with non-mental and behavioural conditions scored 3 % points less on both tests, a significant difference. Mental and behavioural (OR, 9.58) and other chronic conditions (OR, 1.61) were significantly more likely to have 'high' levels of difficulties on the SDQ. Path analysis models showed that the association between chronic illness and educational test scores was completely mediated by emotional and behavioural problems controlling for school absence and bullying by peers. Child and adolescent chronic illness can have significant effects on educational development and a long-lasting impact on future life-chances. The psychological adjustment of the child is important in mediating the effect of chronic illness on educational outcomes. Interventions should target this developmental pathway.

  10. The Efficacy of Systemic Lidocaine in the Management of Chronic Pain: A Literature Review

    PubMed Central

    Yousefshahi, Fardin; Predescu, Oana; Francisco Asenjo, Juan

    2017-01-01

    Context Despite recent advances in the understanding of the chronic pain concept, its diagnosis and management remains a daily challenge for clinicians and patients. Based on the published literature, this review discusses and tries to organize the current knowledge and the up-to-date clinical experience about the efficacy and safety of the use of intravenous lidocaine in treatment and prevention of chronic pain. Evidence Acquisition To prepare this narrative review, we performed an in depth literature review using the PubMed searching engine. We extracted all relevant articles published in English, up to April 2016. Results Lidocaine, administered as transdermal patch or intravenous lidocaine, is a safe and effective modality in the treatment of post-herpetic neuralgia (PHN), complex regional pain syndrome, as well and for prevention of chronic pain. It may be effective in the management of neuropathic pain syndromes, chronic pain, post-operative pain, and refractory cancer pain. Conclusions Intravenous lidocaine and lidocaine patch are effective and safe for the treatment of several chronic or neuropathic pain syndromes. The use of lidocaine during surgery could prevent the development of some chronic post-surgical pain syndromes. PMID:28856112

  11. Development of a strontium chronic effects benchmark for aquatic life in freshwater.

    PubMed

    McPherson, Cathy A; Lawrence, Gary S; Elphick, James R; Chapman, Peter M

    2014-11-01

    There are no national water-quality guidelines for strontium for the protection of freshwater aquatic life in North America or elsewhere. Available data on the acute and chronic toxicity of strontium to freshwater aquatic life were compiled and reviewed. Acute toxicity was reported to occur at concentrations ranging from 75 mg/L to 15 000 mg/L. The majority of chronic effects occurred at concentrations above 11 mg/L; however, calculation of a representative benchmark was confounded by results from 4 studies indicating that chronic effects occurred at lower concentrations than all other studies, in 2 cases below background concentrations reported for US and European streams. Two of these studies, including 1 reporting effects below background concentrations, were repeated and found not to be reproducible; chronic effects occurred at considerably higher strontium concentrations than in the original studies. Studies with narrow-mouthed toad and goldfish were not repeated; both studies reported chronic effects below background concentrations, and both studies had been conducted by the authors of 1 of the 2 studies that were repeated and shown to be nonreproducible. Studies by these authors (3 of the 4 confounding studies), conducted over 30 yr ago, lacked detail in reporting of methods and results. It is thus likely that repeating the toad and goldfish studies would also have resulted in a higher strontium effects concentration. A strontium chronic effects benchmark of 10.7 mg/L that incorporates the results of additional testing summarized in the present study is proposed for freshwater environments. © 2014 SETAC.

  12. New Developments in the Psychological Management of Chronic Pain

    PubMed Central

    Morley, Stephen; Williams, Amanda

    2015-01-01

    After reviewing how psychological treatment for chronic pain comes to have its current form, and summarizing treatment effectiveness, we explore several areas of development. We describe third wave therapies, such as mindfulness; we discuss what the research literature aggregated can tell us about what trials are more useful to conduct; and we outline some areas of promise and some failures to deliver on promise. The article is drawn together using the framework of the normal psychology of pain, identifying some of its most important implications for improving life for people with chronic pain. PMID:26174216

  13. A possible link between dysmenorrhoea and the development of chronic pelvic pain.

    PubMed

    Hardi, Gemma; Evans, Susan; Craigie, Meredith

    2014-12-01

    Anecdotally, severe dysmenorrhoea can pre-date the development of chronic pelvic pain (CPP). This study describes the timeline for the transition from dysmenorrhoea to CPP in a cohort of new patients attending a private gynaecology clinic. In 16.4% of cases, transition occurred within one year, and within 12 years in over 50%. Our study suggests clinicians need to observe women with severe dysmenorrhoea for signs of chronic pain. Further research is needed into the transition from dysmenorrhoea to CPP, and effective early interventions. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  14. Insomnia, Sleep Duration, Depressive Symptoms, and the Onset of Chronic Multisite Musculoskeletal Pain.

    PubMed

    Generaal, Ellen; Vogelzangs, Nicole; Penninx, Brenda W J H; Dekker, Joost

    2017-01-01

    The temporal relationships among sleep, depressive symptoms, and pain are unclear. This longitudinal study examines whether insomnia and sleep duration predict the onset of chronic multisite musculoskeletal pain over 6 years and whether this association is mediated by depressive symptoms. 1860 subjects of the Netherlands Study of Depression and Anxiety, free from chronic multisite musculoskeletal pain at baseline, were followed up for the onset of chronic multisite musculoskeletal pain over 6 years (Chronic Pain Grade Questionnaire). We determined baseline insomnia (Women's Health Initiative Insomnia Rating Scale ≥9) and sleep duration (short: ≤6 hr, normal: 7-9 hr, long: ≥10 hr). Depressive symptoms were assessed at baseline and as a change score over time (Inventory of Depressive Symptomatology). Insomnia (hazard ratio [HR] [95% confidence interval, 95%CI] = 1.60 [1.30-1.96], p < .001) and short sleep duration (HR [95%CI] = 1.52 [1.22-1.90], p < .001) were associated with chronic pain onset. Adding baseline depressive symptoms as a mediator attenuated the associations for insomnia and short sleep with chronic pain onset (∆B = 40% and 26%, respectively). Adding the change score of depressive symptoms further weakened the association for insomnia (∆B = 16%) but not for short sleep. All direct effects for sleep measures with chronic pain onset remained statistically significant (p < .05). This longitudinal study shows that insomnia and short sleep duration are risk factors for developing chronic pain. Depressive symptoms partially mediate the effect for insomnia and short sleep with developing chronic pain. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  15. Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Interpretative Guidance for a Growth End Point

    DTIC Science & Technology

    1993-09-01

    carbohydrates from the worm’s internal musculature and transfer them to developing oocytes. In effect , the energy and metabolic 22 Chapter 4 Discussion...Miscellaneous Paper D-93-5 September 1993 US Army Corps AD-A269 836 of Engineers Waterways Experiment IIii l llli, Station Long- Term Effects of...Dredging Operations Program Chronic Sublethal Effects of San Francisco Bay Sediments on Nereis (Neanthes) arenaceodentata; Interpretative Guidance for a

  16. Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis.

    PubMed

    Łaski, Dariusz; Hać, Stanisław; Marek, Iwona; Kobiela, Jarosław; Kostro, Justyna; Adrych, Krystian; Śledziński, Zbigniew

    2018-03-01

    Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland - NFZ) and the national insurance system (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's duct within the Polish health care system. In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months.

  17. Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis

    PubMed Central

    Hać, Stanisław; Marek, Iwona; Kobiela, Jarosław; Kostro, Justyna; Adrych, Krystian; Śledziński, Zbigniew

    2018-01-01

    Introduction Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland – NFZ) and the national insurance system (Poland – ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. Aim The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung’s duct within the Polish health care system. Results In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. Conclusions From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months. PMID:29643954

  18. Honey and Cancer: Sustainable Inverse Relationship Particularly for Developing Nations—A Review

    PubMed Central

    Othman, Nor Hayati

    2012-01-01

    Honey and cancer has a sustainable inverse relationship. Carcinogenesis is a multistep process and has multifactorial causes. Among these are low immune status, chronic infection, chronic inflammation, chronic non healing ulcers, obesity, and so forth. There is now a sizeable evidence that honey is a natural immune booster, natural anti-inflammatory agent, natural antimicrobial agent, natural cancer “vaccine,” and natural promoter for healing chronic ulcers and wounds. Though honey has substances of which the most predominant is a mixture of sugars, which itself is thought to be carcinogenic, it is understandable that its beneficial effect as anticancer agent raises skeptics. The positive scientific evidence for anticancer properties of honey is growing. The mechanism on how honey has anticancer effect is an area of great interest. Among the mechanisms suggested are inhibition of cell proliferation, induction of apoptosis, and cell-cycle arrest. Honey and cancer has sustainable inverse relationship in the setting of developing nations where resources for cancer prevention and treatment are limited. PMID:22761637

  19. [Development of Empowerment Program for Persons with Chronic Mental Illness and Evaluation of Impact].

    PubMed

    Kim, Mijung; Lee, Kyunghee

    2015-12-01

    This study was done to develop an empowerment program for people with chronic mental illness and to analyze effects of the program on level of empowerment. The research was conducted using a nonequivalent control group pretest-posttest design. Participants were 37 people with chronic mental illness (experimental group: 18, control group: 19). The empowerment program was provided for 8 weeks (15 sessions). Data were collected between July 21 and October 17, 2014. Data were analyzed using Chi-square, Fisher's exact test, Sapiro-Wilk test, and Repeated measure ANOVA with SPSS/WIN 18.0. Quantitative results show that self-efficacy, interpersonal relationships, attitudes in the workplace, occupational performance capacity, and levels of empowered execute were significantly better in the experimental group compared to the control group. Study findings indicate that this empowerment program for persons with chronic mental illness is effective for improving self efficacy, interpersonal skills, attitudes in the workplace, occupational performance capacity, levels of empowered execute.

  20. Study protocol of EMPOWER participatory action research (EMPOWER-PAR): a pragmatic cluster randomised controlled trial of multifaceted chronic disease management strategies to improve diabetes and hypertension outcomes in primary care.

    PubMed

    Ramli, Anis S; Lakshmanan, Sharmila; Haniff, Jamaiyah; Selvarajah, Sharmini; Tong, Seng F; Bujang, Mohamad-Adam; Abdul-Razak, Suraya; Shafie, Asrul A; Lee, Verna K M; Abdul-Rahman, Thuhairah H; Daud, Maryam H; Ng, Kien K; Ariffin, Farnaza; Abdul-Hamid, Hasidah; Mazapuspavina, Md-Yasin; Mat-Nasir, Nafiza; Miskan, Maizatullifah; Stanley-Ponniah, Jaya P; Ismail, Mastura; Chan, Chun W; Abdul-Rahman, Yong R; Chew, Boon-How; Low, Wilson H H

    2014-09-13

    Chronic disease management presents enormous challenges to the primary care workforce because of the rising epidemic of cardiovascular risk factors. The chronic care model was proven effective in improving chronic disease outcomes in developed countries, but there is little evidence of its effectiveness in developing countries. The aim of this study was to evaluate the effectiveness of the EMPOWER-PAR intervention (multifaceted chronic disease management strategies based on the chronic care model) in improving outcomes for type 2 diabetes mellitus and hypertension using readily available resources in the Malaysian public primary care setting. This paper presents the study protocol. A pragmatic cluster randomised controlled trial using participatory action research is underway in 10 public primary care clinics in Selangor and Kuala Lumpur, Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Each clinic consecutively recruits type 2 diabetes mellitus and hypertension patients fulfilling the inclusion and exclusion criteria over a 2-week period. The EMPOWER-PAR intervention consists of creating/strengthening a multidisciplinary chronic disease management team, training the team to use the Global Cardiovascular Risks Self-Management Booklet to support patient care and reinforcing the use of relevant clinical practice guidelines for management and prescribing. For type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving HbA1c < 6.5%. For hypertension without type 2 diabetes mellitus, the primary outcome is the change in the proportion of patients achieving blood pressure < 140/90 mmHg. Secondary outcomes include the proportion of patients achieving targets for serum lipid profile, body mass index and waist circumference. Other outcome measures include medication adherence levels, process of care and prescribing patterns. Patients' assessment of their chronic disease care and providers' perceptions, attitudes and perceived barriers in care delivery and cost-effectiveness of the intervention are also evaluated. Results from this study will provide objective evidence of the effectiveness and cost-effectiveness of a multifaceted intervention based on the chronic care model in resource-constrained public primary care settings. The evidence should instigate crucial primary care system change in Malaysia. ClinicalTrials.gov NCT01545401.

  1. [CHRONIC FLUORIDE INTOXICATION AS A RISK FACTOR FOR THE DEVELOPMENT OF ATHEROSCLEROSIS].

    PubMed

    Korotenko, O Yu; Panev, N I; Zakharenkov, V V; Filimonov, S N; Semenova, E A; Panev, R N

    2015-01-01

    In workers employed in the aluminum industry, the main harmful production factor is exposure to fluoride salts, which can cause chronic fluoride intoxication. For the assessment of the impact of chronic fluoride intoxication on the development of atherosclerosis, we conducted a comprehensive survey of 87 aluminum-metal makers with chronic fluoride intoxication and 43 aluminum-metal makers without occupational diseases, mean age--52.1 ± 0.4 years. There were considered the presence and severity of atherosclerosis of brachiocephalic arteries, and the arteries of the lower extremities in the studied group, there was evaluated the effect of other risk factors for atherosclerosis (smoking, presence of hypertension, diabetes, dyslipidemia). With the use of Doppler ultrasound of the arteries it was revealed that in metallurgists with chronic fluoride intoxication atherosclerosis was detected in 73.6% versus 55.8% in persons of the comparison group. The performed analysis of the prevalence of main risk factors for atherosclerosis showed that in metal makers with chronic fluoride intoxication in combination with atherosclerosis hypertension is more common (in 54.7%) than in metallurgists with chronic fluoride intoxication without atherosclerosis--only 26.1%. According to the frequency of occurrence of smoking, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia, there were no significant differences between the metallurgists with chronic fluoride intoxication, with and without atherosclerosis, and the control group, the increase in LDL cholesterol occurs significantly more often in metal-makers with chronic fluoride intoxication in combination with atherosclerosis if compared to workers without occupational diseases. Thus, chronic fluoride intoxication acts as a risk factor in the development of atherosclerosis: atherosclerosis in metal-makers with chronic fluoride intoxication occurs more frequently than in workers who do not have professional pathology. Hypertension and elevated levels of LDL cholesterol were established to increase the relative risk of developing atherosclerosis in metallurgists with chronic fluoride intoxication. At that there are no significant differences in the prevalence of common risk factors for atherosclerosis (smoking, diabetes, hypercholesterolemia, hypertriglyceridemia).

  2. Sex differences in antinociceptive tolerance to delta-9-tetrahydrocannabinol in the rat

    PubMed Central

    Wakley, Alexa A.; Wiley, Jenny L.; Craft, Rebecca M.

    2014-01-01

    Background Sex differences in cannabinoid effects have been reported in rodents, with adult females typically being more sensitive than adult males. The present study compared the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) in adult, gonadally intact female vs. male rats. Methods Cumulative dose-effect curves were obtained for THC (1.0–18 mg/kg i.p.) on warm water tail withdrawal and paw pressure tests. Vehicle or the sex-specific ED80 dose for THC was administered twice daily for 9 days; THC dose-effect curves were then re-determined. Results On the pre-chronic test day, THC was significantly more potent in females than males in producing antinociception on the tail withdrawal and paw pressure tests. After 9 days of twice-daily THC treatment (5.4 mg/kg/injection in females, 7.6 mg/kg/injection in males), THC potency on both tests decreased more in females than males. On the tail withdrawal test, chronic THC produced 4.2- vs. 2.8-fold increases in ED50 values in females vs. males, respectively. On the paw pressure test, chronic THC produced 4.4- vs. 2.9-fold increases in ED50 values in females vs. males, respectively. Chronic THC treatment did not significantly disrupt estrous cycling in females. Conclusions These results demonstrate that – even when sex differences in acute THC potency are controlled for – females develop more antinociceptive tolerance to THC than males. Given the importance of drug tolerance in the development of drug dependence, these results suggest that females may be more vulnerable than males to developing dependence after chronic cannabinoid exposure. PMID:25131716

  3. Development and Validation of an Online Program for Promoting Self-Management among Korean Patients with Chronic Hepatitis B.

    PubMed

    Yang, Jinhyang

    2013-01-01

    The hepatitis B virus is second only to tobacco as a known human carcinogen. However, chronic hepatitis B usually does not produce symptoms and people feel healthy even in the early stages of live cancer. Therefore, chronically infected people should perceive it as a serious health problem and move on to appropriate health behaviour. The purpose of this paper is to develop and validate an online program for promoting self-management among Korean patients with chronic hepatitis B. The online program was developed using a prototyping approach and system developing life cycle method, evaluated by users for their satisfaction with the website and experts for the quality of the site. To evaluate the application of the online program, knowledge and self-management compliance of the subjects were measured and compared before and after the application of the online program. There were statistically significant increases in knowledge and self-management compliance in the user group. An online program with high accessibility and applicability including information, motivation, and behavior skill factors can promote self-management of the patient with chronic hepatitis B. Findings from this study allow Korean patients with chronic hepatitis B to engage in proactive and effective health management in the community or clinical practice.

  4. Chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring of the striatum

    PubMed Central

    Taylor, S.B.; Anglin, J.M.; Paode, P.R.; Riggert, A.G.; Olive, M.F.; Conrad, C.D.

    2014-01-01

    Chronic stress is an established risk factor in the development of addiction. Addiction is characterized by a progressive transition from casual drug use to habitual and compulsive drug use. The ability of chronic stress to facilitate the transition to addiction may be mediated by increased engagement of the neurocircuitries underlying habitual behavior and addiction. In the present study, striatal morphology was evaluated after two weeks of chronic variable stress in male Sprague-Dawley rats. Dendritic complexity of medium spiny neurons was visualized and quantified with Golgi staining in the dorsolateral and dorsomedial striatum, as well as in the nucleus accumbens core and shell. In separate cohorts, the effects of chronic stress on habitual behavior and the acute locomotor response to methamphetamine were also assessed. Chronic stress resulted in increased dendritic complexity in the dorsolateral striatum and nucleus accumbens core, regions implicated in habitual behavior and addiction, while decreased complexity was found in the nucleus accumbens shell, a region critical for the initial rewarding effects of drugs of abuse. Chronic stress did not affect dendritic complexity in the dorsomedial striatum. A parallel shift toward habitual learning strategies following chronic stress was also identified. There was an initial reduction in acute locomotor response to methamphetamine, but no lasting effect as a result of chronic stress exposure. These findings suggest that chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring in the striatum. PMID:25242641

  5. Management of recurrent depression.

    PubMed

    Howell, Cate; Marshall, Charlotte; Opolski, Melissa; Newbury, Wendy

    2008-09-01

    Depression is a potentially recurring or chronic disorder. The provision of evidence based treatment and effective practice organisation is central to chronic disease management, and these principles can be applied to managing depression. This article outlines the principles of chronic disease management, including the use of management plans and a team care approach, and their application to the management of depression. Treatment approaches that systematically assist patients in managing their chronic disease are more effective than those based on acute care. Depression treatment guidelines are available, as well as primary care initiatives which facilitate comprehensive and long term mental health care, including relapse prevention strategies. A number of risk factors for depression relapse have been identified, and research has recommended that novel intensive relapse prevention programs need to be developed.

  6. Disease management positively affects patient quality of life.

    PubMed

    Walker, David R; Landis, Darryl L; Stern, Patricia M; Vance, Richard P

    2003-04-01

    Health care costs are spiraling upward. The population of the United States is aging, and many baby boomers will develop multiple chronic health conditions. Disease management is one method for reducing costs associated with chronic health conditions. Although these programs have been proven effective in improving patient health, detailed information about their effect on patient quality of life has been scarce. This article provides preliminary evidence that disease management programs for coronary artery disease, chronic obstructive pulmonary disease, diabetes, and heart failure lead to improved quality of life, which correlates with a healthier, more satisfied, and less costly patient.

  7. Effects of short- and long-term exposures to copper on lethal and reproductive endpoints of the harpacticoid copepod Tigriopus fulvus.

    PubMed

    Biandolino, Francesca; Parlapiano, Isabella; Faraponova, Olga; Prato, Ermelinda

    2018-01-01

    The long-term exposure provides a realistic measurement of the effects of toxicants on aquatic organisms. The harpacticoid copepod Tigriopus fulvus has a wide geographical distribution and is considered as an ideal model organism for ecotoxicological studies for its good sensitivity to different toxicants. In this study, acute, sub-chronic and chronic toxicity tests based on lethal and reproductive responses of Tigriopus fulvus to copper were performed. The number of moults during larval development was chosen as an endpoint for sub-chronic test. Sex ratio, inhibitory effect on larval development, hatching time, fecundity, brood number, nauplii/brood, total newborn production, etc, were calculated in the chronic test (28d). Lethal effect of copper to nauplii showed the LC50-48h of 310 ± 72µgCu/L (mean ± sd). It was observed a significant inhibition of larval development at sublethal copper concentrations, after 4 and 7 d. After 4d, the EC50 value obtained for the endpoint in "moult naupliar reduction" was of 55.8 ± 2.5µgCu/L (mean ± sd). The EC50 for the inhibition of naupliar development into copepodite stage, was of 21.7 ± 4.4µgCu/L (mean ± sd), after 7 days. Among the different traits tested, copper did not affect sex ratio and growth, while fecundity and total nauplii production were the most sensitive endpoints. The reproductive endpoints offer the advantage of being detectable at very low pollutant concentrations. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Age-associated chronic diseases require age-old medicine: role of chronic inflammation.

    PubMed

    Prasad, Sahdeo; Sung, Bokyung; Aggarwal, Bharat B

    2012-05-01

    Most chronic diseases--such as cancer, cardiovascular disease (CVD), Alzheimer disease, Parkinson disease, arthritis, diabetes and obesity--are becoming leading causes of disability and death all over the world. Some of the most common causes of these age-associated chronic diseases are lack of physical activity, poor nutrition, tobacco use, and excessive alcohol consumption. All the risk factors linked to these chronic diseases have been shown to up-regulate inflammation. Therefore, downregulation of inflammation-associated risk factors could prevent or delay these age-associated diseases. Although modern science has developed several drugs for treating chronic diseases, most of these drugs are enormously expensive and are associated with serious side effects and morbidity. In this review, we present evidence on how chronic inflammation leads to age-associated chronic disease. Furthermore, we discuss diet and lifestyle as solutions for age-associated chronic disease. Published by Elsevier Inc.

  9. A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions.

    PubMed

    Ding, Cody; Zhang, Jingqiu; Yang, Dong

    2018-01-01

    In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions.

  10. Surgical Management of Chronic Pancreatitis.

    PubMed

    Parekh, Dilip; Natarajan, Sathima

    2015-10-01

    Advances over the past decade have indicated that a complex interplay between environmental factors, genetic predisposition, alcohol abuse, and smoking lead towards the development of chronic pancreatitis. Chronic pancreatitis is a complex disorder that causes significant and chronic incapacity in patients and a substantial burden on the society. Major advances have been made in the etiology and pathogenesis of this disease and the role of genetic predisposition is increasingly coming to the fore. Advances in noninvasive diagnostic modalities now allow for better diagnosis of chronic pancreatitis at an early stage of the disease. The impact of these advances on surgical treatment is beginning to emerge, for example, patients with certain genetic predispositions may be better treated with total pancreatectomy versus lesser procedures. Considerable controversy remains with respect to the surgical management of chronic pancreatitis. Modern understanding of the neurobiology of pain in chronic pancreatitis suggests that a window of opportunity exists for effective treatment of the intractable pain after which central sensitization can lead to an irreversible pain syndrome in patients with chronic pancreatitis. Effective surgical procedures exist for chronic pancreatitis; however, the timing of surgery is unclear. For optimal treatment of patients with chronic pancreatitis, close collaboration between a multidisciplinary team including gastroenterologists, surgeons, and pain management physicians is needed.

  11. The association of childhood trauma and personality disorders with chronic depression: A cross-sectional study in depressed outpatients.

    PubMed

    Klein, Jan Philipp; Roniger, Antje; Schweiger, Ulrich; Späth, Christina; Brodbeck, Jeannette

    2015-06-01

    Chronic depression has often been associated with childhood trauma. There may, however, be an interaction between personality pathology, childhood trauma, and chronic depression. This interaction has not yet been studied. This retrospective analysis is based on 279 patients contacted for a randomized trial in an outpatient psychotherapy center over a period of 18 months from 2010 to 2012. Current diagnoses of a personality disorder and presence of chronic depression were systematically assessed using the Structured Clinical Interview for DSM-IV. Retrospective reports of childhood trauma were collected using the short form of the Childhood Trauma Questionnaire (CTQ-SF). DSM-IV-defined chronic depression was the primary outcome. The association between chronic depression, childhood trauma, and personality disorders was analyzed using correlations. Variables that had at least a small effect on correlation analysis were entered into a series of logistic regression analyses to determine the predictors of chronic depression and the moderating effect of childhood trauma. The presence of avoidant personality disorder, but no CTQ-SF scale, was associated with the chronicity of depression (odds ratio [OR] = 2.20, P = .015). The emotional abuse subscale of the CTQ-SF did, however, correlate with avoidant personality disorder (OR = 1.15, P = .000). The level of emotional abuse had a moderating effect on the effect of avoidant personality disorder on the presence of chronic depression (OR = 1.08, P = .004). Patients who did not suffer from avoidant personality disorder had a decreased rate of chronic depression if they retrospectively reported more severe levels of emotional abuse (18.9% vs 39.7%, respectively). The presence of avoidant personality pathology may interact with the effect of childhood trauma in the development of chronic depression. This has to be confirmed in a prospective study. ClinicalTrials.gov identifier: NCT01226238. © Copyright 2015 Physicians Postgraduate Press, Inc.

  12. Development of the Chronic Pain Coding System (CPCS) for Characterizing Patient-Clinician Discussions About Chronic Pain and Opioids

    PubMed Central

    Chen, Meng; Matthias, Marianne S.; Bell, Robert A.; Kravitz, Richard L.

    2016-01-01

    Objective. To describe the development and initial application of the Chronic Pain Coding System. Design. Secondary analysis of data from a randomized clinical trial. Setting. Six primary care clinics in northern California. Subjects. Forty-five primary care visits involving 33 clinicians and 45 patients on opioids for chronic noncancer pain. Methods. The authors developed a structured coding system to accurately and objectively characterize discussions about pain and opioids. Two coders applied the final system to visit transcripts. Intercoder agreement for major coding categories was moderate to substantial (kappa = 0.5–0.7). Mixed effects regression was used to test six hypotheses to assess preliminary construct validity. Results. Greater baseline pain interference was associated with longer pain discussions (P = 0.007) and more patient requests for clinician action (P = 0.02) but not more frequent negative patient evaluations of pain (P = 0.15). Greater clinician-reported visit difficulty was associated with more frequent disagreements with clinician recommendations (P = 0.003) and longer discussions of opioid risks (P = 0.049) but not more frequent requests for clinician action (P = 0.11). Rates of agreement versus disagreement with patient requests and clinician recommendations were similar for opioid-related and non-opioid–related utterances. Conclusions. This coding system appears to be a reliable and valid tool for characterizing patient-clinician communication about opioids and chronic pain during clinic visits. Objective data on how patients and clinicians discuss chronic pain and opioids are necessary to identify communication patterns and strategies for improving the quality and productivity of discussions about chronic pain that may lead to more effective pain management and reduce inappropriate opioid prescribing. PMID:26936453

  13. Development of the Chronic Pain Coding System (CPCS) for Characterizing Patient-Clinician Discussions About Chronic Pain and Opioids.

    PubMed

    Henry, Stephen G; Chen, Meng; Matthias, Marianne S; Bell, Robert A; Kravitz, Richard L

    2016-10-01

    To describe the development and initial application of the Chronic Pain Coding System. Secondary analysis of data from a randomized clinical trial. Six primary care clinics in northern California. Forty-five primary care visits involving 33 clinicians and 45 patients on opioids for chronic noncancer pain. The authors developed a structured coding system to accurately and objectively characterize discussions about pain and opioids. Two coders applied the final system to visit transcripts. Intercoder agreement for major coding categories was moderate to substantial (kappa = 0.5-0.7). Mixed effects regression was used to test six hypotheses to assess preliminary construct validity. Greater baseline pain interference was associated with longer pain discussions (P = 0.007) and more patient requests for clinician action (P = 0.02) but not more frequent negative patient evaluations of pain (P = 0.15). Greater clinician-reported visit difficulty was associated with more frequent disagreements with clinician recommendations (P = 0.003) and longer discussions of opioid risks (P = 0.049) but not more frequent requests for clinician action (P = 0.11). Rates of agreement versus disagreement with patient requests and clinician recommendations were similar for opioid-related and non-opioid-related utterances. This coding system appears to be a reliable and valid tool for characterizing patient-clinician communication about opioids and chronic pain during clinic visits. Objective data on how patients and clinicians discuss chronic pain and opioids are necessary to identify communication patterns and strategies for improving the quality and productivity of discussions about chronic pain that may lead to more effective pain management and reduce inappropriate opioid prescribing. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Beyond interferon: rationale and prospects for newer treatment paradigms for chronic hepatitis C

    PubMed Central

    Cortez, Karoll J.

    2015-01-01

    Hepatitis C virus (HCV) infection results in a chronic carrier state in 80% of individuals infected with the virus and presently affects over 170 million people worldwide. Approximately 20% of those chronically infected will ultimately progress to develop cirrhosis and death due to end-stage liver disease or hepatocellular carcinoma (HCC). Unlike many other chronic viral infections, effective treatments for HCV are available. Cure from the infection is known as a sustained virologic response (SVR). SVR is associated with reversal of the long-term outcomes of chronic liver disease, decrease in incidence of HCC, and decrease HCV attributable mortality. The current FDA approved therapies for hepatitis C virus genotype 1 (GT-1) include pegylated interferon (PEG-IFN) and ribavirin (RBV) in combination with a directly acting antiviral agent (DAA). New therapeutic advances are being made aiming to simplify management, improve the tolerability of treatment, and shorten the duration of therapy. Moreover, treatment regimens that will effectively eradicate hepatitis C without the use of interferon formulations (IFN) are being developed. In this review, we report the transition of HCV therapeutics from an interferon-α based combination therapy to an all-oral, directly acting antiviral therapy. PMID:25553238

  15. Persistent and Newly Developed Chronic Bronchitis Are Associated with Worse Outcomes in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Zhao, Huaqing; Boriek, Aladin M.; Anzueto, Antonio; Soler, Xavier; Bhatt, Surya P.; Rennard, Stephen I.; Wise, Robert; Comellas, Alejandro; Ramsdell, Joe W.; Kinney, Gregory L.; Han, MeiLan K.; Martinez, Carlos H.; Yen, Andrew; Black-Shinn, Jennifer; Porszasz, Janos; Criner, Gerard J.; Hanania, Nicola A.; Sharafkhaneh, Amir; Crapo, James D.; Make, Barry J.; Silverman, Edwin K.; Curtis, Jeffrey L.

    2016-01-01

    Rationale: Chronic bronchitis is, by definition, a chronic condition, but the development and remission of this condition in cigarette smokers with or without chronic obstructive pulmonary disease (COPD) are poorly understood. Also, it is unclear how the persistence or new development of chronic bronchitis affects symptoms and outcomes. Objectives: To ascertain the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes. Methods: We analyzed 1,775 current or ex-smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0–IV COPD in phase 2 of the Genetic Epidemiology of COPD (COPDGene) Study, which included subjects after 5 years of follow-up from phase 1. We asked subjects at enrollment and at 5 years of follow-up about symptoms consistent with chronic bronchitis. We divided subjects into four groups: persistent chronic bronchitis– (negative at phase 1/negative at phase 2), resolved chronic bronchitis (positive/negative), new chronic bronchitis (negative/positive), and persistent chronic bronchitis+ (positive/positive). We analyzed respiratory symptoms, health-related quality of life, lung function, exacerbation frequency, and 6-minute walk distance. Measurements and Main Results: Compared with the persistent chronic bronchitis– group, members of the persistent chronic bronchitis+ group were more likely to have continued smoking (53.4%). Subjects with new chronic bronchitis were more likely to have resumed (6.6%) or continued smoking (45.6%), whereas subjects with resolved chronic bronchitis were more likely to have quit smoking (23.5%). Compared with the persistent chronic bronchitis– group, the other groups had a shorter 6-minute walk distance, worse lung function, greater exacerbation frequency, and worse respiratory symptoms. Modified Medical Research Council dyspnea and St. George’s Respiratory Questionnaire scores worsened between phase 1 and phase 2 in subjects with new chronic bronchitis but improved in the resolved chronic bronchitis group. On multinomial logistic regression, quitting smoking conferred an odds ratio (OR) of 4.289 (95% confidence interval [CI], 2.689–6.842) for resolved chronic bronchitis, whereas resuming smoking had an OR of 4.585 (95% CI, 2.008–10.471) for new chronic bronchitis. Persistent smoking had an OR of 2.621 (95% CI, 1.677–4.096) and 5.767 (95% CI, 3.702–8.983) for subjects with new chronic bronchitis and subjects with persistent chronic bronchitis, respectively. Conclusions: Persistent and newly developed chronic bronchitis are associated with continued or resumed smoking, greater respiratory symptoms, worse health-related quality of life, worse lung function, and greater exacerbation frequency. These findings stress the importance of repeatedly assessing chronic cough and sputum production in smokers to identify those at risk for poor outcomes. PMID:27158740

  16. Persistent and Newly Developed Chronic Bronchitis Are Associated with Worse Outcomes in Chronic Obstructive Pulmonary Disease.

    PubMed

    Kim, Victor; Zhao, Huaqing; Boriek, Aladin M; Anzueto, Antonio; Soler, Xavier; Bhatt, Surya P; Rennard, Stephen I; Wise, Robert; Comellas, Alejandro; Ramsdell, Joe W; Kinney, Gregory L; Han, MeiLan K; Martinez, Carlos H; Yen, Andrew; Black-Shinn, Jennifer; Porszasz, Janos; Criner, Gerard J; Hanania, Nicola A; Sharafkhaneh, Amir; Crapo, James D; Make, Barry J; Silverman, Edwin K; Curtis, Jeffrey L

    2016-07-01

    Chronic bronchitis is, by definition, a chronic condition, but the development and remission of this condition in cigarette smokers with or without chronic obstructive pulmonary disease (COPD) are poorly understood. Also, it is unclear how the persistence or new development of chronic bronchitis affects symptoms and outcomes. To ascertain the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes. We analyzed 1,775 current or ex-smokers with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0-IV COPD in phase 2 of the Genetic Epidemiology of COPD (COPDGene) Study, which included subjects after 5 years of follow-up from phase 1. We asked subjects at enrollment and at 5 years of follow-up about symptoms consistent with chronic bronchitis. We divided subjects into four groups: persistent chronic bronchitis- (negative at phase 1/negative at phase 2), resolved chronic bronchitis (positive/negative), new chronic bronchitis (negative/positive), and persistent chronic bronchitis+ (positive/positive). We analyzed respiratory symptoms, health-related quality of life, lung function, exacerbation frequency, and 6-minute walk distance. Compared with the persistent chronic bronchitis- group, members of the persistent chronic bronchitis+ group were more likely to have continued smoking (53.4%). Subjects with new chronic bronchitis were more likely to have resumed (6.6%) or continued smoking (45.6%), whereas subjects with resolved chronic bronchitis were more likely to have quit smoking (23.5%). Compared with the persistent chronic bronchitis- group, the other groups had a shorter 6-minute walk distance, worse lung function, greater exacerbation frequency, and worse respiratory symptoms. Modified Medical Research Council dyspnea and St. George's Respiratory Questionnaire scores worsened between phase 1 and phase 2 in subjects with new chronic bronchitis but improved in the resolved chronic bronchitis group. On multinomial logistic regression, quitting smoking conferred an odds ratio (OR) of 4.289 (95% confidence interval [CI], 2.689-6.842) for resolved chronic bronchitis, whereas resuming smoking had an OR of 4.585 (95% CI, 2.008-10.471) for new chronic bronchitis. Persistent smoking had an OR of 2.621 (95% CI, 1.677-4.096) and 5.767 (95% CI, 3.702-8.983) for subjects with new chronic bronchitis and subjects with persistent chronic bronchitis, respectively. Persistent and newly developed chronic bronchitis are associated with continued or resumed smoking, greater respiratory symptoms, worse health-related quality of life, worse lung function, and greater exacerbation frequency. These findings stress the importance of repeatedly assessing chronic cough and sputum production in smokers to identify those at risk for poor outcomes.

  17. Identification and Management of Chronic Pain in Primary Care: a Review.

    PubMed

    Mills, Sarah; Torrance, Nicola; Smith, Blair H

    2016-02-01

    Chronic pain is a common, complex, and challenging condition, where understanding the biological, social, physical and psychological contexts is vital to successful outcomes in primary care. In managing chronic pain the focus is often on promoting rehabilitation and maximizing quality of life rather than achieving cure. Recent screening tools and brief intervention techniques can be effective in helping clinicians identify, stratify and manage both patients already living with chronic pain and those who are at risk of developing chronic pain from acute pain. Frequent assessment and re-assessment are key to ensuring treatment is appropriate and safe, as well as minimizing and addressing side effects. Primary care management should be holistic and evidence-based (where possible) and incorporates both pharmacological and non-pharmacological approaches, including psychology, self-management, physiotherapy, peripheral nervous system stimulation, complementary therapies and comprehensive pain-management programmes. These may either be based wholly in primary care or supported by appropriate specialist referral.

  18. Evaluating peer teaching about chronic disease.

    PubMed

    Guenther, Sylvia; Shadbolt, Narelle; Roberts, Chris; Clark, Tyler

    2014-12-01

    The primary care areas of priority (PCAP) activity was developed to engage medical students in learning about chronic disease management in a clinical context from their peers. It is one of several summative assessment tasks that occur during a primary care community term rotation in a graduate-entry medical programme. We evaluated the acceptability and effectiveness of the PCAP activity as a combined teaching, learning and assessment innovation. Evaluation and assessment data from students who rotated through the four community term blocks during the 2011-2012 academic year was analysed using both qualitative and quantitative methods. PCAP peer teaching activity is an effective format for teaching about the management of chronic conditions in the community Analysis indicated that 89 per cent (n = 148/166) of responding students rated the PCAP as satisfactory, good or excellent. The marking rubric contained 11 assessable components, including teaching skills, mastery of clinical knowledge, developing a management plan, disease prevention and health promotion opportunities, identifying patient safety issues, the impact of the clinical presentation on the patient and family, and consideration of health equity factors. Analysis of the assessment scores indicated that the majority of students achieved the specified learning outcomes. The PCAP peer teaching activity was an acceptable and effective format for teaching about the management of chronic conditions in the community, and is adaptable to other teaching contexts. Students enjoyed teaching and being taught by their peers, and assessment results indicated that they developed their clinical knowledge as well as their teaching ability regarding chronic disease management. © 2014 John Wiley & Sons Ltd.

  19. Chronic kidney disease in patients at high risk of cardiovascular disease in the United Arab Emirates: A population-based study.

    PubMed

    Al-Shamsi, S; Regmi, D; Govender, R D

    2018-01-01

    Chronic kidney disease has become an increasingly significant clinical and public health issue, accounting for 1.1 million deaths worldwide. Information on the epidemiology of chronic kidney disease and associated risk factors is limited in the United Arab Emirates. Therefore, this study aimed to evaluate the incidence and causes of chronic kidney disease stages 3-5 in adult United Arab Emirates nationals with or at high risk of cardiovascular disease. This retrospective study included 491 adults with or at high risk of cardiovascular disease (diabetes mellitus or associated clinical disease) who attended outpatient clinics at a tertiary care hospital in Al-Ain, United Arab Emirates. Estimated glomerular filtration rate was assessed every 3 months from baseline to June 30, 2017. Chronic kidney disease stages 3-5 were defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for ≥ 3 months. Multivariable Cox's proportional hazards analysis was used to determine the independent risk factors associated with developing chronic kidney disease stages 3-5. The cumulative incidence of chronic kidney disease stages 3-5 over a 9-year period was 11.4% (95% confidence interval 8.6, 14.0). The incidence rate of these disease stages was 164.8 (95% confidence interval 121.6, 207.9) per 10,000 person-years. The independent risk factors for developing chronic kidney disease stages 3-5 were older age, history of coronary heart disease, history of diabetes mellitus, and history of smoking. These data may be useful to develop effective strategies to prevent chronic kidney disease development in high-risk United Arab Emirates nationals.

  20. PREDICTING CHRONIC TOXICITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA: CONCEPT AND LINEAR REGRESSION

    EPA Science Inventory

    A comprehensive approach to predicting chronic toxicity from acute.toxicity data was developed in which simultaneous consideration is given to concentration, degree of response, and time course of effect. onsistent endpoint (lethality) and degree of response (O%) were used to com...

  1. STATISTICAL APPROACH TO PREDICTING CHRONIC TOXICITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA

    EPA Science Inventory

    A comprehensive approach to predicting chronic toxicity from cute toxicity data was developed in which simultaneous onsideration is given to concentration, degree of response, and ime course of effect. onsistent endpoint (lethality) and degree of response (0 percent) were used to...

  2. Adult Children of Alcoholics and Chronic Career Indecision.

    ERIC Educational Resources Information Center

    Schumrum, Tiparat; Hartman, Bruce W.

    1988-01-01

    Based on a path analytic model, examines how chronic career indecision may develop as a result of growing up in an alcohol-related dysfunctional family. Concludes that, to improve the effectiveness of career counseling, more attention must be paid to differential diagnosis and appropriate intervention plans for clients. (ABL)

  3. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    NASA Astrophysics Data System (ADS)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  4. Compartmental and temporal dynamics of chronic inflammation and airway remodelling in a chronic asthma mouse model.

    PubMed

    Alrifai, Mohammed; Marsh, Leigh M; Dicke, Tanja; Kılıç, Ayse; Conrad, Melanie L; Renz, Harald; Garn, Holger

    2014-01-01

    Allergic asthma is associated with chronic airway inflammation and progressive airway remodelling. However, the dynamics of the development of these features and their spontaneous and pharmacological reversibility are still poorly understood. We have therefore investigated the dynamics of airway remodelling and repair in an experimental asthma model and studied how pharmacological intervention affects these processes. Using BALB/c mice, the kinetics of chronic asthma progression and resolution were characterised in absence and presence of inhaled corticosteroid (ICS) treatment. Airway inflammation and remodelling was assessed by the analysis of bronchoalveolar and peribronichal inflammatory cell infiltrate, goblet cell hyperplasia, collagen deposition and smooth muscle thickening. Chronic allergen exposure resulted in early (goblet cell hyperplasia) and late remodelling (collagen deposition and smooth muscle thickening). After four weeks of allergen cessation eosinophilic inflammation, goblet cell hyperplasia and collagen deposition were resolved, full resolution of lymphocyte inflammation and smooth muscle thickening was only observed after eight weeks. ICS therapy when started before the full establishment of chronic asthma reduced the development of lung inflammation, decreased goblet cell hyperplasia and collagen deposition, but did not affect smooth muscle thickening. These effects of ICS on airway remodelling were maintained for a further four weeks even when therapy was discontinued. Utilising a chronic model of experimental asthma we have shown that repeated allergen exposure induces reversible airway remodelling and inflammation in mice. Therapeutic intervention with ICS was partially effective in inhibiting the transition from acute to chronic asthma by reducing airway inflammation and remodelling but was ineffective in preventing smooth muscle hypertrophy.

  5. Tanezumab in the treatment of chronic musculoskeletal conditions.

    PubMed

    Jayabalan, Prakash; Schnitzer, Thomas J

    2017-02-01

    The management of pain associated with chronic musculoskeletal conditions represents a significant challenge for the clinician. There remains a need for novel medications that have a significant analgesic benefit and are also safe and well tolerated. Both pre-clinical and clinical data have provided evidence of the role of nerve growth factor (NGF) in a multitude of pain eliciting conditions. Therefore, the development of monoclonal antibodies to NGF for chronic painful musculoskeletal conditions has generated interest. Areas covered: This manuscript is a review that examines both the pharmacological properties and clinical studies of tanezumab, the most widely studied antibody to NGF, for management of osteoarthritis (OA) and low back pain. In addition, the safety and tolerability profile and development history of tanezumab are also discussed. Expert opinion: Most studies provide strong support for the ability of tanezumab to provide clinically meaningful pain relief in individuals with these conditions, with longer-term studies suggesting durability of effect. The adverse event profile appears favorable, assuming the risk mitigation strategies are effective at reducing the incidence of joint-related side effects. Further data are being collected to define the optimal dose and dosing strategy in both OA and chronic low back pain.

  6. Differential development of tolerance to the functional and behavioral effects of repeated baclofen treatment in rats

    PubMed Central

    Beveridge, T.J.R.; Smith, H.R.; Porrino, L.J.

    2013-01-01

    Baclofen, a gamma-aminobutyric acid (GABA)B receptor agonist, has been used clinically to treat muscle spasticity, rigidity and pain. More recently, interest in the use of baclofen as an addiction medicine has grown, with promising preclinical cocaine and amphetamine data and demonstrated clinical benefit from alcohol and nicotine studies. Few preclinical investigations, however, have utilized chronic dosing of baclofen, which is important given that tolerance can occur to many of its effects. Thus the question of whether chronic treatment of baclofen maintains the efficacy of acute doses is imperative. The neural substrates that underlie the effects of baclofen, particularly those after chronic treatment, are also not known. In the present study, therefore, rats were treated with either a) vehicle, b) acute baclofen (5 mg/kg) or c) chronic baclofen (5 mg/kg, t.i.d. for 5 days). The effects of acute and chronic baclofen administration, compared to vehicle, were assessed using locomotor activity and changes in brain glucose metabolism (a measure of functional brain activity). Acute baclofen significantly reduced locomotor activity (horizontal and total distance traveled), while chronic baclofen failed to affect locomotor activity. Acute baclofen resulted in significantly lower rates of local cerebral glucose utilization throughout many areas of the brain, including the prefrontal cortex, caudate putamen, septum and hippocampus. The majority of these functional effects, with the exception of the caudate putamen and septum, were absent in animals chronically treated with baclofen. Despite the tolerance to the locomotor and functional effects of baclofen following repeated treatment, these persistent effects on functional activity in the caudate putamen and septum may provide insights into the way in which baclofen alters the reinforcing effects of abused substances such as cocaine, alcohol, and methamphetamine both in humans and animal models. PMID:23500188

  7. Effects of consumer-centered u-health service for the knowledge, skill, and attitude of the patients with chronic obstructive pulmonary disease.

    PubMed

    Kim, Jeongeun; Kim, Sukwha; Kim, Hee-Chan; Kim, Kyung-Hwan; Yang, Seok-Chul; Lee, Choon-Taek; Kong, Hyoun-Joong; Lee, Kyungsoon

    2012-12-01

    Through the use of ubiquitous health, or u-Health, services, medical information can be adapted and made accessible via computer and Internet to provide quality healthcare to anybody, any place, and any time. We developed and implemented u-Health services for patients with chronic obstructive pulmonary disease and studied their experiences with respect to their knowledge of chronic obstructive pulmonary disease and skill and attitude toward the u-Health devices. The u-Health services were composed of telemonitoring and teleconsultation supplemented with home visits. To determine its effectiveness, the u-Health service system was implemented for 2 years with 144 chronic obstructive pulmonary disease patients in a clinical experiment. The subjects were divided into three experimental groups, each provided with different services, compared before and after intervention, and among groups. The analysis of data gathered through the system suggested that u-Health services can support patients with chronic obstructive pulmonary disease, improve patients' knowledge about chronic obstructive pulmonary disease self-management, build u-Health device usage skills, and foster a positive attitude toward u-Health devices. The u-Health services for the chronic obstructive pulmonary disease patients were both feasible and effective from the patients' perspective.

  8. Point-of-Care Diagnostics in Low-Resource Settings and Their Impact on Care in the Age of the Noncommunicable and Chronic Disease Epidemic.

    PubMed

    Weigl, Bernhard H; Neogi, Tina; McGuire, Helen

    2014-06-01

    The emergence of point-of-care (POC) diagnostics specifically designed for low-resource settings coupled with the rapid increase in need for routine care of patients with chronic diseases should prompt reconsideration of how health care can be delivered most beneficially and cost-effectively in developing countries. Bolstering support for primary care to provide rapid and appropriate integrated acute and chronic care treatment may be a possible solution. POC diagnostics can empower local and primary care providers and enable them to make better clinical decisions. This article explores the opportunity for POC diagnostics to strengthen primary care and chronic disease diagnosis and management in a low-resource setting (LRS) to deliver appropriate, consistent, and integrated care. We analyze the requirements of resource-appropriate chronic disease care, the characteristics of POC diagnostics in LRS versus the developed world, the many roles of diagnostics in the care continuum in LRS, and the process and economics of developing LRS-compatible POC diagnostics. © 2013 Society for Laboratory Automation and Screening.

  9. Development of a Novel Simulation Reactor for Chronic Exposure to Atmospheric Particulate Matter

    NASA Astrophysics Data System (ADS)

    Ye, Jianhuai; Salehi, Sepehr; North, Michelle L.; Portelli, Anjelica M.; Chow, Chung-Wai; Chan, Arthur W. H.

    2017-02-01

    Epidemiological studies have shown that air pollution is associated with the morbidity and mortality from cardiopulmonary diseases. Currently, limited experimental models are available to evaluate the physiological and cellular pathways activated by chronic multi-pollutant exposures. This manuscript describes an atmospheric simulation reactor (ASR) that was developed to investigate the health effects of air pollutants by permitting controlled chronic in vivo exposure of mice to combined particulate and gaseous pollutants. BALB/c mice were exposed for 1 hr/day for 3 consecutive days to secondary organic aerosol (SOA, a common particulate air pollutant) at 10-150 μg/m3, SOA (30 μg/m3) + ozone (65 ppb) or SOA + ozone (65 ppb) + nitrogen dioxide (NO2; 100 ppb). Daily exposure to SOA alone led to increased airway hyperresponsiveness (AHR) to methacholine with increasing SOA concentrations. Multi-pollutant exposure with ozone and/or NO2 in conjunction with a sub-toxic concentration of SOA resulted in additive effects on AHR to methacholine. Inflammatory cell recruitment to the airways was not observed in any of the exposure conditions. The ASR developed in this study allows us to evaluate the chronic health effects of relevant multi-pollutant exposures at ‘real-life’ levels under controlled conditions and permits repeated-exposure studies.

  10. Effects of low-level chronic irradiation on the radiosensitivity of mammals: Modeling studies

    NASA Astrophysics Data System (ADS)

    Smirnova, O. A.

    Mathematical models of the major hematopoietic lines are used to study the modifying effects of low-level chronic preirradiation on radiosensitivity of mammals which resulted in their reduced radiosensitivity (acquired radioresistance) and elevated radiosensitivity (hypersensitivity) to the subsequent radiation exposure. These effects of preirradiation manifest themselves, respectively, in decreased and increased mortality of preirradiated experimental animals (mice) after challenge acute exposure in comparison with that for previously nonirradiated ones. Analysis of the modeling results reveals the biological mechanisms of these radioprotection and radiosensitization effects, and enables one to estimate the ranges of dose rate and duration of chronic preirradiation where these effects are realized. Juxtapositions of the modeling predictions with the relevant experimental data show their qualitative agreement. All this testifies to the importance of accounting the nonlinear effect of low-level chronic irradiation on radiosensitivity of the hematopoiesis system and organism as a whole, when the radiation risk for astronauts on long-term space missions is estimated. The developed models of hematopoiesis can be used, after appropriate identification, as a component of the mathematical tools for radiation risk assessment.

  11. A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions

    PubMed Central

    Ding, Cody; Zhang, Jingqiu; Yang, Dong

    2018-01-01

    In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions. PMID:29755394

  12. The healthy learner model for student chronic condition management--part I.

    PubMed

    Erickson, Cecelia DuPlessis; Splett, Patricia L; Mullett, Sara Stoltzfus; Heiman, Mary Bielski

    2006-12-01

    A significant number of children have chronic health conditions that interfere with normal activities, including school attendance and active participation in the learning process. Management of students' chronic conditions is complex and requires an integrated system. Models to improve chronic disease management have been developed for the medical system and public health. Programs that address specific chronic disease management or coordinate school health services have been implemented in schools. Lacking is a comprehensive, integrated model that links schools, students, parents, health care, and other community providers. The Healthy Learner Model for chronic condition management identifies seven elements for creating, implementing, and sustaining an efficient and effective, comprehensive community-based system for improving the management of chronic conditions for school children. It has provided the framework for successful chronic condition management in an urban school district and is proposed for replication in other districts and communities.

  13. Chorioamnionitis and chronic lung disease of prematurity: a path analysis of causality.

    PubMed

    Dessardo, Nada Sindičić; Mustać, Elvira; Dessardo, Sandro; Banac, Srđan; Peter, Branimir; Finderle, Aleksandar; Marić, Marinko; Haller, Herman

    2012-02-01

    Current evidence suggests that additional pathogenetic factors could play a role in the development of chronic lung disease of prematurity, other than mechanical ventilation and free radical injury. The introduction of the concept of "fetal inflammatory response syndrome" offers a new perspective on the pathogenesis of chronic lung disease of prematurity. New statistical approaches could be useful tools in evaluating causal relationships in the development of chronic morbidity in preterm infants. The aim of this study was to test a new statistical framework incorporating path analysis to evaluate causality between exposure to chorioamnionitis and fetal inflammatory response syndrome and the development of chronic lung disease of prematurity. We designed a prospective cohort study that included consecutively born premature infants less than 32 weeks of gestation whose placentas were collected for histological analysis. Histological chorioamnionitis, clinical data, and neonatal outcomes were related to chronic lung disease. Along with standard statistical methods, a path analysis was performed to test the relationship between histological chorioamnionitis, gestational age, mechanical ventilation, and development of chronic lung disease of prematurity. Among the newborns enrolled in the study, 69/189 (36%) had histological chorioamnionitis. Of those with histological chorioamnionitis, 28/69 (37%) were classified as having fetal inflammatory response syndrome, according to the presence of severe chorioamnionitis and funisitis. Histological chorioamnionitis was associated with a lower birth weight, shorter gestation, higher frequency of patent ductus arteriosus, greater use of surfactant, and higher frequency of chronic lung disease of prematurity. Severe chorioamnionitis and funisitis were significantly associated with lower birth weight, lower gestational age, lower Apgar score at 5 minutes, more frequent use of mechanical ventilatory support and surfactant, as well as higher frequency of patent ductus arteriosus and chronic lung disease. The results of the path analysis showed that fetal inflammatory response syndrome has a significant direct (0.66), indirect (0.11), and overall (0.77) effect on chronic lung disease. This study demonstrated a strong positive correlation between exposure of the fetus to a severe inflammatory response and the development of chronic lung disease of prematurity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  14. Patient-professional partnerships and chronic back pain self-management: a qualitative systematic review and synthesis.

    PubMed

    Fu, Yu; McNichol, Elaine; Marczewski, Kathryn; Closs, S José

    2016-05-01

    Chronic back pain is common, and its self-management may be a lifelong task for many patients. While health professionals can provide a service or support for pain, only patients can actually experience it. It is likely that optimum self-management of chronic back pain may only be achieved when patients and professionals develop effective partnerships which integrate their complementary knowledge and skills. However, at present, there is no evidence to explain how such partnerships can influence patients' self-management ability. This review aimed to explore the influence of patient-professional partnerships on patients' ability to self-manage chronic back pain, and to identify key factors within these partnerships that may influence self-management. A systematic review was undertaken, aiming to retrieve relevant studies using any research method. Five databases were searched for papers published between 1980 and 2014, including Cochrane Library, CINAHL, Medline, EMBASE and PsycINFO. Eligible studies were those reporting on patients being supported by professionals to self-manage chronic back pain; patients being actively involved for self-managing chronic back pain; and the influence of patient-professional partnerships on self-management of chronic back pain. Included studies were critically appraised for quality, and findings were extracted and analysed thematically. A total of 738 studies were screened, producing 10 studies for inclusion, all of which happened to use qualitative methods. Seven themes were identified: communication, mutual understanding, roles of health professionals, information delivery, patients' involvement, individualised care and healthcare service. These themes were developed into a model suggesting how factors within patient-professional partnerships influence self-management. Review findings suggest that a partnership between patients and professionals supports patients' self-management ability, and effective communication is a fundamental factor underpinning their partnerships in care. It also calls for the development of individualised healthcare services offering self-referral or telephone consultation to patients with chronic conditions. © 2015 John Wiley & Sons Ltd.

  15. Chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring of the striatum.

    PubMed

    Taylor, S B; Anglin, J M; Paode, P R; Riggert, A G; Olive, M F; Conrad, C D

    2014-11-07

    Chronic stress is an established risk factor in the development of addiction. Addiction is characterized by a progressive transition from casual drug use to habitual and compulsive drug use. The ability of chronic stress to facilitate the transition to addiction may be mediated by increased engagement of the neurocircuitries underlying habitual behavior and addiction. In the present study, striatal morphology was evaluated after 2 weeks of chronic variable stress in male Sprague-Dawley rats. Dendritic complexity of medium spiny neurons was visualized and quantified with Golgi staining in the dorsolateral and dorsomedial striatum, as well as in the nucleus accumbens core and shell. In separate cohorts, the effects of chronic stress on habitual behavior and the acute locomotor response to methamphetamine were also assessed. Chronic stress resulted in increased dendritic complexity in the dorsolateral striatum and nucleus accumbens core, regions implicated in habitual behavior and addiction, while decreased complexity was found in the nucleus accumbens shell, a region critical for the initial rewarding effects of drugs of abuse. Chronic stress did not affect dendritic complexity in the dorsomedial striatum. A parallel shift toward habitual learning strategies following chronic stress was also identified. There was an initial reduction in acute locomotor response to methamphetamine, but no lasting effect as a result of chronic stress exposure. These findings suggest that chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring in the striatum. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  16. Longevity factor klotho and chronic psychological stress

    PubMed Central

    Prather, A A; Epel, E S; Arenander, J; Broestl, L; Garay, B I; Wang, D; Dubal, D B

    2015-01-01

    Chronic psychological stress is associated with accelerated aging and premature morbidity and mortality; however, the biology linking chronic psychological stress and its maladaptive effects remains largely unknown. Klotho is a pleiotropic hormone that regulates the aging process and promotes better brain and body health. Whether klotho is linked to psychosocial stress or its negative impact in humans has not been investigated. To address this gap, we recruited 178 healthy women who were either chronically high-stress maternal caregivers for a child with autism spectrum disorder (n=90) or low-stress control mothers of a typically developing child (n=88). We found that women under high chronic stress displayed significantly lower levels of the longevity hormone klotho compared with low-stress controls (t(176)=2.92, P=0.004; d=0.44), and the decrease among those under high stress was age-dependent. In addition, high-stress caregivers who reported more depressive symptoms displayed even lower klotho levels compared with low-stress participants. These findings provide the first evidence that klotho levels are sensitive to psychosocial stressors and raise the possibility that klotho may serve as a novel biological link connecting stress, depression and risk for accelerated disease development. Furthermore, these findings have important implications for understanding the plasticity of the aging process and may represent a therapeutic target for mitigating the deleterious effects of chronic psychological stress on health and well-being. PMID:26080320

  17. Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

    PubMed

    Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

    2013-11-15

    Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

  18. Spinal Ceramide and Neuronal Apoptosis in Morphine Antinociceptive Tolerance

    PubMed Central

    Bryant, Leesa; Doyle, Tim; Chen, Zhoumo; Cuzzocrea, Salvatore; Masini, Emanuela; Vinci, M. Cristina; Esposito, Emanuela; Mazzon, Emanuela; Petrusca, Daniela Nicoleta; Petrache, Irina; Salvemini, Daniela

    2009-01-01

    Opiates, like morphine, are the most effective analgesics for treating acute and chronic severe pain, but their use is limited by the development of analgesic tolerance and hypersensitivity to innocuous and noxious stimuli. Because opioids are a mainstay of pain management, restoring their efficacy has great clinical importance. We have recently demonstrated that spinal ceramide, a sphingolipid signaling molecule plays a central role in the development of morphine antinociceptive tolerance. We now report that ceramide up-regulation in dorsal horn tissues in response to chronic morphine administration is associated with significant neuronal apoptosis. Inhibition of ceramide biosynthesis attenuated both the increase in neuronal apoptosis and the development of antinociceptive tolerance. These findings indicate that spinal ceramide upregulation is a key pro-apoptotic event that occurs upstream of the development of morphine antinociceptive tolerance and support the rationale for development of inhibitors of ceramide biosynthesis as adjuncts to opiates for the management of chronic pain. PMID:19631718

  19. [Influence of smoking and industrial air pollutants on respiratory health of nickel industry workers].

    PubMed

    Shilov, V V; Siurin, S A

    2015-01-01

    Studies covered respiratory health of 1530 workers of nickel industry, among which were 796 (52.0%) smokers. Findings are that tobacco smoke combined with nickel industry hazards cause potentized negative effects in respiratory organs, with earlier and more frequent chronic bronchitis. For isolated influence of these factors, chronic bronchitis risk is higher from exposure to tobacco smoke vs. occupational hazards (OR = 2.48; DI 1.49-4.13). Chronic obstructive lung disease development in nickel industry workers is caused by smoking. Industrial air pollutants appeared to have no potentizing effect on COLD formation, as well as on toxic pneumosclerosis formation.

  20. Acute and chronic toxicity of buprofezin on Daphnia magna and the recovery evaluation.

    PubMed

    Liu, Yong; Qi, Suzhen; Zhang, Wen; Li, Xuefeng; Qiu, Lihong; Wang, Chengju

    2012-11-01

    The toxic effects of buprofezin on Daphnia magna after both chronic and acute exposures were evaluated according to OECD guidelines. A 48-h acute exposure of buprofezin resulted in daphnid immobility at an EC(50) of 0.44 mg/L. In a 14 days chronic exposure of buprofezin (0, 0.025, 0.05, 0.10 and 0.15 mg/L), the development and reproduction of daphnids were all significantly affected and the body length was more sensitive than other observed parameters. However, the adverse effects of buprofezin on parental daphnids can be passed on to their offspring and cannot be recovered in a short time.

  1. Hydrogen Treatment Protects Mice Against Chronic Pancreatitis by Restoring Regulatory T Cells Loss.

    PubMed

    Chen, Luguang; Ma, Chao; Bian, Yun; Li, Jing; Wang, Tiegong; Su, Li; Lu, Jianping

    2017-01-01

    Chronic pancreatitis is an inflammatory disease of the pancreas characterized by progressive tissue destruction and fibrogenesis. The development of chronic pancreatitis is associated with immune cell dysregulation. Currently, the specific and effective treatment of chronic pancreatitis remains absent. By using an L-arginine induced chronic pancreatitis mouse model, we tested the therapeutic potential of hydrogen, a strong hydroxyl radicals scavenger, in the chronic pancreatitis model. Tissue inflammation, damage and fibrosis were analyzed on HE, TUNEL, MPO, and sirius staining. Pancreas levels of MDA content, SOD activity, TNF-α , IL-10 cytokine expression and serum amylase and lipase activity were determined by ELISA and absorbance assay. Apoptosis, T cells subtype proportion and intracellular level of reactive oxygen species (ROS) were analyzed by flow cytometry. Tregs adoptive transfer and CD25 neutralization were used to validate the role of Tregs in chronic pancreatitis. We found that hydrogen treatment significantly improved multiple symptoms of chronic pancreatitis. The number of Tregs was reduced in chronic pancreatitis mice, while hydrogen treatment restored the Treg loss by L-arginine administrations. Depletion of Tregs abolished the protective effect of hydrogen treatment in chronic pancreatitis. In vitro study showed that hydrogen blocked ROS generation in Tregs and promoted Tregs survival. Hydrogen treatment showed reliable benefits in controlling the severity of chronic pancreatitis. Our study supported that hydrogen could be used as a novel treatment in chronic pancreatitis patient in the future. © 2017 The Author(s). Published by S. Karger AG, Basel.

  2. Chronic morbidities after traumatic brain injury: an update for the advanced practice nurse.

    PubMed

    Bay, Esther H; Chartier, Kattlynn S

    2014-06-01

    Emerging data suggest that traumatic brain injury (TBI) is a disease process with considerable long-range morbidities requiring lifelong monitoring and treatment. Multiple chronic morbidities develop across the life span after TBI, including mental health disorders, headaches, seizures, and neuroendocrine imbalances as well as chronic diseases. Still, there has been limited focus on effective guides and strategies for helping persons with TBI meet their chronic health needs as they live with the consequences of TBI. The advanced practice nurse is well positioned to participate collaboratively in practices that promote health screening and chronic disease management after TBI to ameliorate distress and enhance quality of life as persons with TBI live with lifelong consequences.

  3. Stress and obesity/metabolic syndrome in childhood and adolescence.

    PubMed

    Pervanidou, Panagiota; Chrousos, George P

    2011-09-01

    Chronic distress contributes to the development of obesity and comorbid states. Stress is the disturbance of the complex dynamic equilibrium that all organisms must maintain, and is associated with activation of the Stress system comprising of the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system functions in a baseline circadian fashion and interacts with other systems of the organism to regulate a variety of behavioral, endocrine, metabolic, immune and cardiovascular functions. The experience of perceived or real uncontrollable intense and/or chronic stress (distress) may lead to several psychopathologic conditions, including anxiety, depressive and psychosomatic disorders, substance abuse, obesity and the metabolic syndrome, and osteoporosis, as well as impaired reproductive and immune functions. Developing children and adolescents are particularly vulnerable to the effects of chronic stress. Both behavioral and biological pathways are involved in the connection between chronic stress and obesity in adults and children. Emotional "comfort" eating, lack of sleep, impulsive behaviours and selection of specific foods often characterize stressed individuals. In addition to specific behaviours, dysregulation of the stress system through increased secretion of cortisol and catecholamines, especially in the evening hours, and in concert with concurrently elevated insulin concentrations, leads to development of central obesity, insulin resistance and the metabolic syndrome. In children, chronic alterations in cortisol secretion may have additional effects on cognitive and emotional development, timing of puberty and final stature. Obese children and adolescents are frequently entangled in a vicious cycle between distress, impairing self-image and distorted self-image, maintaining and worsening distress.

  4. Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

    PubMed

    Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

    2010-08-01

    Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

  5. Effect of Levodopa on Reward and Impulsivity in a Rat Model of Parkinson’s Disease

    PubMed Central

    Carvalho, Miguel M.; Campos, Filipa L.; Marques, Mariana; Soares-Cunha, Carina; Kokras, Nikolaos; Dalla, Christina; Leite-Almeida, Hugo; Sousa, Nuno; Salgado, António J.

    2017-01-01

    The use of dopamine replacement therapies (DRT) in the treatment of Parkinson’s disease (PD) can lead to the development of dopamine dysregulation syndrome (DDS) and impulse control disorders (ICD), behavioral disturbances characterized by compulsive DRT self-medication and development of impulsive behaviors. However, the mechanisms behind these disturbances are poorly understood. In animal models of PD, the assessment of the rewarding properties of levodopa (LD), one of the most common drugs used in PD, has produced conflicting results, and its ability to promote increased impulsivity is still understudied. Moreover, it is unclear whether acute and chronic LD therapy differently affects reward and impulsivity. In this study we aimed at assessing, in an animal model of PD with bilateral mesostriatal and mesocorticolimbic degeneration, the behavioral effects of LD therapy regarding reward and impulsivity. Animals with either sham or 6-hydroxydopamine (6-OHDA)-induced bilateral lesions in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were exposed to acute and chronic LD treatment. We used the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of LD, whereas impulsive behavior was measured with the variable delay-to-signal (VDS) task. Correlation analyses between behavioral measurements of reward or impulsivity and lesion extent in SNc/VTA were performed to pinpoint possible anatomical links of LD-induced behavioral changes. We show that LD, particularly when administered chronically, caused the development of impulsive-like behaviors in 6-OHDA-lesioned animals in the VDS. However, neither acute or chronic LD administration had rewarding effects in 6-OHDA-lesioned animals in the CPP. Our results show that in a bilateral rat model of PD, LD leads to the development of impulsive behaviors, strengthening the association between DRT and DDS/ICD in PD. PMID:28848409

  6. Development and implementation of an integrated chronic disease model in South Africa: lessons in the management of change through improving the quality of clinical practice

    PubMed Central

    Asmall, Shaidah

    2015-01-01

    Background South Africa is facing a complex burden of disease arising from a combination of chronic infectious illness and non-communicable diseases. As the burden of chronic diseases (communicable and non-communicable) increases, providing affordable and effective care to the increasing numbers of chronic patients will be an immense challenge. Methods The framework recommended by the Medical Research Council of the United Kingdom for the development and evaluation of complex health interventions was used to conceptualise the intervention. The breakthrough series was utilised for the implementation process. These two frameworks were embedded within the clinical practice improvement model that served as the overarching framework for the development and implementation of the model. Results The Chronic Care Model was ideally suited to improve the facility component and patient experience; however, the deficiencies in other aspects of the health system building blocks necessitated a hybrid model. An integrated chronic disease management model using a health systems approach was initiated across 42 primary health care facilities. The interventions were implemented in a phased approach using learning sessions and action periods to introduce the planned and targeted changes. Conclusion The implementation of the integrated chronic disease management model is feasible at primary care in South Africa provided that systemic challenges and change management are addressed during the implementation process. PMID:26528101

  7. Development and implementation of an integrated chronic disease model in South Africa: lessons in the management of change through improving the quality of clinical practice.

    PubMed

    Mahomed, Ozayr Haroon; Asmall, Shaidah

    2015-01-01

    South Africa is facing a complex burden of disease arising from a combination of chronic infectious illness and non-communicable diseases. As the burden of chronic diseases (communicable and non-communicable) increases, providing affordable and effective care to the increasing numbers of chronic patients will be an immense challenge. The framework recommended by the Medical Research Council of the United Kingdom for the development and evaluation of complex health interventions was used to conceptualise the intervention. The breakthrough series was utilised for the implementation process. These two frameworks were embedded within the clinical practice improvement model that served as the overarching framework for the development and implementation of the model. The Chronic Care Model was ideally suited to improve the facility component and patient experience; however, the deficiencies in other aspects of the health system building blocks necessitated a hybrid model. An integrated chronic disease management model using a health systems approach was initiated across 42 primary health care facilities. The interventions were implemented in a phased approach using learning sessions and action periods to introduce the planned and targeted changes. The implementation of the integrated chronic disease management model is feasible at primary care in South Africa provided that systemic challenges and change management are addressed during the implementation process.

  8. Mechanism of Chronic Pain in Rodent Brain Imaging

    NASA Astrophysics Data System (ADS)

    Chang, Pei-Ching

    Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

  9. Effects of Shilajit on the development of tolerance to morphine in mice.

    PubMed

    Tiwari, P; Ramarao, P; Ghosal, S

    2001-03-01

    Effects of concomitant administration of Processed Shilajit (PS, 0.1 and 1 mg/kg, i.p.), in Swiss mice were evaluated on the development of tolerance to morphine induced analgesia in the hot plate test. Chronic administration of morphine (10 mg/kg, i.p., b.i.d.) to mice over a duration of 10 days resulted in the development of tolerance to the analgesic effect of morphine. Concomitant administration of PS with morphine, from day 6 to day 10, resulted in a significant inhibition of the development of tolerance to morphine (10 mg/kg, i.p.) induced analgesia. Processed Shilajit per se, in the doses used, did not elicit any significant analgesia in mice; nor did the chronic concomitant administration of Processed Shilajit alter the morphine-induced analgesia. These findings with Processed Shilajit indicate its potential as a prospective modifier of analgesic tolerance to morphine. Copyright 2001 John Wiley & Sons, Ltd.

  10. Providing Effective Early Intervention Vocational Rehabilitation at the Community Level

    ERIC Educational Resources Information Center

    Allaire, Saralynn J.; Niu, Jingbo; Zhu, Yanyan; Brett, Belle

    2011-01-01

    The purpose of this study was to evaluate the translation of positive research findings about a job retention intervention for persons with chronic illnesses to rehabilitation practice. A program to provide the intervention was developed and marketed in the community. Fifty-seven consumers with chronic illnesses received the intervention provided…

  11. Associations between Academic Achievement and Psychosocial Variables in Adolescents with Cystic Fibrosis

    ERIC Educational Resources Information Center

    Grieve, Adam J.; Tluczek, Audrey; Racine-Gilles, Caroline N.; Laxova, Anita; Albers, Craig A.; Farrell, Philip M.

    2011-01-01

    Background: Cystic fibrosis (CF) is a chronic genetic disease that leads to the accumulation of thick mucus in multiple organ systems, leading to chronic lung infection and affecting the body's ability to absorb nutrients necessary for growth and development. This cross-sectional, correlational study examined the potential effects of CF on…

  12. THE ROLE OF GENETIC SUSCEPTIBILITY IN EXPERIMENTAL INDUCTION CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND PARTICULATE MATTER (PM) HEALTH EFFECTS.

    EPA Science Inventory

    Human COPD represents the 4th common cause of mortality worldwide and is characterized by presence of chronic bronchitis/inflammation and emphysema. The primary cause is cigarette smoking, as nearly all COPD patients are smokers. However, only about 10% of smokers develop this di...

  13. Rehabilitation Counselor Preparation to Work with LGBTQ Persons Living with Chronic Illness/Disability: A Qualitative Content Analysis

    ERIC Educational Resources Information Center

    Dispenza, Franco; Elston, Nikki C.; Huffstead, Mary E.; Suttles, Mackenzie G.; Golubovic, Nedeljko

    2017-01-01

    Purpose: To identify meaningful educative experiences that contributed to the development of rehabilitation counselors' abilities to provide effective rehabilitation counseling services to lesbian, gay, bisexual, transgender, and queer (LGBTQ) persons living with chronic illness/disabilities (CID). Method: This was a secondary analysis of a larger…

  14. Anhedonia but not passive floating is an indicator of depressive-like behavior in two chronic stress paradigms.

    PubMed

    Stepanichev, Mikhail Yu; Tishkina, Anna O; Novikova, Margarita R; Levshina, Irina P; Freiman, Sofiya V; Onufriev, Mikhail V; Levchenko, Olga A; Lazareva, Natalia A; Gulyaeva, Natalia V

    2016-01-01

    Depression is the most common form of mental disability in the world. Depressive episodes may be precipitated by severe acute stressful events or by mild chronic stressors. Studies on the mechanisms of depression require both appropriate experimental models (most of them based on the exposure of animals to chronic stressors), and appropriate tests for assessment of depressive states. In this study male Wistar rats were exposed to two different chronic stress paradigms: an eight-week chronic unpredictable mild stress or a two-week combined chronic stress. The behavioral effects of stress were evaluated using sucrose preference, forced swim and open field tests. After the exposure to chronic unpredictable mild stress, anhedonia was developed, activity in the open field increased, while no changes in the duration of passive floating could be detected. After chronic combined stress, anhedonia was also evident, whereas behavior in the open field and forced swim test did not change. The levels of corticosterone in the blood and brain structures involved in stress-response did not differ from control in both experiments. The absence of significant changes in corticosterone levels and passive floating may be indicative of the adaptation of animals to chronic stress. Anhedonia appears to be a more sensitive indicator of depressive-like behavioral effects of chronic stress as compared to behavior in the forced swim or open field tests.

  15. Anxiogenic-like effects of chronic nicotine exposure in zebrafish.

    PubMed

    Stewart, Adam Michael; Grossman, Leah; Collier, Adam D; Echevarria, David J; Kalueff, Allan V

    2015-12-01

    Nicotine is one of the most widely used and abused legal drugs. Although its pharmacological profile has been extensively investigated in humans and rodents, nicotine CNS action remains poorly understood. The importance of finding evolutionarily conserved signaling pathways, and the need to apply high-throughput in vivo screens for CNS drug discovery, necessitate novel efficient experimental models for nicotine research. Zebrafish (Danio rerio) are rapidly emerging as an excellent organism for studying drug abuse, neuropharmacology and toxicology and have recently been applied to testing nicotine. Anxiolytic, rewarding and memory-modulating effects of acute nicotine treatment in zebrafish are consistently reported in the literature. However, while nicotine abuse is more relevant to long-term exposure models, little is known about chronic effects of nicotine on zebrafish behavior. In the present study, chronic 4-day exposure to 1-2mg/L nicotine mildly increased adult zebrafish shoaling but did not alter baseline cortisol levels. We also found that chronic exposure to nicotine evokes robust anxiogenic behavioral responses in zebrafish tested in the novel tank test paradigm. Generally paralleling clinical and rodent data on anxiogenic effects of chronic nicotine, our study supports the developing utility of zebrafish for nicotine research. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Psychometric evaluation of a new instrument to measure disease self-management of the early stage chronic kidney disease patients.

    PubMed

    Lin, Chiu-Chu; Wu, Chia-Chen; Wu, Li-Min; Chen, Hsing-Mei; Chang, Shu-Chen

    2013-04-01

    This study aims to develop a valid and reliable chronic kidney disease self-management instrument (CKD-SM) for assessing early stage chronic kidney disease patients' self-management behaviours. Enhancing early stage chronic kidney disease patients' self-management plays a key role in delaying the progression of chronic kidney disease. Healthcare provider understanding of early stage chronic kidney disease patients' self-management behaviours can help develop effective interventions. A valid and reliable instrument for measuring chronic kidney disease patients' self-management behaviours is needed. A cross-sectional descriptive study collected data for principal components analysis with oblique rotation. Mandarin- or Taiwanese-speaking adults with chronic kidney disease (n=252) from two medical centres and one regional hospital in Southern Taiwan completed the CKD-SM. Construct validity was evaluated by exploratory factor analysis. Internal consistency and test-retest reliability were estimated by Cronbach's alpha and Pearson correlation coefficients. Four factors were extracted and labelled self-integration, problem-solving, seeking social support and adherence to recommended regimen. The four factors accounted for 60.51% of the total variance. Each factor showed acceptable internal reliability with Cronbach's alpha from 0.77-0.92. The test-retest correlations for the CKD-SM was 0.72. The psychometric quality of the CKD-SM instrument was satisfactory. Research to conduct a confirmatory factor analysis to further validate this new instrument's construct validity is recommended. The CKD-SM instrument is useful for clinicians who wish to identify the problems with self-management among chronic kidney disease patients early. Self-management assessment will be helpful to develop intervention tailored to the needs of the chronic kidney disease population. © 2013 Blackwell Publishing Ltd.

  17. Framework to assess the effects of using patient-reported outcome measures in chronic care management.

    PubMed

    Santana, Maria-Jose; Feeny, David

    2014-06-01

    The inclusion of patient-reported outcome measures (PROMs) in the routine clinical care of chronically ill patients has the potential to add valuable information about the impact of the disease and its treatment and promotes effective patient self-management in which patients become more active participants in their own care. PROMs provide clinicians with timely information on patients' symptoms as well as functional and emotional status. PROMs are a useful tool for enhancing patient-clinician communication. We develop a conceptual framework describing the potential effects of the use of PROMs in chronic care management. The framework summarizes insights from the methods for evaluating the clinical effectiveness and methods for the health technology assessment of diagnostic technologies and results from the relevant studies. The framework describes potential effects, from proximal to distal, including communication (patient-clinician, patient-relative, clinician-clinician, and clinician-relative), engaging patients in shared clinical decision making, patient management (clinician management and patient self-management), and patient outcomes. Important potential effects also include enhancement in patient activation as well as improvements in clinician and patient satisfaction, and patient adherence to recommended treatment. Previous frameworks have described patient-physician communication, patient satisfaction, and health outcomes. Our framework adds unique domains, including patient engagement, patient activation, shared clinical decision making, and patient self-management. The framework can be used as a tool to guide the development of interventions to improve chronic care management through the use of PROMs.

  18. Effect of Bacopasides on acquisition and expression of morphine tolerance.

    PubMed

    Rauf, Khalid; Subhan, Fazal; Abbas, Muzaffar; Badshah, Amir; Ullah, Ihsan; Ullah, Sami

    2011-07-15

    Opioids are extensively used for the management of both chronic malignant and non malignant pains. One major serious limitation associated with chronic use of opioids is the development of tolerance to its analgesic effect. The effect of Bacopa monnieri, a renowned ayurvedic medicine for acquisition and expression of morphine tolerance in mice, was investigated. Bacopa monnieri, n-Butanol fraction was analyzed on High performance liquid chromatography (HPLC), for Bacopaside A major components i.e. Bacoside A(3), Bacopaside ll and Bacosaponin C. Antinociceptive effect of n-Butanol extract of Bacopa monnieri (n Bt-ext BM) (5, 10 and 15 mg/kg) was assessed on hot plate. Effect of different doses of n Bt-ext BM on morphine antinociception was also assessed. n Bt-ext BM was also screened for development of tolerance to antinociceptive effect of Bacopa monnieri by administering 15 mg/kg n Bt-ext BM for seven days. Tolerance to morphine analgesia was induced in mice by administering intraperitoneally (I.P.) 20 mg/kg morphine twice daily for five days. Acute and Chronic administration of 5, 10 and 15 mg/kg n Bt-ext BM significantly reduced both expression and development of tolerance to morphine analgesia in mice. Additionally, Bacopa monnieri was found to enhance antinociceptive effect of morphine in intolerant animals. However, no tolerance to Bacopa monnieri antinociceptive effect was observed in seven days treatment schedule. These findings indicate effectiveness of Bacopa monnieri for management of morphine tolerance. Copyright © 2011 Elsevier GmbH. All rights reserved.

  19. Evidence-Based mHealth Chronic Disease Mobile App Intervention Design: Development of a Framework.

    PubMed

    Wilhide Iii, Calvin C; Peeples, Malinda M; Anthony Kouyaté, Robin C

    2016-02-16

    Mobile technology offers new capabilities that can help to drive important aspects of chronic disease management at both an individual and population level, including the ability to deliver real-time interventions that can be connected to a health care team. A framework that supports both development and evaluation is needed to understand the aspects of mHealth that work for specific diseases, populations, and in the achievement of specific outcomes in real-world settings. This framework should incorporate design structure and process, which are important to translate clinical and behavioral evidence, user interface, experience design and technical capabilities into scalable, replicable, and evidence-based mobile health (mHealth) solutions to drive outcomes. The purpose of this paper is to discuss the identification and development of an app intervention design framework, and its subsequent refinement through development of various types of mHealth apps for chronic disease. The process of developing the framework was conducted between June 2012 and June 2014. Informed by clinical guidelines, standards of care, clinical practice recommendations, evidence-based research, best practices, and translated by subject matter experts, a framework for mobile app design was developed and the refinement of the framework across seven chronic disease states and three different product types is described. The result was the development of the Chronic Disease mHealth App Intervention Design Framework. This framework allowed for the integration of clinical and behavioral evidence for intervention and feature design. The application to different diseases and implementation models guided the design of mHealth solutions for varying levels of chronic disease management. The framework and its design elements enable replicable product development for mHealth apps and may provide a foundation for the digital health industry to systematically expand mobile health interventions and validate their effectiveness across multiple implementation settings and chronic diseases.

  20. Evidence-Based mHealth Chronic Disease Mobile App Intervention Design: Development of a Framework

    PubMed Central

    Peeples, Malinda M; Anthony Kouyaté, Robin C

    2016-01-01

    Background Mobile technology offers new capabilities that can help to drive important aspects of chronic disease management at both an individual and population level, including the ability to deliver real-time interventions that can be connected to a health care team. A framework that supports both development and evaluation is needed to understand the aspects of mHealth that work for specific diseases, populations, and in the achievement of specific outcomes in real-world settings. This framework should incorporate design structure and process, which are important to translate clinical and behavioral evidence, user interface, experience design and technical capabilities into scalable, replicable, and evidence-based mobile health (mHealth) solutions to drive outcomes. Objective The purpose of this paper is to discuss the identification and development of an app intervention design framework, and its subsequent refinement through development of various types of mHealth apps for chronic disease. Methods The process of developing the framework was conducted between June 2012 and June 2014. Informed by clinical guidelines, standards of care, clinical practice recommendations, evidence-based research, best practices, and translated by subject matter experts, a framework for mobile app design was developed and the refinement of the framework across seven chronic disease states and three different product types is described. Results The result was the development of the Chronic Disease mHealth App Intervention Design Framework. This framework allowed for the integration of clinical and behavioral evidence for intervention and feature design. The application to different diseases and implementation models guided the design of mHealth solutions for varying levels of chronic disease management. Conclusions The framework and its design elements enable replicable product development for mHealth apps and may provide a foundation for the digital health industry to systematically expand mobile health interventions and validate their effectiveness across multiple implementation settings and chronic diseases. PMID:26883135

  1. Divorce and Childhood Chronic Illness: A Grounded Theory of Trust, Gender, and Third-Party Care Providers.

    PubMed

    Russell, Luke T; Coleman, Marilyn; Ganong, Lawrence H; Gayer, Debra

    2016-05-01

    Divorced parents face distinct challenges in providing care for chronically ill children. Children's residence in two households necessitates the development of family-specific strategies to ensure coparents' supervision of regimen adherence and the management of children's health care. Utilizing a risk and resilience perspective, a grounded theory study was conducted with 14 divorced parents of children with chronic illnesses. The importance of trust, gender, and relationships with third-party care providers emerged as key themes related to the development of effective coparenting relationships for maintaining children's health. Divorced parents were best able to support the management of their children's chronic conditions when care providers operated as neutral third parties and intermediaries. Collaborative family care may require health care practitioners to avoid being drawn into contentious inter-parental conflicts. © The Author(s) 2016.

  2. Development of a Guided Internet-based Psycho-education Intervention Using Cognitive Behavioral Therapy and Self-Management for Individuals with Chronic Pain.

    PubMed

    Perry, Jennifer; VanDenKerkhof, Elizabeth G; Wilson, Rosemary; Tripp, Dean A

    2017-04-01

    Evidence-based chronic pain treatment includes nonpharmacologic therapies. When addressing barriers to treatment, there is a need to deliver these therapies in a way that is accessible to all individuals who may benefit. To develop a guided Internet-based intervention for individuals with chronic pain, program content and sequence of evidence-based treatments for chronic pain, traditionally delivered via in-person sessions, were identified to be adapted for Internet delivery. With consideration to historical barriers to treatment, and through use of a concept map, therapeutic components and educational material were situated, in an ordered sequence, into six modules. An Internet-based chronic pain intervention was constructed to improve access to evidence-based chronic pain therapies. Research using this intervention, in the form of a pilot study for intervention refinement, was conducted, and a large-scale study to assess effectiveness is necessary prior to implementation. As clients may face barriers to multimodal treatment for chronic pain, nurses could introduce components of education, cognitive behavioral therapy and self-management to clients and prepare them for the "work" of managing chronic pain, through use of this Internet-based intervention. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  3. Chronic Pain in Children and Adolescents: Diagnosis and Treatment of Primary Pain Disorders in Head, Abdomen, Muscles and Joints.

    PubMed

    Friedrichsdorf, Stefan J; Giordano, James; Desai Dakoji, Kavita; Warmuth, Andrew; Daughtry, Cyndee; Schulz, Craig A

    2016-12-10

    Primary pain disorders (formerly "functional pain syndromes") are common, under-diagnosed and under-treated in children and teenagers. This manuscript reviews key aspects which support understanding the development of pediatric chronic pain, points to the current pediatric chronic pain terminology, addresses effective treatment strategies, and discusses the evidence-based use of pharmacology. Common symptoms of an underlying pain vulnerability present in the three most common chronic pain disorders in pediatrics: primary headaches, centrally mediated abdominal pain syndromes, and/or chronic/recurrent musculoskeletal and joint pain. A significant number of children with repeated acute nociceptive pain episodes develop chronic pain in addition to or as a result of their underlying medical condition "chronic-on-acute pain." We provide description of the structure and process of our interdisciplinary, rehabilitative pain clinic in Minneapolis, Minnesota, USA with accompanying data in the treatment of chronic pain symptoms that persist beyond the expected time of healing. An interdisciplinary approach combining (1) rehabilitation; (2) integrative medicine/active mind-body techniques; (3) psychology; and (4) normalizing daily school attendance, sports, social life and sleep will be presented. As a result of restored function, pain improves and commonly resolves. Opioids are not indicated for primary pain disorders, and other medications, with few exceptions, are usually not first-line therapy.

  4. International recognition of the Chronic Otitis Media Questionnaire 12.

    PubMed

    Kosyakov, S I; Minavnina, J V; Phillips, J S; Yung, M W

    2017-06-01

    The Chronic Otitis Media Questionnaire 12 was developed initially in the UK to assess patient-reported health-related quality of life associated with chronic otitis media. This study aimed to determine whether this tool is applicable to the Russian population, which has a materially different healthcare system. A total of 108 patients with different forms of chronic otitis media completed the Russian Chronic Otitis Media Questionnaire 12. The average Russian Chronic Otitis Media Questionnaire 12 score was 19.4 (standard deviation = 8.3). The internal consistency of the Russian Chronic Otitis Media Questionnaire 12 was high, with a Cronbach's alpha value of 0.860. The Russian version of the Chronic Otitis Media Questionnaire 12 was found to be a reliable tool for the assessment of health-related quality of life in patients with chronic otitis media. This sets the scene for international collaboration, using this tool to assess the effectiveness of surgical treatments even amongst countries with different healthcare systems.

  5. Effect of accreditation on the quality of chronic disease management: a comparative observational study.

    PubMed

    van Doorn-Klomberg, Arna L; Braspenning, Jozé C C; Wolters, René J; Bouma, Margriet; Wensing, Michel

    2014-11-04

    Practice accreditation is widely used to assess and improve quality of healthcare providers. Little is known about its effectiveness, particularly in primary care. In this study we examined the effect of accreditation on quality of care regarding diabetes, chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD). A comparative observational study with two cohorts was performed. We included 138 Dutch family practices that participated in the national accreditation program for primary care. A first cohort of 69 practices was measured at start and completion of a 3-year accreditation program. A second cohort of 69 practices was included and measured simultaneously with the final measurement of the first cohort. In separate multilevel regression analyses, we compared both within-group changes in the first cohort and between-groups differences at follow-up (first cohort) and start (second cohort). Outcome measures consisted of 24 systematically developed indicators of quality of care in targeted chronic diseases. In the within-group comparison, we found improvements on 6 indicators related to diabetes (feet examination, cholesterol measurement, lipid lowering medication prescription) and COPD (spirometry performance, stop smoking advice). In the between-groups comparison we found that first cohort practices performed better on 4 indicators related to diabetes (cholesterol outcome) and CVD (blood pressure outcome, smoke status registration, glucose measurement). Improvements of the quality of primary care for patients with chronic diseases were found, but few could be attributed to the accreditation program. Further development of accreditation is needed to enhance its effectiveness on chronic disease management.

  6. Chronic radiation-induced dermatitis: challenges and solutions.

    PubMed

    Spałek, Mateusz

    2016-01-01

    Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients' quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF). RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and radiomics that allow scientists and clinicians to select patients who are at risk of the development of chronic radiation dermatitis. Novel treatment methods and clinical trials are strongly needed to provide more efficacious therapies.

  7. Chronic low back pain: a mini-review on pharmacological management and pathophysiological insights from clinical and pre-clinical data.

    PubMed

    Park, Thomas S W; Kuo, Andy; Smith, Maree T

    2018-05-12

    Globally, low back pain (LBP) is one of the most common health problems affecting humans. The lifetime prevalence of non-specific LBP is approximately 84%, with the chronic prevalence at about 23%. Chronic LBP in humans is defined as LBP that persists for more than 12 weeks without a significant pain improvement. Although there are numerous evidence-based guidelines on the management of acute LBP, this is not the case for chronic LBP, which is regarded as particularly difficult to treat. Research aimed at discovering new drug treatments for alleviation of chronic mechanical LBP is lacking due to the paucity of knowledge on the pathobiology of this condition, despite its high morbidity in the affected adult population. For a debilitating condition such as chronic LBP, it is necessary to assess the sustained effects of pharmacotherapy of various agents spanning months to years. Although many rodent models of mechanical LBP have been developed to mimic the human condition, some of the major shortcomings of many of these models are (1) the presence of a concurrent neuropathic component that develops secondary to posterior intervertebral disc puncture, (2) severe model phenotype, and/or (3) use of behavioural endpoints that have yet to be validated for pain. Hence, there is a great, unmet need for research aimed at discovering new biological targets in rodent models of chronic mechanical LBP for use in drug discovery programs as a means to potentially produce new highly effective and well-tolerated analgesic agents to improve relief of chronic LBP. On a cautionary note, it must be borne in mind that because humans and rats display orthograde and pronograde postures, respectively, the different mechanical forces on their spines add to the difficulty in translation of promising rodent data to humans.

  8. Chronic oedema: its prevalence, effects and management.

    PubMed

    Cooper, Garry

    2016-10-01

    Ageing affects not only individuals but also society. It occurs throughout the western world. The ageing process may lead to the development of conditions, such as chronic oedema, as well as comorbidities such as osteoarthritis. These comorbidities can make the management of chronic oedema even more difficult. This is an especially important consideration when tailoring individualised care plans, such as exercise, as conditions such as rheumatoid arthritis can limit patients' ability to manage their oedema. Despite challenges, education can improve patient outcomes when evidence-based practice is used.

  9. Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction.

    PubMed

    Bombas, A; Stein-Oakley, A N; Baxter, K; Thomson, N M; Jablonski, P

    1999-01-01

    Non-allogeneic factors such as increased nephron "workload" may contribute to chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, "tolerised" by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8% lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage.

  10. Mycophenolate mofetil combined with systemic corticosteroids prevents progression to chronic recurrent inflammation and development of 'sunset glow fundus' in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada disease.

    PubMed

    Abu El-Asrar, Ahmed M; Dosari, Mona; Hemachandran, Suhail; Gikandi, Priscilla W; Al-Muammar, Abdulrahman

    2017-02-01

    To evaluate the effectiveness and safety of mycophenolate mofetil (MMF) as first-line therapy combined with systemic corticosteroids in initial-onset acute uveitis associated with Vogt-Koyanagi-Harada (VKH) disease. This prospective study included 38 patients (76 eyes). The main outcome measures were final visual acuity, corticosteroid-sparing effect, progression to chronic recurrent granulomatous uveitis and development of complications, particularly 'sunset glow fundus'. The mean follow-up period was 37.0 ± 29.3 (range 9-120 months). Visual acuity of 20/20 was achieved by 93.4% of the eyes. Corticosteroid-sparing effect was achieved in all patients. The mean interval between starting treatment and tapering to 10 mg or less daily was 3.8 ± 1.3 months (range 3-7 months). Twenty-two patients (57.9%) discontinued treatment without relapse of inflammation. The mean time observed off of treatment was 28.1 ± 19.6 months (range 1-60 months). None of the eyes progressed to chronic recurrent granulomatous uveitis. The ocular complications encountered were glaucoma in two eyes (2.6%) and cataract in five eyes (6.6%). None of the eyes developed 'sunset glow fundus', and none of the patients developed any systemic adverse events associated with the treatment. Use of MMF as first-line therapy combined with systemic corticosteroids in patients with initial-onset acute VKH disease prevents progression to chronic recurrent granulomatous inflammation and development of 'sunset glow fundus'. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.

    PubMed

    Yarnitsky, David; Crispel, Yonathan; Eisenberg, Elon; Granovsky, Yelena; Ben-Nun, Alon; Sprecher, Elliot; Best, Lael-Anson; Granot, Michal

    2008-08-15

    Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.

  12. Effect of leaving chronic oral foci untreated on infectious complications during intensive chemotherapy

    PubMed Central

    Schuurhuis, J M; Span, L F R; Stokman, M A; van Winkelhoff, A J; Vissink, A; Spijkervet, F K L

    2016-01-01

    Background: Leukaemic patients receiving intensive chemotherapy and patients undergoing autologous stem-cell transplantation (ASCT) are routinely screened for oral foci of infection to reduce infectious complications that could occur during therapy. In this prospective study we assessed the effect of leaving chronic oral foci of infection untreated on the development of infectious complications in intensively treated haematological patients. Methods: We included and prospectively evaluated all intensively treated leukaemic patients and patients undergoing ASCT who were referred to our medical centre between September 2012 and May 2014, and who matched the inclusion/exclusion criteria. Acute oral foci of infection were removed before chemotherapy or ASCT, whereas chronic oral foci were left untreated. Results: In total 28 leukaemic and 35 ASCT patients were included. Acute oral foci of infection were found in 2 leukaemic (7%) and 2 ASCT patients (6%), and chronic oral foci of infection in 24 leukaemic (86%) and 22 ASCT patients (63%). Positive blood cultures with microorganisms potentially originating from the oral cavity occurred in 7 patients during treatment, but were uneventful on development of infectious complications. Conclusions: Our prospective study supports the hypothesis that chronic oral foci of infection can be left untreated as this does not increase infectious complications during intensive chemotherapy. PMID:27002936

  13. Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives.

    PubMed

    Boobis, Alan; Cerniglia, Carl; Chicoine, Alan; Fattori, Vittorio; Lipp, Markus; Reuss, Rainer; Verger, Philippe; Tritscher, Angelika

    2017-11-01

    The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.

  14. CHRONIC PERCHLORATE EXPOSURE CAUSES MORPHOLOGICAL ABNORMALITIES IN DEVELOPING STICKLEBACK

    PubMed Central

    Bernhardt, Richard R.; Von Hippel, Frank A.; O’Hara, Todd M.

    2011-01-01

    Few studies have examined the effects of chronic perchlorate exposure during growth and development, and fewer still have analyzed the effects of perchlorate over multiple generations. We describe morphological and developmental characteristics for threespine stickleback (Gasterosteus aculeatus) that were spawned and raised to sexual maturity in perchlorate-treated water (G1,2003) and for their offspring (G2,2004) that were not directly treated with perchlorate. The G1,2003 displayed a variety of abnormalities, including impaired formation of calcified traits, slower growth rates, aberrant sexual development, poor survivorship, and reduced pigmentation that allowed internal organs to be visible. Yet these conditions were absent when the offspring of contaminated fish (G2,2004) were raised in untreated water, suggesting a lack of transgenerational effects and that surviving populations may be able to recover following remediation of perchlorate-contaminated sites PMID:21465539

  15. Cannabinoid receptor 2 agonist attenuates pain related behavior in rats with chronic alcohol/high fat diet induced pancreatitis.

    PubMed

    Zhang, Liping; Kline, Robert H; McNearney, Terry A; Johnson, Michael P; Westlund, Karin N

    2014-11-17

    Chronic Pancreatitis (CP) is a complex and multifactorial syndrome. Many contributing factors result in development of dysfunctional pain in a significant number of patients. Drugs developed to treat a variety of pain states fall short of providing effective analgesia for patients with chronic pancreatitis, often providing minimal to partial pain relief over time with significant side effects. Recently, availability of selective pharmacological tools has enabled great advances in our knowledge of the role of the cannabinoid receptors in pathophysiology. In particular, cannabinoid receptor 2 (CB2) has emerged as an attractive target for management of chronic pain, as demonstrated in several studies with inflammatory and neuropathic preclinical pain models. In this study, the analgesic efficacy of a novel, highly selective CB2 receptor agonist, LY3038404 HCl, is investigated in a chronic pancreatitis pain model, induced with an alcohol/high fat (AHF) diet. Rats fed the AHF diet developed visceral pain-like behaviors detectable by week 3 and reached a maximum at week 5 that persists as long as the diet is maintained. Rats with AHF induced chronic pancreatitis were treated with LY3038404 HCl (10 mg/kg, orally, twice a day for 9 days). The treated animals demonstrated significantly alleviated pain related behaviors after 3 days of dosing, including increased paw withdrawal thresholds (PWT), prolonged abdominal withdrawal latencies (ABWL), and decreased nocifensive responses to noxious 44°C hotplate stimuli. Terminal histological analysis of pancreatic tissue sections from the AHF chronic pancreatitis animals demonstrated extensive injury, including a global pancreatic gland degeneration (cellular atrophy), vacuolization (fat deposition), and fibrosis. After the LY3038404 HCl treatment, pancreatic tissue was significantly protected from severe damage and fibrosis. LY3038404 HCl affected neither open field exploratory behaviors nor dark/light box preferences as measures of higher brain and motor functions. LY3038404 HCl, a potent CB2 receptor agonist, possesses tissue protective and analgesic properties without effects on higher brain function. Thus, activation of CB2 receptors is suggested as a potential therapeutic target for visceral inflammation and pain management.

  16. Development of an ear cap in chronic suppurative otitis media using additive manufacturing and TRIZ.

    PubMed

    Mawale, Mahesh B; Kuthe, Abhaykumar; Mawale, Anupama M; Dahake, Sandeep W

    2018-06-01

    The prevalence rate of chronic suppurative otitis media is high and its treatment continues to be a challenge for the otorhinolaryngologists. Due to middle ear infection, there may be pain, hearing loss and spontaneous rupture of the eardrum which results in perforation. Infections can cause a hole in the eardrum as a side effect of otitis media. The patients suffering from ear perforation or having a hole in eardrum require preventing entry of water in the ear. This article describes the development of ear cap using additive manufacturing and TRIZ (a collaborative tool) to prevent the entry of water in the ear during chronic otitis media.

  17. Natural history of chronic hepatitis B virus infection.

    PubMed

    Busch, Katrin; Thimme, Robert

    2015-02-01

    Hepatitis B virus infection represents a major global health problem. Currently, there are more than 240 million chronically infected people worldwide. The development of chronic hepatitis B virus-mediated liver disease may lead to liver fibrosis, cirrhosis and eventually hepatocellular carcinoma. Recently, the discovery of the viral entry receptor sodium taurocholate cotransporting polypeptide has facilitated new approaches for a better understanding of viral physiopathology. Hopefully, these novel insights may give rise to the development of more effective antiviral therapy concepts during the next years. In this review, we will discuss the natural history of hepatitis B virus infection including the viral biology, the clinical course of infection and the role of the immune response.

  18. Systematic review of positive youth development programs for adolescents with chronic illness.

    PubMed

    Maslow, Gary R; Chung, Richard J

    2013-05-01

    The Positive Youth Development (PYD) framework has been successfully used to support at-risk youth. However, its effectiveness in fostering positive outcomes for adolescents with chronic illness has not been established. We performed a systematic review of PYD-consistent programs for adolescents with chronic illness. Data sources included PubMed, CINAHL, and PsychINFO. Guided by an analytic framework, we searched for studies of PYD-consistent programs serving adolescents and young adults aged 13 through 24 with chronic illness. References were screened iteratively with increasing depth until a focused cohort was obtained and reviewed in full. The authors separately reviewed the studies using structured analysis forms. Relevant study details were abstracted during the review process. Fifteen studies describing 14 programs were included in the analysis. Three comprehensive programs included all 3 core components of a PYD program, including opportunities for youth leadership, skill building, and sustained connections between youth and adults. Four programs were primarily mentoring programs, and 7 others focused on youth leadership. Programs served youth with a variety of chronic illnesses. The quality and type of evaluation varied considerably, with most reporting psychosocial outcomes but only a few including medical outcomes. The PYD-consistent programs identified in this review can serve as models for the development of youth development programs for adolescents with chronic illness. Additional study is needed to evaluate such programs rigorously with respect to both psychosocial and health-related outcomes. PYD-consistent programs have the potential to reach youth with chronic illness and promote positive adult outcomes broadly.

  19. New Directions in Chronic Disease Management.

    PubMed

    Kim, Hun Sung; Cho, Jae Hyoung; Yoon, Kun Ho

    2015-06-01

    A worldwide epidemic of chronic disease, and complications thereof, is underway, with no sign of abatement. Healthcare costs have increased tremendously, principally because of the need to treat chronic complications of non-communicable diseases including cardiovascular disease, blindness, end-stage renal disease, and amputation of extremities. Current healthcare systems fail to provide an appropriate quality of care to prevent the development of chronic complications without additional healthcare costs. A new paradigm for prevention and treatment of chronic disease and the complications thereof is urgently required. Several clinical studies have clearly shown that frequent communication between physicians and patients, based on electronic data transmission from medical devices, greatly assists in the management of chronic disease. However, for various reasons, these advantages have not translated effectively into real clinical practice. In the present review, we describe current relevant studies, and trends in the use of information technology for chronic disease management. We also discuss limitations and future directions.

  20. Analgesic effect of clobazam in chronic low-back pain but not in experimentally induced pain.

    PubMed

    Schliessbach, J; Vuilleumier, P H; Siegenthaler, A; Bütikofer, L; Limacher, A; Juni, P; Zeilhofer, H U; Arendt-Nielsen, L; Curatolo, M

    2017-09-01

    Chronic pain is frequently associated with hypersensitivity of the nervous system, and drugs that increase central inhibition are therefore a potentially effective treatment. Benzodiazepines are potent modulators of GABAergic neurotransmission and are known to exert antihyperalgesic effects in rodents, but translation into patients are lacking. This study investigates the effect of the benzodiazepine clobazam in chronic low-back pain in humans. The aim of this study is to explore the effect of GABA modulation on chronic low-back pain and on quantitative sensory tests. In this double-blind cross-over study, 49 patients with chronic low-back pain received a single oral dose of clobazam 20 mg or active placebo tolterodine 1 mg. Pain intensity on the 0-10 numeric rating scale and quantitative sensory tests were assessed during 2 h after drug intake. Pain intensity in the supine position was significantly reduced by clobazam compared to active placebo (60 min: 2.9 vs. 3.5, p = 0.008; 90 min: 2.7 vs. 3.3, p = 0.024; 120 min: 2.4 vs. 3.1, p = 0.005). Pain intensity in the sitting position was not significantly different between groups. No effects on quantitative sensory tests were observed. This study suggests that clobazam has an analgesic effect in patients with chronic low-back pain. Muscle relaxation or sedation may have contributed to the effect. Development of substances devoid of these side effects would offer the potential to further investigate the antihyperalgesic action of GABAergic compounds. Modulation of GABAergic pain-inhibitory pathways may be a potential future therapeutic target. © 2017 European Pain Federation - EFIC®.

  1. Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion.

    PubMed

    Qu, Jie; Zhou, Qiong; Du, Ying; Zhang, Wei; Bai, Miao; Zhang, Zhuo; Xi, Ye; Li, Zhuyi; Miao, Jianting

    2014-08-01

    Chronic cerebral hypoperfusion is a critical causative factor for the development of cognitive decline and dementia in the elderly, which involves many pathophysiological processes. Consequently, inhibition of several pathophysiological pathways is an attractive therapeutic strategy for this disorder. Rutin, a biologically active flavonoid, protects the brain against several insults through its antioxidant and anti-inflammatory properties, but its effect on cognitive deficits and brain damage caused by chronic cerebral hypoperfusion remains unknown. Here, we investigated the neuroprotective effect of rutin on cognitive impairments and the potential mechanisms underlying its action in rats with chronic cerebral hypoperfusion. We used Sprague-Dawley rats with permanent bilateral common carotid artery occlusion (BCCAO), a well-established model of chronic cerebral hypoperfusion. After rutin treatment for 12 weeks, the neuroprotective effect of rutin in rats was evaluated by behavioural tests, biochemical and histopathological analyses. BCCAO rats showed marked cognitive deficits, which were improved by rutin treatment. Moreover, BCCAO rats exhibited central cholinergic dysfunction, oxidative damage, inflammatory responses and neuronal damage in the cerebral cortex and hippocampus, compared with sham-operated rats. All these effects were significantly alleviated by treatment with rutin. Our results provide new insights into the pharmacological actions of rutin and suggest that rutin has multi-targeted therapeutical potential on cognitive deficits associated with conditions with chronic cerebral hypoperfusion such as vascular dementia and Alzheimer's disease. © 2014 The British Pharmacological Society.

  2. Efficacy of Boric Acid as a Treatment of Choice for Chronic Suppurative Otitis Media and Its Ototoxicity.

    PubMed

    Adriztina, Indri; Adenin, Linda Irwani; Lubis, Yuliani Mardiati

    2018-01-01

    Chronic suppurative otitis media (CSOM) is one of the most common chronic infectious diseases worldwide, especially affecting children. The patients or the parents of the affected children are often worried about the cost of medical visits, prescription medicines, or inconsistently effective medication. The complications of CSOM have been greatly reduced because of the development of antibiotics; however, the irrational use of antibiotics has led to the emergence of organisms resistant to the commonly used drugs. Owing to the increase in antibiotic resistance, the development of new treatments that will efficiently eradicate infectious microorganisms has become imperative. Boric acid solutions are effective in the treatment of CSOM because of their acidic effect. Various databases, such as the PubMed, The Cochrane Library, and SciELO, were searched for references related to the efficacy of boric acid in the treatment of mucosal CSOM, as well as its ototoxicity. The search revealed that boric acid is relatively effective in treating CSOM, especially at a high concentration. Boric acid in distilled water was found safe in animal studies. However, the ototoxicity of boric acid concentrations higher than 4% needs further evaluation, considering the effectivity of boric acid at high concentrations.

  3. Efficacy of Boric Acid as a Treatment of Choice for Chronic Suppurative Otitis Media and Its Ototoxicity

    PubMed Central

    Adenin, Linda Irwani; Lubis, Yuliani Mardiati

    2018-01-01

    Chronic suppurative otitis media (CSOM) is one of the most common chronic infectious diseases worldwide, especially affecting children. The patients or the parents of the affected children are often worried about the cost of medical visits, prescription medicines, or inconsistently effective medication. The complications of CSOM have been greatly reduced because of the development of antibiotics; however, the irrational use of antibiotics has led to the emergence of organisms resistant to the commonly used drugs. Owing to the increase in antibiotic resistance, the development of new treatments that will efficiently eradicate infectious microorganisms has become imperative. Boric acid solutions are effective in the treatment of CSOM because of their acidic effect. Various databases, such as the PubMed, The Cochrane Library, and SciELO, were searched for references related to the efficacy of boric acid in the treatment of mucosal CSOM, as well as its ototoxicity. The search revealed that boric acid is relatively effective in treating CSOM, especially at a high concentration. Boric acid in distilled water was found safe in animal studies. However, the ototoxicity of boric acid concentrations higher than 4% needs further evaluation, considering the effectivity of boric acid at high concentrations. PMID:29383205

  4. Computational Identification of Mechanistic Factors That Determine the Timing and Intensity of the Inflammatory Response

    PubMed Central

    Nagaraja, Sridevi; Reifman, Jaques; Mitrophanov, Alexander Y.

    2015-01-01

    Timely resolution of inflammation is critical for the restoration of homeostasis in injured or infected tissue. Chronic inflammation is often characterized by a persistent increase in the concentrations of inflammatory cells and molecular mediators, whose distinct amount and timing characteristics offer an opportunity to identify effective therapeutic regulatory targets. Here, we used our recently developed computational model of local inflammation to identify potential targets for molecular interventions and to investigate the effects of individual and combined inhibition of such targets. This was accomplished via the development and application of computational strategies involving the simulation and analysis of thousands of inflammatory scenarios. We found that modulation of macrophage influx and efflux is an effective potential strategy to regulate the amount of inflammatory cells and molecular mediators in both normal and chronic inflammatory scenarios. We identified three molecular mediators − tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and the chemokine CXCL8 − as potential molecular targets whose individual or combined inhibition may robustly regulate both the amount and timing properties of the kinetic trajectories for neutrophils and macrophages in chronic inflammation. Modulation of macrophage flux, as well as of the abundance of TNF-α, TGF-β, and CXCL8, may improve the resolution of chronic inflammation. PMID:26633296

  5. The Impact of Big Data on Chronic Disease Management.

    PubMed

    Bhardwaj, Niharika; Wodajo, Bezawit; Spano, Anthony; Neal, Symaron; Coustasse, Alberto

    Population health management and specifically chronic disease management depend on the ability of providers to prevent development of high-cost and high-risk conditions such as diabetes, heart failure, and chronic respiratory diseases and to control them. The advent of big data analytics has potential to empower health care providers to make timely and truly evidence-based informed decisions to provide more effective and personalized treatment while reducing the costs of this care to patients. The goal of this study was to identify real-world health care applications of big data analytics to determine its effectiveness in both patient outcomes and the relief of financial burdens. The methodology for this study was a literature review utilizing 49 articles. Evidence of big data analytics being largely beneficial in the areas of risk prediction, diagnostic accuracy and patient outcome improvement, hospital readmission reduction, treatment guidance, and cost reduction was noted. Initial applications of big data analytics have proved useful in various phases of chronic disease management and could help reduce the chronic disease burden.

  6. [Application of cryogenic stimulation in treatment of chronic wounds].

    PubMed

    Vinnik, Iu S; Karapetian, G E; Iakimov, S V; Sychev, A G

    2008-01-01

    The authors have studied alterations occurring both in the ultrastructure of the cell matrix and in the microcirculatory bed of the chronic wound after local exposure to cryoagent. The up-to-date effective methods including laser Doppler flowmetry were used followed by correct statistical processing of the data obtained. The cryogenic stimulation of the wound was shown to result in considerably improved perfusion of the microcirculatory bed, epithelization and remodeling of the scar. It allowed transformation of a chronic process into acute and thus led to considerably accelerated process of regeneration. The developed method of cryogenic treatment of the chronic wound was used in 35 patients, allowed quicker healing of the chronic wounds and made ambulatory treatment of the patients 3 weeks shorter.

  7. Development of a Conceptual Model for Smoking Cessation: Physical Activity, Neurocognition, and Executive Functioning

    ERIC Educational Resources Information Center

    Loprinzi, Paul D.; Herod, Skyla M.; Walker, Jerome F.; Cardinal, Bradley J.; Mahoney, Sara E.; Kane, Christy

    2015-01-01

    Purpose: Considerable research has shown adverse neurobiological effects of chronic alcohol use, including long-term and potentially permanent changes in the structure and function of the brain; however, much less is known about the neurobiological consequences of chronic smoking, as it has largely been ignored until recently. In this article, we…

  8. An integrated framework for the geographic surveillance of chronic disease

    PubMed Central

    2009-01-01

    Background Geographic public health surveillance is concerned with describing and disseminating geographic information about disease and other measures of health to policy makers and the public. While methodological developments in the geographical analysis of disease are numerous, few have been integrated into a framework that also considers the effects of case ascertainment bias on the effectiveness of chronic disease surveillance. Results We present a framework for the geographic surveillance of chronic disease that integrates methodological developments in the spatial statistical analysis and case ascertainment. The framework uses an hierarchical approach to organize and model health information derived from an administrative health data system, and importantly, supports the detection and analysis of case ascertainment bias in geographic data. We test the framework on asthmatic data from Alberta, Canada. We observe high prevalence in south-western Alberta, particularly among Aboriginal females. We also observe that persons likely mistaken for asthmatics tend to be distributed in a pattern similar to asthmatics, suggesting that there may be an underlying social vulnerability to a variety of respiratory illnesses, or the presence of a diagnostic practice style effect. Finally, we note that clustering of asthmatics tends to occur at small geographic scales, while clustering of persons mistaken for asthmatics tends to occur at larger geographic scales. Conclusion Routine and ongoing geographic surveillance of chronic diseases is critical to developing an understanding of underlying epidemiology, and is critical to informing policy makers and the public about the health of the population. PMID:19948046

  9. Functional and Histological Effects of Chronic Neural Electrode Implantation.

    PubMed

    Sahyouni, Ronald; Chang, David T; Moshtaghi, Omid; Mahmoodi, Amin; Djalilian, Hamid R; Lin, Harrison W

    2017-04-01

    Permanent injury to the cranial nerves can often result in a substantial reduction in quality of life. Novel and innovative interventions can help restore form and function in nerve paralysis, with bioelectric interfaces among the more promising of these approaches. The foreign body response is an important consideration for any bioelectric device as it influences the function and effectiveness of the implant. The purpose of this review is to describe tissue and functional effects of chronic neural implantation among the different categories of neural implants and highlight advances in peripheral and cranial nerve stimulation. Data Sources : PubMed, IEEE, and Web of Science literature search. Review Methods : A review of the current literature was conducted to examine functional and histologic effects of bioelectric interfaces for neural implants. Bioelectric devices can be characterized as intraneural, epineural, perineural, intranuclear, or cortical depending on their placement relative to nerves and neuronal cell bodies. Such devices include nerve-specific stimulators, neuroprosthetics, brainstem implants, and deep brain stimulators. Regardless of electrode location and interface type, acute and chronic histological, macroscopic and functional changes can occur as a result of both passive and active tissue responses to the bioelectric implant. A variety of chronically implantable electrodes have been developed to treat disorders of the peripheral and cranial nerves, to varying degrees of efficacy. Consideration and mitigation of detrimental effects at the neural interface with further optimization of functional nerve stimulation will facilitate the development of these technologies and translation to the clinic. 3.

  10. Linking the microbiota, chronic disease and the immune system

    PubMed Central

    Hand, Timothy W.; Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K.; Belkaid, Yasmine

    2016-01-01

    Chronic inflammatory diseases are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many chronic inflammatory diseases are associated with significant shifts in the microbiota towards inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites. This review discusses recent findings suggesting that shifts in the microbiota may contribute to chronic disease via effects on the immune system. PMID:27623245

  11. Addressing chronic operational issues at the W. M. Keck Observatory

    NASA Astrophysics Data System (ADS)

    Nordin, Tom; Matsuda, Richard

    2016-07-01

    The W. M. Keck Observatory (WMKO) has a good track record at addressing large critical faults which impact observing. Our performance tracking and correcting chronic minor faults has been mixed, yet this class of problems has a significant negative impact on scientific productivity and staff effectiveness. We have taken steps to address this shortcoming. This paper outlines the creation of a program to identify, categorize and rank these chronic operational issues, track them over time, and develop management options for their resolution. The success of the program at identifying these chronic operational issues and the advantages of dedicating observatory resources to this endeavor are presented.

  12. Pediatric Lung Transplantation.

    PubMed

    Sweet, Stuart C

    2017-06-01

    Pediatric lung transplant is a viable option for treatment of end-stage lung disease in children, with > 100 pediatric lung transplants reported to the Registry of the International Society of Heart and Lung Transplantation each year. Long-term success is limited by availability of donor organs, debilitation as a result of chronic disease, impaired mucus clearance resulting from both surgical and pharmacologic interventions, increased risk for infection resulting from immunosuppression, and most importantly late complications, such as chronic lung allograft dysfunction. Opportunities for investigation and innovation remain in all of these domains: (1) Ex vivo lung perfusion is a promising technology with the potential for increasing the lung donor pool, (2) evolving extracorporeal support strategies coupled with effective rehabilitation will effectively bridge critically ill patients to transplant, and most importantly, (3) research efforts intended to increase our understanding of the underlying mechanisms of chronic lung allograft dysfunction will ultimately lead to the development of effective therapies to prevent or treat the variety of chronic lung allograft dysfunction presentations. Copyright © 2017 by Daedalus Enterprises.

  13. Long-term effects of canine parvovirus infection in dogs.

    PubMed

    Kilian, Elena; Suchodolski, Jan S; Hartmann, Katrin; Mueller, Ralf S; Wess, Gerhard; Unterer, Stefan

    2018-01-01

    Canine parvovirus (CPV) is the most important viral cause of acute canine enteritis leading to severe damage of the intestinal barrier. It has been speculated that dogs might develop chronic disorders after surviving CPV infection. However, no studies regarding the long-term implications of CPV infection have been published to date. The aim of this study was to evaluate whether dogs that have survived CPV infection will have an increased risk for developing chronic gastroenteritis, atopic dermatitis, or cardiac disease. Dogs that had been treated at the Clinic of Small Animal Medicine, LMU Munich, for CPV infection for which a follow-up of at least 12 months was available, were included in the study. Owners completed a questionnaire on the presence of chronic gastrointestinal and cutaneous signs, cardiac disease, and other potential disorders. An identical questionnaire was sent to owners of matched control dogs during the same time period. Seventy-one questionnaires of dogs with CPV infection and 67 of control dogs were analyzed. Significantly more CPV-infected dogs (30/71) compared to control dogs (8/67) had developed chronic gastrointestinal signs later in their lives (P < 0.001). No significant differences were observed regarding skin diseases (P = 1), cardiac problems (P = 0.160), or any other diseases (P = 0.173) later in life. Results of this study suggest that dogs that survive CPV infection have a significantly higher risk (odds ratio = 5.33) for developing a chronic gastrointestinal disease. Further prospective studies to identify the trigger for the development of chronic diarrhoea and possible targeted treatment strategies are needed.

  14. Research needs for an improved primary care response to chronic non-communicable diseases in Africa.

    PubMed

    Maher, D; Sekajugo, J; Harries, A D; Grosskurth, H

    2010-02-01

    With non-communicable diseases (NCDs) projected to become leading causes of morbidity and mortality in developing countries, research is needed to improve the primary care response, especially in sub-Saharan Africa. This region has a particularly high double burden of communicable diseases and NCDs and the least resources for an effective response. There is a lack of good quality epidemiological data from diverse settings on chronic NCD burden in sub-Saharan Africa, and the approach to primary care of people with chronic NCDs is currently often unstructured. The main primary care research needs are therefore firstly, epidemiological research to document the burden of chronic NCDs, and secondly, health system research to deliver the structured, programmatic, public health approach that has been proposed for the primary care of people with chronic NCDs. Documentation of the burden and trends of chronic NCDs and associated risk factors in different settings and different population groups is needed to enable health system planning for an improved primary care response. Key research issues in implementing the programmatic framework for an improved primary care response are how to (i) integrate screening and prevention within health delivery; (ii) validate the use of standard diagnostic protocols for NCD case-finding among patients presenting to the local health facilities; (iii) improve the procurement and provision of standardised treatment and (iv) develop and implement a data collection system for standardised monitoring and evaluation of patient outcomes. Important research considerations include the following: selection of research sites and the particular NCDs targeted; research methodology; local research capacity; research collaborations; ethical issues; translating research findings into policy and practice and funding. Meeting the research needs for an improved health system response is crucial to deliver effective, affordable and equitable care for the millions of people with chronic NCDs in developing countries in Africa.

  15. Chronic carbon monoxide treatment attenuates development of obesity and remodels adipocytes in mice fed a high-fat diet.

    PubMed

    Hosick, P A; AlAmodi, A A; Storm, M V; Gousset, M U; Pruett, B E; Gray, W; Stout, J; Stec, D E

    2014-01-01

    Induction of heme oxygenase-1 (HO-1) has been demonstrated to result in chronic weight loss in several rodent models of obesity. However, the specific contribution of the HO metabolite, carbon monoxide (CO) to this response remains unknown. In this study, we determined the effect of chronic low level administration of a specific CO donor on the progression of obesity and its effects on metabolism and adipocyte biology in mice fed a high-fat diet. Experiments were performed on C57BL/6J mice fed a high-fat diet (60%) from 4 weeks until 30 weeks of age. Mice were administered either the CO donor, carbon monoxide releasing molecules (CORM)-A1 (5 mg kg(-1), intraperitoneally every other day) or the inactive form of the drug (iCORM-A1). Body weights were measured weekly and fasted blood glucose, insulin as well as body composition were measured every 6 weeks. Food intake, O2 consumption, CO2 production, activity and body heat production were measured at 28 weeks after start of the experimental protocol. Chronic CORM-A1 attenuated the development of high fat induced obesity from 18 weeks until the end of the study. Chronic CORM-A1 treatment in mice fed a high-fat diet resulted in significant decreases in fasted blood glucose, insulin and body fat and increased O2 consumption and heat production as compared with mice treated with iCORM-A1. Chronic CORM-A1 treatment also resulted in a significant decrease in adipocyte size and an increase in adipocyte number and in NRF-1, PGC-1α and UCP1 protein levels in epidydmal fat. Our results demonstrate that chronic CO treatment prevents the development of high-fat diet induced obesity via stimulation of metabolism and remodeling of adipocytes.

  16. Wound management with compression therapy and topical hemoglobin solution in a patient with Budd-Chiari Syndrome.

    PubMed

    Babadagi-Hardt, Zeynep; Engels, Peter; Kanya, Susanne

    2014-03-31

    Although the underlying primary cause of chronic wounds may vary, a common etiology of this is a hypoxic or ischemic status of the affected tissue of the lower extremities. In particular, for rare diseases associated with disturbed blood flow a correlation between cause and effect is often diagnosed inappropriately. As a consequence, chronic wounds may develop and persist for years. We present a case of a patient with chronic venous insufficiency due to an occlusion of the inferior caval vein. Initially, a Budd-Chiari syndrome was diagnosed which is a thrombotic obstruction of the hepatic venous outflow. In addition, the patient developed an obstruction of the inferior caval vein and subsequently a chronic venous insufficiency. As a consequence, chronic leg ulcers developed with a history of more than 7 years. Various wound care approaches were performed without success in wound closure. Finally, a combination of compression therapy and topical application of a hemoglobin solution successfully led to fast and persistent wound closure. Chronic ulcers of the lower limb such as venous leg ulcers, even for patients with rare disorders like Budd-Chiari syndrome, are associated with oxygen supply disturbances resulting in a hypoxic status of the affected tissue. Therefore, an adequate oxygen supply to chronic wounds plays a pivotal role in successful wound healing. Compression therapy in combination with enhancement of the local oxygen supply by topically applied hemoglobin showed marked improvement of wound healing in the presented patient.

  17. Development and validation of the Salzburg COPD-screening questionnaire (SCSQ): a questionnaire development and validation study.

    PubMed

    Weiss, Gertraud; Steinacher, Ina; Lamprecht, Bernd; Kaiser, Bernhard; Mikes, Romana; Sator, Lea; Hartl, Sylvia; Wagner, Helga; Studnicka, M

    2017-01-26

    Chronic obstructive pulmonary disease prevalence rates are still high. However, the majority of subjects are not diagnosed. Strategies have to be implemented to overcome the problem of under-diagnosis. Questionnaires could be used to pre-select subjects for spirometry and thereby help reducing under-diagnosis. We report a brief, simple, self-administrable and validated chronic obstructive pulmonary disease questionnaire to increase the pre-test probability for chronic obstructive pulmonary disease diagnosis in subjects undergoing confirmatory spirometry. In 2005, we completed the Austrian Burden of Obstructive Lung Disease-study in 1258 subjects aged >40 years. Post-bronchodilator spirometry was performed, and non-reversible airflow limitation defined by FEV 1 /FVC ratio below the lower limit of normal. Questions from the Salzburg chronic obstructive pulmonary disease screening-questionnaire were selected using a logistic regression model, and risk scores were based on regression-coefficients. A training sub-sample (n = 800) was used to create the score, and a test sub-sample (n = 458) was used to test it. In 2008, an external validation study was done, using the same protocol in 775 patients from primary care. The Salzburg chronic obstructive pulmonary disease screening questionnaire was composed of items related to "breathing problems", "wheeze", "cough", "limitation of physical activity", and "smoking". At the >=2 points cut-off of the Salzburg chronic obstructive pulmonary disease screening questionnaire, sensitivity was 69.1% [95%CI: 56.6%; 79.5%], specificity 60.0% [95%CI: 54.9%; 64.9%], the positive predictive value 23.2% [95%CI: 17.7%; 29.7%] and the negative predictive value 91.8% [95%CI: 87.5%; 95.7%] to detect post bronchodilator airflow limitation. The external validation study in primary care confirmed these findings. The Salzburg chronic obstructive pulmonary disease screening questionnaire was derived from the highly standardized Burden of Obstructive Lung Disease study. This validated and easy to use questionnaire can help to increase the efficiency of chronic obstructive pulmonary disease case-finding. QUESTIONNAIRE FOR PRE-SCREENING POTENTIAL SUFFERERS: Scientists in Austria have developed a brief, simple questionnaire to identify patients likely to have early-stage chronic lung disease. Chronic obstructive pulmonary disease (COPD) is notoriously difficult to diagnose, and the condition often causes irreversible lung damage before it is identified. Finding a simple, cost-effective method of pre-screening patients with suspected early-stage COPD could potentially improve treatment responses and limit the burden of extensive lung function ('spirometry') tests on health services. Gertraud Weiss at Paracelsus Medical University, Austria, and co-workers have developed and validated an easy-to-use, self-administered questionnaire that could prove effective for pre-screening patients. The team trialed the five-point Salzburg COPD-screening questionnaire on 1258 patients. Patients scoring 2 points or above on the questionnaire underwent spirometry tests. The questionnaire seems to provide a sensitive and cost-effective way of pre-selecting patients for spirometry referral.

  18. Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

    PubMed

    Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

    2011-06-01

    Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2). For mice that did not experience CVS, early social isolation resulted in greater ethanol intake compared with group-housed mice (Experiment 3). CVS subsequently resulted in a significant increase in ethanol intake in group-housed mice, but CVS failed to further increase ethanol intake in mice that experienced chronic social isolation early in life (Experiment 3). Overall, female mice consumed more ethanol than males, whether isolated (early or late) or group housed. These results indicate that early but not late social isolation can subsequently influence ethanol consumption in C57BL/6J mice. Thus, the developmental timing of chronic social isolation appears to be an important factor in defining later effects on ethanol self-administration behavior. In addition, experience with CVS early in life results in elevated ethanol intake later in adulthood. Taken together, these results emphasize the important role of early stress experiences that modulate later voluntary ethanol intake during adulthood. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Emerging topical onychomycosis therapies - quo vadis?

    PubMed

    Elkeeb, Rania; Hui, Xiaoying; Murthy, Narasimha; Maibach, Howard I

    2014-12-01

    Onychomycosis, a common chronic fungal infection affecting fingernails and toenails, globally may affect 10 - 30% of the population. This chronic disease is difficult to eradicate. The goal of developing a highly effective and safe topical treatment has not yet been reached as it depends on the type of onychomycosis and the variety of invaders. Topical drug delivery to the nail is highly desirable in treating nail disorders. However, efficacy of topical therapies is low due to their limited permeability across the nail plate. Advances have especially been made by the development of new therapeutic options including new drug entities, new formulations and reformulations. This overview updates emerging topical treatments for onychomycosis, research progress and future perspectives. Development of novel effective noninvasive topical therapy for treating onychomycosis and other nail diseases such as psoriasis is long overdue. Previously there was a lack of basic knowledge about nail and its barrier properties, but with the recent increased interest in this field both from industry and academia, we hope extensive research will continue in this field to bring about successful and safe treatments for such chronic diseases.

  20. LONG-TERM EFFECTS OF ADVERSE ENVIRONMENTS DURING DEVELOPMENT: EFFECTS ON ADULTHOOD IN RATS EXPOSED TO TOXICANTS OR UNDERNUTRITION IN UTERO.

    EPA Science Inventory

    Studies have shown correlations between in utero and early life environments and diseases later in life, including hypertension, coronary heart disease, diabetes, obesity, schizophrenia, early onset chronic renal failure, cancer and compromised repro-duction. Current development...

  1. Effectiveness of gratitude disposition promotion program on depression and quality of life of chronic schizophrenic patients.

    PubMed

    Jung, Miran; Han, Kuemsun

    2017-01-01

    Gratitude intervention is expectedly an effective intervention to reduce depression and improve the quality of life in schizophrenic patients, but there is a lack of literature on it. We attempted to develop and test the effectiveness of the gratitude disposition promotion program for chronic schizophrenic patients in Korea. Nonequivalent control group pre- and post-test design was used in two mental health centers located at Gyeonggi-do in South Korea. This paper was a quasi-experimental study and the participants who took part in the gratitude disposition promotion program were 17 of experimental group and 15 of control group. Gratitude disposition (the short gratitude, resentment, and appreciation test), depression (Beck Depression Inventory), and quality of life (developed by Kook) of chronic schizophrenic patients were measured before and after an intervention, as compared to the control. Chi-square test, Fisher's exact test, and t -test were performed for prehomogeneity testing for variables related to the general characteristics. Testing for the effectiveness of gratitude disposition promotion program and hypothesis testing for its effect on depression and quality of life were by ANCOVA and t -test, as verified to significance level of P < 0.05. The participants who received the gratitude disposition promotion program showed significant improvements in gratitude disposition ( F = 18.740, P < 0.0001) and in quality of life ( F = 9.800, P = 0.004), but no significant difference in depression ( F = 3.870, P = 0.059). The gratitude disposition promotion program was an effective clinical intervention program for enhancing gratitude disposition and quality of life of chronic schizophrenic patients in community.

  2. Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity

    PubMed Central

    Cao, Dianjun; Cao, Qian M.; Subramaniam, Sakthivel; Yugo, Danielle M.; Heffron, C. Lynn; Rogers, Adam J.; Kenney, Scott P.; Tian, Debin; Matzinger, Shannon R.; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

    2017-01-01

    Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ–specific CD4+ T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α–specific CD8+ T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E. PMID:28630341

  3. Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity.

    PubMed

    Cao, Dianjun; Cao, Qian M; Subramaniam, Sakthivel; Yugo, Danielle M; Heffron, C Lynn; Rogers, Adam J; Kenney, Scott P; Tian, Debin; Matzinger, Shannon R; Overend, Christopher; Catanzaro, Nicholas; LeRoith, Tanya; Wang, Heng; Piñeyro, Pablo; Lindstrom, Nicole; Clark-Deener, Sherrie; Yuan, Lijuan; Meng, Xiang-Jin

    2017-07-03

    Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection. During chronic infection, serum levels of the liver enzyme γ-glutamyl transferase and fecal virus shedding were significantly higher in immunocompromised HEV-infected pigs. To identify potential immune correlates of chronic infection, we determined serum levels of cytokines and cell-mediated immune responses in pigs. Results showed that HEV infection of immunocompromised pigs reduced the serum levels of Th1 cytokines IL-2 and IL-12, and Th2 cytokines IL-4 and IL-10, particularly during the acute phase of infection. Furthermore IFN-γ-specific CD4 + T-cell responses were reduced in immunocompromised pigs during the acute phase of infection, but TNF-α-specific CD8 + T-cell responses increased during the chronic phase of infection. Thus, active suppression of cell-mediated immune responses under immunocompromised conditions may facilitate the establishment of chronic HEV infection. This pig model will aid in delineating the mechanisms of chronic HEV infection and in developing effective therapeutics against chronic hepatitis E.

  4. A center for self-management of chronic illnesses in diverse groups.

    PubMed

    Inouye, Jillian; Boland, Mary G; Nigg, Claudio R; Sullivan, Kathleen; Leake, Anne; Mark, Debra; Albright, Cheryl L

    2011-01-01

    Prevention and successful treatment of chronic disease require a scientific understanding of the impacts and interactions of ethnicity, culture, and illness on self-management interventions. This article presents one approach to developing effective methods to address the needs of ethnic minorities living with chronic illnesses. Described is the University of Hawaii Center for Ohana Self-Management of Chronic Illnesses (COSMCI) located in the School of Nursing & Dental Hygiene and funded by the National Institute of Nursing Research (Award Number P20NR010671). The interdisciplinary center focuses on family and community self-management interventions in ethnically diverse populations with chronic illnesses. Areas discussed are: 1) the operational structure for creating an environment conducive to interdisciplinary ohana self-management chronic illness research in ethnically diverse populations; and 2) the development of sustainable interdisciplinary, biobehavioral research capacity. The COSMCI uses a social cognitive theory framework to guide the application of established self-management interventions to Asian and Pacific Island populations (API) through three conceptually linked research projects on HIV infection, type 2 diabetes, and chronic obstructive pulmonary disease. COSMI addresses the feasibility of sharing of lessons learned among the approaches taken. The interdisciplinary nature of COSMCI increases the potential success of the intervention efforts. Hawaii Medical Journal Copyright 2010.

  5. Developmental Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    PubMed Central

    Portugal, George S.; Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2012-01-01

    Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, such as changes in nicotinic acetylcholine receptor (nAChR) binding, CREB expression, and nicotine metabolism. Age-related differences existed in sensitivity to the effects of acute nicotine, chronic nicotine and nicotine withdrawal on contextual fear conditioning (no changes in cued fear conditioning were seen); younger mice were more sensitive to the acute effects and less sensitive to the effects of nicotine withdrawal 24 hours post treatment cessation. Developmental differences in nAChR binding were associated with the effects of nicotine withdrawal on contextual learning. Developmental differences in nicotine metabolism and CREB expression were also observed, but were not related to the effects of nicotine withdrawal on contextual learning 24 hours post treatment. Chronic nicotine exposure during pre-adolescence or adolescence, however, produced long-lasting impairments in contextual learning that were observed during adulthood, whereas adult chronic nicotine exposure did not. These developmental effects could be related to changes in CREB. Overall, there is a developmental shift in the effects of nicotine on hippocampus-dependent learning and developmental exposure to nicotine results in adult cognitive deficits; these changes in cognition may play an important role in the development and maintenance of nicotine addiction. PMID:22521799

  6. 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.

  7. Chronic Pain in Children and Adolescents: Diagnosis and Treatment of Primary Pain Disorders in Head, Abdomen, Muscles and Joints

    PubMed Central

    Friedrichsdorf, Stefan J.; Giordano, James; Desai Dakoji, Kavita; Warmuth, Andrew; Daughtry, Cyndee; Schulz, Craig A.

    2016-01-01

    Primary pain disorders (formerly “functional pain syndromes”) are common, under-diagnosed and under-treated in children and teenagers. This manuscript reviews key aspects which support understanding the development of pediatric chronic pain, points to the current pediatric chronic pain terminology, addresses effective treatment strategies, and discusses the evidence-based use of pharmacology. Common symptoms of an underlying pain vulnerability present in the three most common chronic pain disorders in pediatrics: primary headaches, centrally mediated abdominal pain syndromes, and/or chronic/recurrent musculoskeletal and joint pain. A significant number of children with repeated acute nociceptive pain episodes develop chronic pain in addition to or as a result of their underlying medical condition “chronic-on-acute pain.” We provide description of the structure and process of our interdisciplinary, rehabilitative pain clinic in Minneapolis, Minnesota, USA with accompanying data in the treatment of chronic pain symptoms that persist beyond the expected time of healing. An interdisciplinary approach combining (1) rehabilitation; (2) integrative medicine/active mind-body techniques; (3) psychology; and (4) normalizing daily school attendance, sports, social life and sleep will be presented. As a result of restored function, pain improves and commonly resolves. Opioids are not indicated for primary pain disorders, and other medications, with few exceptions, are usually not first-line therapy. PMID:27973405

  8. [Experimental validation of the efficacy of laser-magnetic therapy for chronic placental insufficiency].

    PubMed

    Ordzhonikidze, N V; Filimonov, V G; Klimenko, P A; Kondrikov, N I; Akin'shina, V S; Berlin, Iu V

    1994-01-01

    A new pathogenetically based non-medicamentous method for correction of uteroplacental bloodflow disturbances has been developed on the model of chronic placental insufficiency in rats. A single 5 min laser-magnetic exposure on day 21 of normal pregnancy resulted in a vasodilating effect with reduction of the peripheral resistance in the uterine horn vessels and with improvement of their blood supply. A new LAMA laser magneto-therapeutic device was employed. Daily 5 min sessions of laser magnetic therapy administered to rats with chronic placental insufficiency from pregnancy days 15-16 to 21 normalized uterine horn contractility and resulted in positive morphofunctional changes in the components of the uterine horns and placenta, being associated with a noticeable improvement of fetal functions. Hence, laser magnetic therapy may be regarded as an effective non-drug method for therapy of chronic placental insufficiency.

  9. [Latest advances in chronic pancreatitis].

    PubMed

    Domínguez Muñoz, J Enrique

    2015-09-01

    This article summarizes some of the recent and clinically relevant advances in chronic pancreatitis. These advances mainly concern the early diagnosis of the disease, the treatment of symptoms and complications, mainly pain and pancreatic exocrine insufficiency, and the diagnosis and therapy of autoimmune pancreatitis. The multimodal dynamic endoscopic ultrasound-guided secretin-stimulated evaluation of the pancreas provides relevant morphological and functional information for the diagnosis of chronic pancreatitis at early stages. Extracorporeal shock wave lithotripsy in patients with calcifying pancreatitis and endoscopic pancreatic stent placement are effective alternatives for pain therapy in patients with chronic pancreatitis. Presence of pancreatic exocrine insufficiency in patients with chronic pancreatitis is associated with a significantly increase of mortality rate. Despite that, pancreatic enzyme replacement therapy is not prescribed in the majority of patients with pancreatic exocrine insufficiency, or it is prescribed at a low dose. The newly developed and commercialized needles for endoscopic ultrasound-guided pancreatic biopsy are effective in retrieving appropriate tissue samples for the histological diagnosis of autoimmune pancreatitis. Maintenance therapy with azathioprine is effective and safe to prevent relapses in patients with autoimmune pancreatitis. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  10. Synergistic effects on dopamine cell death in a Drosophila model of chronic toxin exposure

    PubMed Central

    Martin, Ciara A.; Barajas, Angel; Lawless, George; Lawal, Hakeem O.; Assani, Khadij; Lumintang, Yosephine P.; Nunez, Vanessa; Krantz, David E.

    2014-01-01

    The neurodegenerative effects of Parkinson’s disease (PD) are marked by a selective loss of dopaminergic (DA) neurons. Epidemiological studies suggest that chronic exposure to the pesticide paraquat may increase the risk for PD and DA cell loss. However, combined exposure with additional fungicide(s) including maneb and/or ziram may be required for pathogenesis. To explore potential pathogenic mechanisms, we have developed a Drosophila model of chronic paraquat exposure. We find that while chronic paraquat exposure alone decreased organismal survival and motor function, combined chronic exposure to both paraquat and maneb was required for DA cell death in the fly. To initiate mechanistic studies of this interaction, we used additional genetic reagents to target the ubiquitin proteasome system, implicated in some rare familial forms of PD and the toxic effects of ziram. Genetic inhibition of E1 ubiquitin ligase, but not the proteasome itself, increased DA cell death in combination with maneb but not paraquat. These studies establish a model for long-term exposure to multiple pesticides, and support the idea that pesticide interactions relevant to PD may involve inhibition of protein ubiquitination. PMID:25160001

  11. Policy Guidelines for Effective Inclusion and Reintegration of People with Chronic Diseases in the Workplace: National and European Perspectives.

    PubMed

    Vlachou, Anastasia; Stavroussi, Panayiota; Roka, Olga; Vasilou, Evdokia; Papadimitriou, Dimitra; Scaratti, Chiara; Kadyrbaeva, Asel; Fheodoroff, Klemens; Brecelj, Valentina; Svestkova, Olga; Tobiasz-Adamczyk, Beata; Finnvold, Jon Erik; Gruber, Sonja; Leonardi, Matilde

    2018-03-11

    The increasing prevalence of chronic diseases among the European working age population, as well as the implications for the individual and societal level, underline the need for policy guidelines targeting the effective inclusion of persons with chronic diseases in the workplace. The aim of the present paper was to explore the perspectives of European and National-level stakeholders on existing strategies for work re-integration of persons with chronic diseases, and to provide policy guidelines. A highly-structured interview protocol was distributed to 58 National level stakeholders (policy makers, professionals and employers) from seven European countries. Additionally, 20 European organizations concerned with health-related issues and employment completed an online survey. The findings reveal that employment-related challenges remain largely unaddressed. Both national and European stakeholders considered the existing legislative frameworks inadequate and appraised the co-ordination for the implementation of employment re-integration policies as ineffective. Policies targeting at work re-integration of persons with chronic diseases at European and national level should focus on consistent cooperation among all key stakeholders, awareness raising to staff and management, dissemination of effective strategies, developing research and evaluation standards and establishing monitoring systems on inclusive labour markets.

  12. Dipeptidyl peptidase-4: A key player in chronic liver disease

    PubMed Central

    Itou, Minoru; Kawaguchi, Takumi; Taniguchi, Eitaro; Sata, Michio

    2013-01-01

    Dipeptidyl peptidase-4 (DPP-4) is a membrane-associated peptidase, also known as CD26. DPP-4 has widespread organ distribution throughout the body and exerts pleiotropic effects via its peptidase activity. A representative target peptide is glucagon-like peptide-1, and inactivation of glucagon-like peptide-1 results in the development of glucose intolerance/diabetes mellitus and hepatic steatosis. In addition to its peptidase activity, DPP-4 is known to be associated with immune stimulation, binding to and degradation of extracellular matrix, resistance to anti-cancer agents, and lipid accumulation. The liver expresses DPP-4 to a high degree, and recent accumulating data suggest that DPP-4 is involved in the development of various chronic liver diseases such as hepatitis C virus infection, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Furthermore, DPP-4 occurs in hepatic stem cells and plays a crucial role in hepatic regeneration. In this review, we described the tissue distribution and various biological effects of DPP-4. Then, we discussed the impact of DPP-4 in chronic liver disease and the possible therapeutic effects of a DPP-4 inhibitor. PMID:23613622

  13. Using Visual Scene Displays as Communication Support Options for People with Chronic, Severe Aphasia: A Summary of AAC Research and Future Research Directions.

    PubMed

    Beukelman, David R; Hux, Karen; Dietz, Aimee; McKelvey, Miechelle; Weissling, Kristy

    2015-01-01

    Research about the effectiveness of communicative supports and advances in photographic technology has prompted changes in the way speech-language pathologists design and implement interventions for people with aphasia. The purpose of this paper is to describe the use of photographic images as a basis for developing communication supports for people with chronic aphasia secondary to sudden-onset events due to cerebrovascular accidents (strokes). Topics include the evolution of AAC-based supports as they relate to people with aphasia, the development and key features of visual scene displays (VSDs), and future directions concerning the incorporation of photographs into communication supports for people with chronic and severe aphasia.

  14. Interventions for the prediction and management of chronic postsurgical pain after total knee replacement: systematic review of randomised controlled trials

    PubMed Central

    Beswick, Andrew D; Wylde, Vikki; Gooberman-Hill, Rachael

    2015-01-01

    Objectives Total knee replacement can be a successful operation for pain relief. However, 10–34% of patients experience chronic postsurgical pain. Our aim was to synthesise evidence on the effectiveness of applying predictive models to guide preventive treatment, and for interventions in the management of chronic pain after total knee replacement. Setting We conducted a systematic review of randomised controlled trials using appropriate search strategies in the Cochrane Library, MEDLINE and EMBASE from inception to October 2014. No language restrictions were applied. Participants Adult patients receiving total knee replacement. Interventions Predictive models to guide treatment for prevention of chronic pain. Interventions for management of chronic pain. Primary and secondary outcome measures Reporting of specific outcomes was not an eligibility criterion but we sought outcomes relating to pain severity. Results No studies evaluated the effectiveness of predictive models in guiding treatment and improving outcomes after total knee replacement. One study evaluated an intervention for the management of chronic pain. The trial evaluated the use of a botulinum toxin A injection with antinociceptive and anticholinergic activity in 49 patients with chronic postsurgical pain after knee replacement. A single injection provided meaningful pain relief for about 40 days and the authors acknowledged the need for a large trial with repeated injections. No trials of multidisciplinary interventions or individualised treatments were identified. Conclusions Our systematic review highlights a lack of evidence about the effectiveness of prediction and management strategies for chronic postsurgical pain after total knee replacement. As a large number of people are affected by chronic pain after total knee replacement, development of an evidence base about care for these patients should be a research priority. PMID:25967998

  15. The Trade-Offs of Developing a Case Management Model for Chronically Mentally Ill People.

    ERIC Educational Resources Information Center

    Belcher, John R.

    1993-01-01

    Addresses role of case management in care of chronically mentally ill persons. Notes that case management can be effective if designed so that services match client needs and service costs are measured accurately. Contends that profit-maximizing nature of U.S. health care system makes some form of capitation likely in design of case management…

  16. THE INFLUENCE OF ANTITUBERCULOUS VACCINATION ON THE COURSE OF THE TUBERCULOUS PROCESS IN CHRONIC IRRADIATION (in Russian)

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

    Khudushina, T.A.

    1961-10-01

    Preliminary antituberculosis vaccination of tuberculosisinfected rabbits subjected to protracted x irradiation (10 r daily) yields a positive effect only during the first stages of irradiation. Disturbance of specific antituberculous immunity occurs in the process of development of chronic radiation sickness. At this period the tuberculous process acquires a marked exudative-necrotic character. (auth)

  17. Perchlorate disrupts embryonic androgen synthesis and reproductive development in threespine stickleback without changing whole-body levels of thyroid hormone

    PubMed Central

    Petersen, Ann M.; Dillon, Danielle; Bernhardt, Richard A.; Torunsky, Roberta; Postlethwait, John H.; von Hippel, Frank A.; Buck, C. Loren; Cresko, William A.

    2014-01-01

    Perchlorate, an environmental contaminant, disrupts normal functioning of the thyroid. We previously showed that perchlorate disrupts behavior and gonad development, and induces external morphological changes in a vertebrate model organism, the threespine stickleback. Whether perchlorate alters these phenotypes via a thyroid-mediated mechanism, and the extent to which the effects depend on dose, are unknown. To address these questions, we chronically exposed stickleback to control conditions and to three concentrations of perchlorate (10, 30 and 100 ppm) at various developmental stages from fertilization to reproductive maturity. Adults chronically exposed to perchlorate had increased numbers of thyroid follicles and decreased numbers of thyrocytes. Surprisingly, T4 and T3 levels in larval, juvenile, and adult whole fish chronically exposed to perchlorate did not differ from controls, except at the lowest perchlorate dose, suggesting a non-monotonic dose response curve. We found no detectable abnormalities in external phenotype at any dose of perchlorate, indicating that the increased number of thyroid follicles compensated for the disruptive effects of these doses. In contrast to external morphology, gonadal development was altered substantially, with the highest dose of perchlorate causing the largest effects. Perchlorate increased the number both of early stage ovarian follicles in females and of advanced spermatogenic stages in males. Perchlorate also disrupted embryonic androgen levels. We conclude that chronic perchlorate exposure may not result in lasting adult gross morphological changes but can produce lasting modifications to gonads when compensation of T3 and T4 levels occurs by thyroid follicle hyperplasia. Perchlorate may therefore affect vertebrate development via both thyroidal and non-thyroidal mechanisms. PMID:25448260

  18. Metabolic consequences of stress during childhood and adolescence.

    PubMed

    Pervanidou, Panagiota; Chrousos, George P

    2012-05-01

    Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity-related health problems. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. The effect of pH on chronic aquatic nickel toxicity is dependent on the pH itself: Extending the chronic nickel bioavailability models.

    PubMed

    Nys, Charlotte; Janssen, Colin R; Van Sprang, Patrick; De Schamphelaere, Karel A C

    2016-05-01

    The environmental quality standard for Ni in the European Commission's Water Framework Directive is bioavailability based. Although some of the available chronic Ni bioavailability models are validated only for pH ≤ 8.2, a considerable fraction of European surface waters has a pH > 8.2. Therefore, the authors investigated the effect of a change in pH from 8.2 to 8.7 on chronic Ni toxicity in 3 invertebrate (Daphnia magna, Lymnaea stagnalis, and Brachionus calyciflorus) and 2 plant species (Pseudokirchneriella subcapitata and Lemna minor). Nickel toxicity was almost always significantly higher at pH 8.7 than at pH 8.2. To test whether the existing chronic Ni bioavailability models developed for pH ≤ 8.2 can be used at higher pH levels, Ni toxicity at pH 8.7 was predicted based on Ni toxicity observed at pH 8.2. This resulted in a consistent underestimation of toxicity. The results suggest that the effect of pH on Ni(2+) toxicity is dependent on the pH itself: the slope of the pH effect is steeper above than below pH 8.2 for species for which a species-specific bioavailability model exists. Therefore, the existing chronic Ni bioavailability models were modified to allow predictions of chronic Ni toxicity to invertebrates and plants in the pH range of 8.2 to 8.7 by applying a pH slope (SpH ) dependent on the pH of the target water. These modified Ni bioavailability models resulted in more accurate predictions of Ni toxicity to all 5 species (within 2-fold error), without the bias observed using the bioavailability models developed for pH ≤ 8.2. The results of the present study can decrease the uncertainty in implementing the bioavailability-based environmental quality standard under the Water Framework Directive for high-pH regions in Europe. © 2015 SETAC.

  20. Development and validation of a metal mixture bioavailability model (MMBM) to predict chronic toxicity of Ni-Zn-Pb mixtures to Ceriodaphnia dubia.

    PubMed

    Nys, Charlotte; Janssen, Colin R; De Schamphelaere, Karel A C

    2017-01-01

    Recently, several bioavailability-based models have been shown to predict acute metal mixture toxicity with reasonable accuracy. However, the application of such models to chronic mixture toxicity is less well established. Therefore, we developed in the present study a chronic metal mixture bioavailability model (MMBM) by combining the existing chronic daphnid bioavailability models for Ni, Zn, and Pb with the independent action (IA) model, assuming strict non-interaction between the metals for binding at the metal-specific biotic ligand sites. To evaluate the predictive capacity of the MMBM, chronic (7d) reproductive toxicity of Ni-Zn-Pb mixtures to Ceriodaphnia dubia was investigated in four different natural waters (pH range: 7-8; Ca range: 1-2 mM; Dissolved Organic Carbon range: 5-12 mg/L). In each water, mixture toxicity was investigated at equitoxic metal concentration ratios as well as at environmental (i.e. realistic) metal concentration ratios. Statistical analysis of mixture effects revealed that observed interactive effects depended on the metal concentration ratio investigated when evaluated relative to the concentration addition (CA) model, but not when evaluated relative to the IA model. This indicates that interactive effects observed in an equitoxic experimental design cannot always be simply extrapolated to environmentally realistic exposure situations. Generally, the IA model predicted Ni-Zn-Pb mixture toxicity more accurately than the CA model. Overall, the MMBM predicted Ni-Zn-Pb mixture toxicity (expressed as % reproductive inhibition relative to a control) in 85% of the treatments with less than 20% error. Moreover, the MMBM predicted chronic toxicity of the ternary Ni-Zn-Pb mixture at least equally accurately as the toxicity of the individual metal treatments (RMSE Mix  = 16; RMSE Zn only  = 18; RMSE Ni only  = 17; RMSE Pb only  = 23). Based on the present study, we believe MMBMs can be a promising tool to account for the effects of water chemistry on metal mixture toxicity during chronic exposure and could be used in metal risk assessment frameworks. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes.

    PubMed

    Rompala, Gregory R; Mounier, Anais; Wolfe, Cody M; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E

    2018-01-01

    While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2 , known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of paternal exposures that can affect small noncoding RNA abundance and nucleoside modifications in sperm. As small noncoding RNAs in sperm have been shown to causally induce heritable phenotypes in offspring, additional research is warranted to understand the potential effects of ethanol-responsive sperm small noncoding RNAs on offspring health and development.

  2. Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes

    PubMed Central

    Rompala, Gregory R.; Mounier, Anais; Wolfe, Cody M.; Lin, Qishan; Lefterov, Iliya; Homanics, Gregg E.

    2018-01-01

    While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of paternal exposures that can affect small noncoding RNA abundance and nucleoside modifications in sperm. As small noncoding RNAs in sperm have been shown to causally induce heritable phenotypes in offspring, additional research is warranted to understand the potential effects of ethanol-responsive sperm small noncoding RNAs on offspring health and development. PMID:29472946

  3. Bullous pyoderma gangrenosum complicated by disseminated intravascular coagulation with subsequent myelodysplastic syndrome (chronic myelomonocytic leukemia).

    PubMed

    Rogalski, Christina; Paasch, Uwe; Glander, Hans-Jürgen; Haustein, Uwe-Frithjof

    2003-01-01

    A 33-year-old woman developed a bullous PG precursing a chronic myelomonocytic leukemia (CMML) complicated by life-threatening, disseminated, intravascular coagulation after administration of systemic corticosteroids in combination with immunosuppressant and antibiotic agents. Although the association between PG and leukemia, as well as the coincidence of disseminated intravascular coagulation (DIC) and leukemia, is well known, a premonitoring effect of PG in combination with DIC preceding the diagnosis of chronic myelomonocytic leukemia in the same patient has not been reported recently.

  4. Disease drivers of aging

    PubMed Central

    Hodes, Richard J.; Sierra, Felipe; Austad, Steven N.; Epel, Elissa; Neigh, Gretchen N.; Erlandson, Kristine M.; Schafer, Marissa J.; LeBrasseur, Nathan K.; Wiley, Christopher; Campisi, Judith; Sehl, Mary E.; Scalia, Rosario; Eguchi, Satoru; Kasinath, Balakuntalam S.; Halter, Jeffrey B.; Cohen, Harvey Jay; Demark-Wahnefried, Wendy; Ahles, Tim A.; Barzilai, Nir; Hurria, Arti; Hunt, Peter W.

    2017-01-01

    It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship—the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. PMID:27943360

  5. Cost-effectiveness analysis of a randomized trial comparing care models for chronic kidney disease.

    PubMed

    Hopkins, Robert B; Garg, Amit X; Levin, Adeera; Molzahn, Anita; Rigatto, Claudio; Singer, Joel; Soltys, George; Soroka, Steven; Parfrey, Patrick S; Barrett, Brendan J; Goeree, Ron

    2011-06-01

    Potential cost and effectiveness of a nephrologist/nurse-based multifaceted intervention for stage 3 to 4 chronic kidney disease are not known. This study examines the cost-effectiveness of a chronic disease management model for chronic kidney disease. Cost and cost-effectiveness were prospectively gathered alongside a multicenter trial. The Canadian Prevention of Renal and Cardiovascular Endpoints Trial (CanPREVENT) randomized 236 patients to receive usual care (controls) and another 238 patients to multifaceted nurse/nephrologist-supported care that targeted factors associated with development of kidney and cardiovascular disease (intervention). Cost and outcomes over 2 years were examined to determine the incremental cost-effectiveness of the intervention. Base-case analysis included disease-related costs, and sensitivity analysis included all costs. Consideration of all costs produced statistically significant differences. A lower number of days in hospital explained most of the cost difference. For both base-case and sensitivity analyses with all costs included, the intervention group required fewer resources and had higher quality of life. The direction of the results was unchanged to inclusion of various types of costs, consideration of payer or societal perspective, changes to the discount rate, and levels of GFR. The nephrologist/nurse-based multifaceted intervention represents good value for money because it reduces costs without reducing quality of life for patients with chronic kidney disease.

  6. [Development of lipoma following a single cupping massage - a case report].

    PubMed

    Schumann, Stefan; Lauche, Romy; Hohmann, Claudia; Zirbes, Thomas; Dobos, Gustav; Saha, Felix Joyonto

    2012-01-01

    The cupping massage is a form of bloodless cupping. This type of cupping is particularly used to treat muscular tension and musculoskeletal pain, such as chronic neck pain; however the data records on mechanisms and potential side effects are not satisfactory. In a study on the effectiveness of cupping massage in patients with chronic neck pain, one patient showed a formation of a lipoma in the cupping area after the first treatment session. Because of the short time interval between therapy and development of the lipoma, a primary cause is not realistic. This adverse event has not been described in the literature before, and the present report describes the case in summary.

  7. Naltrexone modulates dopamine release following chronic, but not acute amphetamine administration: a translational study

    PubMed Central

    Jayaram-Lindström, N; Guterstam, J; Häggkvist, J; Ericson, M; Malmlöf, T; Schilström, B; Halldin, C; Cervenka, S; Saijo, T; Nordström, A-L; Franck, J

    2017-01-01

    The opioid antagonist naltrexone has been shown to attenuate the subjective effects of amphetamine. However, the mechanisms behind this modulatory effect are currently unknown. We hypothesized that naltrexone would diminish the striatal dopamine release induced by amphetamine, which is considered an important mechanism behind many of its stimulant properties. We used positron emission tomography and the dopamine D2-receptor radioligand [11C]raclopride in healthy subjects to study the dopaminergic effects of an amphetamine injection after pretreatment with naltrexone or placebo. In a rat model, we used microdialysis to study the modulatory effects of naltrexone on dopamine levels after acute and chronic amphetamine exposure. In healthy humans, naltrexone attenuated the subjective effects of amphetamine, confirming our previous results. Amphetamine produced a significant reduction in striatal radioligand binding, indicating increased levels of endogenous dopamine. However, there was no statistically significant effect of naltrexone on dopamine release. The same pattern was observed in rats, where an acute injection of amphetamine caused a significant rise in striatal dopamine levels, with no effect of naltrexone pretreatment. However, in a chronic model, naltrexone significantly attenuated the dopamine release caused by reinstatement of amphetamine. Collectively, these data suggest that the opioid system becomes engaged during the more chronic phase of drug use, evidenced by the modulatory effect of naltrexone on dopamine release following chronic amphetamine administration. The importance of opioid-dopamine interactions in the reinforcing and addictive effects of amphetamine is highlighted by the present findings and may help to facilitate medication development in the field of stimulant dependence. PMID:28440810

  8. Association between organizational capacity and involvement in chronic disease prevention programming among Canadian public health organizations

    PubMed Central

    Hanusaik, Nancy; Sabiston, Catherine M.; Kishchuk, Natalie; Maximova, Katerina; O’Loughlin, Jennifer

    2015-01-01

    In the context of the emerging field of public health services and systems research, this study (i) tested a model of the relationships between public health organizational capacity (OC) for chronic disease prevention, its determinants (organizational supports for evaluation, partnership effectiveness) and one possible outcome of OC (involvement in core chronic disease prevention practices) and (ii) examined differences in the nature of these relationships among organizations operating in more and less facilitating external environments. OC was conceptualized as skills and resources/supports for chronic disease prevention programming. Data were from a census of 210 Canadian public health organizations with mandates for chronic disease prevention. The hypothesized relationships were tested using structural equation modeling. Overall, the results supported the model. Organizational supports for evaluation accounted for 33% of the variance in skills. Skills and resources/supports were directly and strongly related to involvement. Organizations operating within facilitating external contexts for chronic disease prevention had more effective partnerships, more resources/supports, stronger skills and greater involvement in core chronic disease prevention practices. Results also suggested that organizations functioning in less facilitating environments may not benefit as expected from partnerships. Empirical testing of this conceptual model helps develop a better understanding of public health OC. PMID:25361958

  9. Impact of the mitochondria-targeted antioxidant MitoQ on hypoxia-induced pulmonary hypertension.

    PubMed

    Pak, Oleg; Scheibe, Susan; Esfandiary, Azadeh; Gierhardt, Mareike; Sydykov, Akylbek; Logan, Angela; Fysikopoulos, Athanasios; Veit, Florian; Hecker, Matthias; Kroschel, Florian; Quanz, Karin; Erb, Alexandra; Schäfer, Katharina; Fassbinder, Mirja; Alebrahimdehkordi, Nasim; Ghofrani, Hossein A; Schermuly, Ralph T; Brandes, Ralf P; Seeger, Werner; Murphy, Michael P; Weissmann, Norbert; Sommer, Natascha

    2018-02-01

    Increased mitochondrial reactive oxygen species (ROS), particularly superoxide have been suggested to mediate hypoxic pulmonary vasoconstriction (HPV), chronic hypoxia-induced pulmonary hypertension (PH) and right ventricular (RV) remodelling.We determined ROS in acute, chronic hypoxia and investigated the effect of the mitochondria-targeted antioxidant MitoQ under these conditions.The effect of MitoQ or its inactive carrier substance, decyltriphenylphosphonium (TPP + ), on acute HPV (1% O 2 for 10 minutes) was investigated in isolated blood-free perfused mouse lungs. Mice exposed for 4 weeks to chronic hypoxia (10% O 2 ) or after banding of the main pulmonary artery (PAB) were treated with MitoQ or TPP + (50 mg/kg/day).Total cellular superoxide and mitochondrial ROS levels were increased in pulmonary artery smooth muscle cells (PASMC), but decreased in pulmonary fibroblasts in acute hypoxia. MitoQ significantly inhibited HPV and acute hypoxia-induced rise in superoxide concentration. ROS was decreased in PASMC, while it increased in the RV after chronic hypoxia. Correspondingly, MitoQ did not affect the development of chronic hypoxia-induced PH, but attenuated RV remodelling after chronic hypoxia as well as after PAB.Increased mitochondrial ROS of PASMC mediate acute HPV, but not chronic hypoxia-induced PH. MitoQ may be beneficial under conditions of exaggerated acute HPV. Copyright ©ERS 2018.

  10. Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

    PubMed

    Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

    2011-01-01

    Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

  11. Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

    PubMed

    Langgartner, Dominik; Wachter, Ulrich; Hartmann, Clair; Gröger, Michael; Vogt, Josef; Merz, Tamara; McCook, Oscar; Fink, Marina; Kress, Sandra; Georgieff, Michael; Kunze, Julia F; Radermacher, Peter L; Reber, Stefan O; Wepler, Martin

    2018-06-08

    Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multiple-organ-failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

  12. The Effect of Photodynamic Therapy in the Treatment of Chronic Periodontitis: A Review of Literature.

    PubMed

    Meimandi, Mansour; Talebi Ardakani, Mohammad Reza; Esmaeil Nejad, Azadeh; Yousefnejad, Parisa; Saebi, Khosro; Tayeed, Mohammad Hossein

    2017-01-01

    Introduction: Chronic periodontitis is the most common periodontal disease which is related to the chronic accumulation of bacterial plaque. Since mechanical methods are not sufficient in the treatment of this disease, administration of local/systemic antibiotic is recommended following mechanical debridement. However, side effects of antibiotics such as microbial resistance and patient allergy led to development of alternative methods. One of these suggested methods is the antimicrobial photodynamic therapy (aPDT). PDT is a local noninvasive treatment modality without the side effects caused by antibiotics. The aim of this study was to review the articles related to the application of PDT with laser in the treatment of chronic periodontitis. Review of literature: In the present review of literature, the authors used key words such as chronic periodontitis, laser and photodynamic therapy, and conducted a literature search via Google Scholar and PubMed for the period of 1990 to 2015. A total of 47 articles in English were found. The articles that were not associated with the topic of research and review articles were deleted and only clinical trials were evaluated. After reviewing 23 articles' abstracts, the full texts of 16 articles were analyzed. Conclusion: Considering the safety, the lack of side effects and general advantages like more patient compliance, the PDT treatment with scaling and root planing (SRP) is recommended as an efficient adjunctive modality for the treatment of localized chronic periodontitis especially during the maintenance phase in non-surgical treatment.

  13. COPD and chronic bronchitis risk of indoor air pollution from solid fuel: a systematic review and meta-analysis.

    PubMed

    Kurmi, Om P; Semple, Sean; Simkhada, Padam; Smith, W Cairns S; Ayres, Jon G

    2010-03-01

    Over half the world is exposed daily to the smoke from combustion of solid fuels. Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease and can be caused by biomass smoke exposure. However, studies of biomass exposure and COPD show a wide range of effect sizes. The aim of this systematic review was to quantify the impact of biomass smoke on the development of COPD and define reasons for differences in the reported effect sizes. A systematic review was conducted of studies with sufficient statistical power to calculate the health risk of COPD from the use of solid fuel, which followed standardised criteria for the diagnosis of COPD and which dealt with confounding factors. The results were pooled by fuel type and country to produce summary estimates using a random effects model. Publication bias was also estimated. There were positive associations between the use of solid fuels and COPD (OR=2.80, 95% CI 1.85 to 4.0) and chronic bronchitis (OR=2.32, 95% CI 1.92 to 2.80). Pooled estimates for different types of fuel show that exposure to wood smoke while performing domestic work presents a greater risk of development of COPD and chronic bronchitis than other fuels. Despite heterogeneity across the selected studies, exposure to solid fuel smoke is consistently associated with COPD and chronic bronchitis. Efforts should be made to reduce exposure to solid fuel by using either cleaner fuel or relatively cleaner technology while performing domestic work.

  14. Preventive and Therapeutic Role of Functional Ingredients of Barley Grass for Chronic Diseases in Human Beings

    PubMed Central

    Du, Juan; Yang, Xiaomeng; Li, Xia; Li, Ling; Zhou, Yan; Yang, Tao

    2018-01-01

    Barley grass powder is the best functional food that provides nutrition and eliminates toxins from cells in human beings; however, its functional ingredients have played an important role as health benefit. In order to better cognize the preventive and therapeutic role of barley grass for chronic diseases, we carried out the systematic strategies for functional ingredients of barley grass, based on the comprehensive databases, especially the PubMed, Baidu, ISI Web of Science, and CNKI, between 2008 and 2017. Barley grass is rich in functional ingredients, such as gamma-aminobutyric acid (GABA), flavonoids, saponarin, lutonarin, superoxide dismutase (SOD), K, Ca, Se, tryptophan, chlorophyll, vitamins (A, B1, C, and E), dietary fiber, polysaccharide, alkaloid, metallothioneins, and polyphenols. Barley grass promotes sleep; has antidiabetic effect; regulates blood pressure; enhances immunity; protects liver; has anti-acne/detoxifying and antidepressant effects; improves gastrointestinal function; has anticancer, anti-inflammatory, antioxidant, hypolipidemic, and antigout effects; reduces hyperuricemia; prevents hypoxia, cardiovascular diseases, fatigue, and constipation; alleviates atopic dermatitis; is a calcium supplement; improves cognition; and so on. These results support that barley grass may be one of the best functional foods for preventive chronic diseases and the best raw material of modern diet structure in promoting the development of large health industry and further reveal that GABA, flavonoids, SOD, K-Ca, vitamins, and tryptophan mechanism of barley grass have preventive and therapeutic role for chronic diseases. This paper can be used as a scientific evidence for developing functional foods and novel drugs for barley grass for preventive chronic diseases.

  15. Personality traits and chronic disease: implications for adult personality development.

    PubMed

    Sutin, Angelina R; Zonderman, Alan B; Ferrucci, Luigi; Terracciano, Antonio

    2013-11-01

    Personality traits have been associated with chronic disease. Less is known about the longitudinal relation between personality and disease and whether chronic disease is associated with changes in personality. Method. Participants from the Baltimore Longitudinal Study of Aging (N = 2,008) completed the Revised NEO Personality Inventory and a standard medical interview at regularly scheduled visits; the Charlson Comorbidity Index, a weighted sum of 19 serious diseases, was derived from this interview. Using data from 6,685 visits, we tested whether personality increased risk of disease and whether disease was associated with personality change. Measured concurrently, neuroticism and conscientiousness were associated with greater disease burden. The impulsiveness facet of neuroticism was the strongest predictor of developing disease across the follow-up period: For every standard deviation increase in impulsiveness, there was a 26% increased risk of developing disease and a 36% increased risk of getting more ill. Personality traits changed only modestly with disease: As participants developed chronic illnesses, they became more conservative (decreased openness). Discussion. This research indicates that personality traits confer risk for disease, in part, through health-risk behaviors. These traits, however, were relatively resistant to the effect of serious disease.

  16. Patients’ Acceptance of Smartphone Health Technology for Chronic Disease Management: A Theoretical Model and Empirical Test

    PubMed Central

    Dou, Kaili; Yu, Ping; Liu, Fang; Guan, YingPing; Li, Zhenye; Ji, Yumeng; Du, Ningkai; Lu, Xudong; Duan, Huilong

    2017-01-01

    Background Chronic disease patients often face multiple challenges from difficult comorbidities. Smartphone health technology can be used to help them manage their conditions only if they accept and use the technology. Objective The aim of this study was to develop and test a theoretical model to predict and explain the factors influencing patients’ acceptance of smartphone health technology for chronic disease management. Methods Multiple theories and factors that may influence patients’ acceptance of smartphone health technology have been reviewed. A hybrid theoretical model was built based on the technology acceptance model, dual-factor model, health belief model, and the factors identified from interviews that might influence patients’ acceptance of smartphone health technology for chronic disease management. Data were collected from patient questionnaire surveys and computer log records about 157 hypertensive patients’ actual use of a smartphone health app. The partial least square method was used to test the theoretical model. Results The model accounted for .412 of the variance in patients’ intention to adopt the smartphone health technology. Intention to use accounted for .111 of the variance in actual use and had a significant weak relationship with the latter. Perceived ease of use was affected by patients’ smartphone usage experience, relationship with doctor, and self-efficacy. Although without a significant effect on intention to use, perceived ease of use had a significant positive influence on perceived usefulness. Relationship with doctor and perceived health threat had significant positive effects on perceived usefulness, countering the negative influence of resistance to change. Perceived usefulness, perceived health threat, and resistance to change significantly predicted patients’ intentions to use the technology. Age and gender had no significant influence on patients’ acceptance of smartphone technology. The study also confirmed the positive relationship between intention to use and actual use of smartphone health apps for chronic disease management. Conclusions This study developed a theoretical model to predict patients’ acceptance of smartphone health technology for chronic disease management. Although resistance to change is a significant barrier to technology acceptance, careful management of doctor-patient relationship, and raising patients’ awareness of the negative effect of chronic disease can negate the effect of resistance and encourage acceptance and use of smartphone health technology to support chronic disease management for patients in the community. PMID:29212629

  17. [The remote effects of chronic exposure to ionizing radiation and electromagnetic fields with respect to hygienic standardization].

    PubMed

    Grigor'ev, Iu G; Shafirkin, A V; Nikitina, V N; Vasin, A L

    2003-01-01

    A variety and rate of non-cancer diseases occurred in humans as a result of chronic exposure to ionizing radiation or to electromagnetic radiation (EMR) of high and superhigh frequency have been compared. The intensity of EMR was slightly higher than a sanitary standard for population. A risk of health impairments in workers having occupational exposure to EMR was assessed on the basis of Selie's concept of development of non-specific reaction of the body to chronic stress factors (general adaptation syndrome), models of changes in the body compensatory reserves and calculations of radiation risk after severe and chronic exposure to ionizing radiation.

  18. Development and evaluation of a behavioral pain management treatment program in a Veterans Affairs Medical Center.

    PubMed

    Stratton, Kelcey J; Bender, Mark C; Cameron, Jennifer J; Pickett, Treven C

    2015-03-01

    Chronic pain complaints are highly prevalent among Veterans seeking Veterans Affairs health care, and the implementation of effective behavioral health interventions is vital to meet patient needs. Research supports the use of cognitive behavioral therapy for the treatment of chronic pain; however, varying guidelines regarding length of treatment and modality (i.e., group vs. individual) complicate clinical planning and program development. This study aimed to evaluate treatment outcomes and equivalence of 3 variations (12, 10, and 6 weeks of group treatment) of cognitive behavioral therapy for chronic pain using clinical program data collected from Veterans enrolled in Veterans Affairs health services in a large tertiary care setting. Across groups, Veterans showed improvements in negative pain-related thinking and decreases in pain-related disability and distress. In general, patient outcomes regarding pain-related distress and disability for the 6-week group were equivalent or better than the 12- and 10-week groups. Preliminary results support the effectiveness of brief behavioral interventions for chronic pain. The findings have important practical implications, as briefer treatments may offer comparable therapeutic impact as longer, more time-intensive treatment protocols. This study offers a unique examination of treatment development and evaluation processes informed by real-world clinical needs and patient feedback. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  19. The role of pulmonology in the National Health System Chronicity Strategy.

    PubMed

    Soler-Cataluña, Juan José; Sánchez Toril, Fernando; Aguar Benito, M Carmen

    2015-08-01

    Longer life expectancy and the progressive aging of the population is changing the epidemiological pattern of healthcare, with a reduction in the incidence of acute diseases and a marked increase in chronic diseases. This change brings important social, healthcare and economic consequences that call for a reorganization of patient care. In this respect, the Spanish National Health System has developed a Chronicity strategy that proposes a substantial change in focus from traditional rescue medicine to patient- and environment-centered care, with a planned, proactive, participative and multidisciplinary approach. Some of the more common chronic diseases are respiratory. In COPD, this integrated approach has been effective in reducing exacerbations, improving quality of life, and even reducing costs. However, the wide variety of management strategies, not only in COPD but also in asthma and other respiratory diseases, makes it difficult to draw definitive conclusions. Pulmonologists can and must participate in the new chronicity models and contribute their knowledge, experience, innovation, research, and special expertise to the development of these new paradigms. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  20. Tobacco-related disease burden and preventive initiatives in China. Global health and the chronic diseases: perspective, policy and practice.

    PubMed

    Niu, Bolin

    2011-06-01

    The burden of chronic diseases in global health is a surging area of research. The Global Health Initiative at the National Heart, Lung, and Blood Institute brings together investigators from developing countries with those from the developed world to study these diseases. In China, approximately 83 percent of all deaths in 2000 were attributed to chronic illnesses, which are the research focuses of the Chinese center of the Global Health Initiative. Tobacco use as well as passive smoking are modifiable risk factors in a large number of such chronic conditions. The prevalence of smoking in China is extensive and has inseparable ties to the economy, with tobacco taxes making up a large portion of government revenue in poorer provinces. Methods of smoking prevention have been piloted in some Chinese schools, which have mitigated the increase in smoking rate but have not resulted in a primary preventive effect. Efforts by the Yale Global Health Initiative and the Yale-China Association are bringing researchers together to address chronic disease in China as Yale School of Medicine enters its 200th year.

  1. Ageing and the border between health and disease.

    PubMed

    MacNee, William; Rabinovich, Roberto A; Choudhury, Gourab

    2014-11-01

    Ageing is associated with a progressive degeneration of the tissues, which has a negative impact on the structure and function of vital organs and is among the most important known risk factors for most chronic diseases. Since the proportion of the world's population aged >60 years will double in the next four decades, this will be accompanied by an increased incidence of chronic age-related diseases that will place a huge burden on healthcare resources. There is increasing evidence that many chronic inflammatory diseases represent an acceleration of the ageing process. Chronic pulmonary diseases represents an important component of the increasingly prevalent multiple chronic debilitating diseases, which are a major cause of morbidity and mortality, particularly in the elderly. The lungs age and it has been suggested that chronic obstructive pulmonary disease (COPD) is a condition of accelerated lung ageing and that ageing may provide a mechanistic link between COPD and many of its extrapulmonary effects and comorbidities. In this article we will describe the physiological changes and mechanisms of ageing, with particular focus on the pulmonary effects of ageing and how these may be relevant to the development of COPD and its major extrapulmonary manifestations. ©ERS 2014.

  2. The Effect of a Common Antibiotics Doxycycline on Non-Healing Chronic Wound.

    PubMed

    Xu, Dixon H; Zhu, Ziwen; Fang, Yujiang

    2017-01-01

    Up to 25% of diabetic patients will develop a diabetic foot ulcer. Chronic wounds such as diabetic foot ulcers often fail to heal with conventional therapies. In recent years, it has been identified that chronic wounds are usually associated with elevated level of matrix metalloproteinases (MMPs). Doxycycline, a cheap tetracycline antibiotic, has been shown to inhibit MMPs both in vitro and in vivo independent of its antimicrobial property. We undertook a search through PUBMED for peer-reviewed research literature with doxycycline, chronic wound, diabetes, MMPs as key words. Seventy papers were included in the review. This review identified doxycycline is a very promising drug to be used in patients with diabetic foot ulcers because higher efficacy even in a very low dosage, little side effects in a lower dosage, inhibition of MMP as well as prevention/treatment of infection in the ulcers, beneficial to cardiovascular complications and cheap to manufacture. In this review, we provide an overview of the roles of MMPs in the pathogenesis of chronic wounds and explore the potential application of doxycycline as a treatment option in managing chronic wounds such as diabetic foot ulcers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Developing a Framework to Generate Evidence of Health Outcomes From Social Media Use in Chronic Disease Management

    PubMed Central

    Gray, Kathleen; Martin-Sanchez, Fernando

    2013-01-01

    Background While there is an abundance of evidence-based practice (EBP) recommendations guiding management of various chronic diseases, evidence suggesting best practice for using social media to improve health outcomes is inadequate. The variety of social media platforms, multiple potential uses, inconsistent definitions, and paucity of rigorous studies, make it difficult to measure health outcomes reliably in chronic disease management. Most published investigations report on an earlier generation of online tools, which are not as user-centered, participatory, engaging, or collaborative, and thus may work differently for health self-management. Objective The challenge to establish a sound evidence base for social media use in chronic disease starts with the need to define criteria and methods to generate and evaluate evidence. The authors’ key objective is to develop a framework for research and practice that addresses this challenge. Methods This paper forms part of a larger research project that presents a conceptual framework of how evidence of health outcomes can be generated from social media use, allowing social media to be utilized in chronic disease management more effectively. Using mixed methods incorporating a qualitative literature review, a survey and a pilot intervention, the research closely examines the therapeutic affordances of social media, people with chronic pain (PWCP) as a subset of chronic disease management, valid outcome measurement of patient-reported (health) outcomes (PRO), the individual needs of people living with chronic disease, and finally translation of the combined results to improve evidence-based decision making about social media use in this context. Results Extensive review highlights various affordances of social media that may prove valuable to understanding social media’s effect on individual health outcomes. However, without standardized PRO instruments, we are unable to definitively investigate these effects. The proposed framework that we offer outlines how therapeutic affordances of social media coupled with valid and reliable PRO measurement may be used to generate evidence of improvements in health outcomes, as well as guide evidence-based decision making in the future about social media use as part of chronic disease self-management. Conclusions The results will (1) inform a framework for conducting research into health outcomes from social media use in chronic disease, as well as support translating the findings into evidence of improved health outcomes, and (2) inform a set of recommendations for evidence-based decision making about social media use as part of chronic disease self-management. These outcomes will fill a gap in the knowledge and resources available to individuals managing a chronic disease, their clinicians and other researchers in chronic disease and the field of medicine 2.0. PMID:25075238

  4. Developing a framework to generate evidence of health outcomes from social media use in chronic disease management.

    PubMed

    Merolli, Mark; Gray, Kathleen; Martin-Sanchez, Fernando

    2013-01-01

    While there is an abundance of evidence-based practice (EBP) recommendations guiding management of various chronic diseases, evidence suggesting best practice for using social media to improve health outcomes is inadequate. The variety of social media platforms, multiple potential uses, inconsistent definitions, and paucity of rigorous studies, make it difficult to measure health outcomes reliably in chronic disease management. Most published investigations report on an earlier generation of online tools, which are not as user-centered, participatory, engaging, or collaborative, and thus may work differently for health self-management. The challenge to establish a sound evidence base for social media use in chronic disease starts with the need to define criteria and methods to generate and evaluate evidence. The authors' key objective is to develop a framework for research and practice that addresses this challenge. This paper forms part of a larger research project that presents a conceptual framework of how evidence of health outcomes can be generated from social media use, allowing social media to be utilized in chronic disease management more effectively. Using mixed methods incorporating a qualitative literature review, a survey and a pilot intervention, the research closely examines the therapeutic affordances of social media, people with chronic pain (PWCP) as a subset of chronic disease management, valid outcome measurement of patient-reported (health) outcomes (PRO), the individual needs of people living with chronic disease, and finally translation of the combined results to improve evidence-based decision making about social media use in this context. Extensive review highlights various affordances of social media that may prove valuable to understanding social media's effect on individual health outcomes. However, without standardized PRO instruments, we are unable to definitively investigate these effects. The proposed framework that we offer outlines how therapeutic affordances of social media coupled with valid and reliable PRO measurement may be used to generate evidence of improvements in health outcomes, as well as guide evidence-based decision making in the future about social media use as part of chronic disease self-management. The results will (1) inform a framework for conducting research into health outcomes from social media use in chronic disease, as well as support translating the findings into evidence of improved health outcomes, and (2) inform a set of recommendations for evidence-based decision making about social media use as part of chronic disease self-management. These outcomes will fill a gap in the knowledge and resources available to individuals managing a chronic disease, their clinicians and other researchers in chronic disease and the field of medicine 2.0.

  5. Surgical treatment of chronic pancreatitis in young patients.

    PubMed

    Zhou, Feng; Gou, Shan-Miao; Xiong, Jiong-Xin; Wu, He-Shui; Wang, Chun-You; Liu, Tao

    2014-10-01

    The main treatment strategies for chronic pancreatitis in young patients include therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) intervention and surgical intervention. Therapeutic ERCP intervention is performed much more extensively for its minimally invasive nature, but a part of patients are referred to surgery at last. Historical and follow-up data of 21 young patients with chronic pancreatitis undergoing duodenum-preserving total pancreatic head resection were analyzed to evaluate the outcomes of therapeutic ERCP intervention and surgical intervention in this study. The surgical complications of repeated therapeutic ERCP intervention and surgical intervention were 38% and 19% respectively. During the first therapeutic ERCP intervention to surgical intervention, 2 patients developed diabetes, 5 patients developed steatorrhea, and 5 patients developed pancreatic type B pain. During the follow-up of surgical intervention, 1 new case of diabetes occurred, 1 case of steatorrhea recovered, and 4 cases of pancreatic type B pain were completely relieved. In a part of young patients with chronic pancreatitis, surgical intervention was more effective than therapeutic ERCP intervention on delaying the progression of the disease and relieving the symptoms.

  6. Chronic swine instrumentation techniques utilizing the GOR-REX peritoneal catheter

    NASA Astrophysics Data System (ADS)

    Gray, C. C.; White, F. C.; Crisman, R. P.; Wisniewski, J.; McKirnan, D.

    1985-05-01

    The GORE-TEX peritoneal catheter interface is an effective skin interface device for many types of instrumentation in the swine. When properly utilized, the interface allows the development of a stable and effective biological seal which will reduce or eliminate sinus tract formation and resultant systemic infection. The interface is suitable for running any wire or catheter (up to about 2.5mm diameter) through the integument of the animal, thus increasing the possibilities for chronic instrumentation while maintaining a healthy animal. The lack of evidence of any growth phenomenon acting to extrude the interface segment, similar to that observed using other synthetic materials, and the superior biological seal which the interface develops, may allow many chronic studies which were previously not feasible. Using special catheter adapter stubs and an intermittent infusion plug, a sterile, sealed catheter system has decreased the possibilities for introducing pathogens while allowing ready access to the blood stream. Detailed descriptions of surgical implantation techniques and catheter set up and maintenance techniques are included.

  7. Military-related traumatic brain injury and neurodegeneration

    PubMed Central

    McKee, Ann C.; Robinson, Meghan E.

    2014-01-01

    Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long-term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long-term gray and white matter atrophy, precipitate or accelerate age-related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early-stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus; septal abnormalities; and abnormal deposits of hyperphosphorylated tau as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings. PMID:24924675

  8. Military-related traumatic brain injury and neurodegeneration.

    PubMed

    McKee, Ann C; Robinson, Meghan E

    2014-06-01

    Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long-term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long-term gray and white matter atrophy, precipitate or accelerate age-related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early-stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus; septal abnormalities; and abnormal deposits of hyperphosphorylated tau as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings. Copyright © 2014. Published by Elsevier Inc.

  9. Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

    PubMed Central

    Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

    2013-01-01

    The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

  10. Vascular Endothelial Cell-Specific Connective Tissue Growth Factor (CTGF) Is Necessary for Development of Chronic Hypoxia-Induced Pulmonary Hypertension.

    PubMed

    Pi, Liya; Fu, Chunhua; Lu, Yuanquing; Zhou, Junmei; Jorgensen, Marda; Shenoy, Vinayak; Lipson, Kenneth E; Scott, Edward W; Bryant, Andrew J

    2018-01-01

    Chronic hypoxia frequently complicates the care of patients with interstitial lung disease, contributing to the development of pulmonary hypertension (PH), and premature death. Connective tissue growth factor (CTGF), a matricellular protein of the Cyr61/CTGF/Nov (CCN) family, is known to exacerbate vascular remodeling within the lung. We have previously demonstrated that vascular endothelial-cell specific down-regulation of CTGF is associated with protection against the development of PH associated with hypoxia, though the mechanism for this effect is unknown. In this study, we generated a transgenic mouse line in which the Ctgf gene was floxed and deleted in vascular endothelial cells that expressed Cre recombinase under the control of VE-Cadherin promoter (eCTGF KO mice). Lack of vascular endothelial-derived CTGF protected against the development of PH secondary to chronic hypoxia, as well as in another model of bleomycin-induced pulmonary hypertension. Importantly, attenuation of PH was associated with a decrease in infiltrating inflammatory cells expressing CD11b or integrin α M (ITGAM), a known adhesion receptor for CTGF, in the lungs of hypoxia-exposed eCTGF KO mice. Moreover, these pathological changes were associated with activation of-Rho GTPase family member-cell division control protein 42 homolog (Cdc42) signaling, known to be associated with alteration in endothelial barrier function. These data indicate that endothelial-specific deletion of CTGF results in protection against development of chronic-hypoxia induced PH. This protection is conferred by both a decrease in inflammatory cell recruitment to the lung, and a reduction in lung Cdc42 activity. Based on our studies, CTGF inhibitor treatment should be investigated in patients with PH associated with chronic hypoxia secondary to chronic lung disease.

  11. The neuropathology of traumatic brain injury.

    PubMed

    Mckee, Ann C; Daneshvar, Daniel H

    2015-01-01

    Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at autopsy; however, promising efforts to develop imaging, spinal fluid, and peripheral blood biomarkers are underway to diagnose and monitor the course of disease in living subjects. © 2015 Elsevier B.V. All rights reserved.

  12. Effects of Chronic Ascariasis and Trichuriasis on Cytokine Production and Gene Expression in Human Blood: A Cross-Sectional Study

    PubMed Central

    Benitez, Susana; Broncano, Nely; Chico, Martha E.; Vaca, Maritza; Alexander, Neal; Lewis, David J.; Dougan, Gordon; Cooper, Philip J.

    2011-01-01

    Background Chronic soil-transmitted helminth (STH) infections are associated with effects on systemic immune responses that could be caused by alterations in immune homeostasis. To investigate this, we measured the impact in children of STH infections on cytokine responses and gene expression in unstimulated blood. Methodology/Principal Findings Sixty children were classified as having chronic, light, or no STH infections. Peripheral blood mononuclear cells were cultured in medium for 5 days to measure cytokine accumulation. RNA was isolated from peripheral blood and gene expression analysed using microarrays. Different infection groups were compared for the purpose of analysis: STH infection (combined chronic and light vs. uninfected groups) and chronic STH infection (chronic vs. combined light and uninfected groups). The chronic STH infection effect was associated with elevated production of GM-CSF (P = 0.007), IL-2 (P = 0.03), IL-5 (P = 0.01), and IL-10 (P = 0.01). Data reduction suggested that chronic infections were primarily associated with an immune phenotype characterized by elevated IL-5 and IL-10, typical of a modified Th2-like response. Chronic STH infections were associated with the up-regulation of genes associated with immune homeostasis (IDO, P = 0.03; CCL23, P = 0.008, HRK, P = 0.005), down-regulation of microRNA hsa-let-7d (P = 0.01) and differential regulation of several genes associated with granulocyte-mediated inflammation (IL-8, down-regulated, P = 0.0002; RNASE2, up-regulated, P = 0.009; RNASE3, up-regulated, p = 0.03). Conclusions/Significance Chronic STH infections were associated with a cytokine response indicative of a modified Th2 response. There was evidence that STH infections were associated with a pattern of gene expression suggestive of the induction of homeostatic mechanisms, the differential expression of several inflammatory genes and the down-regulation of microRNA has-let-7d. Effects on immune homeostasis and the development of a modified Th2 immune response during chronic STH infections could explain the systemic immunologic effects that have been associated with these infections such as impaired immune responses to vaccines and the suppression of inflammatory diseases. PMID:21666788

  13. Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment.

    PubMed

    Cowley, D S; Roy-Byrne, P P; Radant, A; Ritchie, J C; Greenblatt, D J; Nemeroff, C B; Hommer, D W

    1995-04-01

    The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment.

  14. Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

    PubMed Central

    Zhao, Zhengqing; Zhao, Xiangxiang; Veasey, Sigrid C.

    2017-01-01

    Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance. PMID:28620347

  15. Neural Consequences of Chronic Short Sleep: Reversible or Lasting?

    PubMed

    Zhao, Zhengqing; Zhao, Xiangxiang; Veasey, Sigrid C

    2017-01-01

    Approximately one-third of adolescents and adults in developed countries regularly experience insufficient sleep across the school and/or work week interspersed with weekend catch up sleep. This common practice of weekend recovery sleep reduces subjective sleepiness, yet recent studies demonstrate that one weekend of recovery sleep may not be sufficient in all persons to fully reverse all neurobehavioral impairments observed with chronic sleep loss, particularly vigilance. Moreover, recent studies in animal models demonstrate persistent injury to and loss of specific neuron types in response to chronic short sleep (CSS) with lasting effects on sleep/wake patterns. Here, we provide a comprehensive review of the effects of chronic sleep disruption on neurobehavioral performance and injury to neurons, astrocytes, microglia, and oligodendrocytes and discuss what is known and what is not yet established for reversibility of neural injury. Recent neurobehavioral findings in humans are integrated with animal model research examining long-term consequences of sleep loss on neurobehavioral performance, brain development, neurogenesis, neurodegeneration, and connectivity. While it is now clear that recovery of vigilance following short sleep requires longer than one weekend, less is known of the impact of CSS on cognitive function, mood, and brain health long term. From work performed in animal models, CSS in the young adult and short-term sleep loss in critical developmental windows can have lasting detrimental effects on neurobehavioral performance.

  16. Effects of multiple life stage exposure to the fungicide prochloraz in Xenopus laevis: Manifestations of antiandrogenic and other modes of toxicity

    EPA Science Inventory

    The Larval Amphibian Growth and Development Assay (LAGDA) is an internationally harmonized testing guideline for evaluating effects of chronic chemical exposure in amphibians. To evaluate the utility of the assay design during the development phase antiandrogen prochloraz was te...

  17. Protocol for the Individual Placement and Support (IPS) in Pain Trial: A randomized controlled trial investigating the effectiveness of IPS for patients with chronic pain.

    PubMed

    Linnemørken, Lene Therese B; Sveinsdottir, Vigdis; Knutzen, Thomas; Rødevand, Linn; Hernæs, Kjersti Helene; Reme, Silje Endresen

    2018-02-13

    Work disability involves large costs to the society as well as to the individual. Work disability is common among people with chronic pain conditions, yet few effective interventions exist. Individual Placement and Support (IPS) is an evidence-based work rehabilitation model originally developed to help people with severe mental illness obtain and maintain employment. The effectiveness of IPS for patients with severe mental illness is well documented, but the model has never before been tested for patients with chronic pain. The aim of the IPS in Pain trial is to investigate the effectiveness of IPS as an integrated part of the interdisciplinary treatment for patients with chronic pain in a hospital outpatient clinic. The study is a randomized controlled trial comparing pain treatment with integrated IPS to treatment as usual in unemployed patients suffering from various chronic pain conditions. The primary outcome of the study is labor market participation during 12 months after enrollment, and secondary outcomes include physical and mental health and well-being, collected at baseline, 6, and 12 months. Finally, there will be an additional long-term follow-up for the primary outcome, which will be collected through a brief phone interview at 24 months. The IPS in Pain trial will be the first report of the effectiveness of the IPS model of supported employment applied in an outpatient setting for chronic pain patients. It will thus provide important information about the effectiveness of repurposing IPS to a new patient group in great need of job support. Clinicaltrials.gov: NCT02697656 . Registered January 15th, 2016.

  18. EFFECTS AND MECHANISMS OF A NEW MULTIVITAMIN ON CHRONIC METABOLIC SYNDROMES AND AGING

    PubMed Central

    Wu, Su-xi; Jiang, Xuewei; Liu, Yu-ying; Chen, Lin-feng; Tao, Jun

    2017-01-01

    Background: Increased occurrence of chronic syndromes has prompted researchers to investigate and develop drugs and methods for controlling chronic syndromes with a view to improve human health and reduce early aging. Material and methods: Human trials: After the allotted multivitamin pills or placebo pills had been taken for a stipulated period of about 2 months, the volunteers filled out feedback forms on curative effects of the pills in line with the health examination reports. The effects of the multivitamin on various symptoms or diseases and dysfunctions of the chronic metabolic syndromes were noted and evaluated based on the information provided in forms. Animal experiments: Mouse aging model induced by D-galactose were administered the multivitamin by oral gavage every morning. At the end of the sixth week, activity or content of the components associated with ageing and anti-aging in the brain and liver of the aging mice were determined to investigate the mechanisms of the new multivitamin on chronic metabolic syndromes and aging. Results: We found that multivitamin can eliminate or attenuate 38 types of symptoms or dysfunctions of the investigated metabolic syndromes; and that it has both preventive and curative/adjunctive therapeutic effects on the metabolic syndromes. The effects of this multivitamin on components associated with aging and anti-aging were significantly decreased - malondialdehyde content and monoamine oxidase activity but significantly increased activity of superoxide dismutase and glutathione peroxidase. This multivitamin has significant anti-aging effects. Conclusion: Supplementing with this multivitamin can prevent and provide treatment/adjunctive therapy for these chronic metabolic syndromes and delay the aging process. List of Abbreviations BW body weight; Cu/Zn-SOD, cuprum/zinc-superoxide dismutase MAO monoamine oxidase MDA malondialdehyde; Mn-SOD, manganese-superoxide dismutase; T-SOD, total superoxide dismutase; TP, total protein PMID:28331914

  19. EFFECTS AND MECHANISMS OF A NEW MULTIVITAMIN ON CHRONIC METABOLIC SYNDROMES AND AGING.

    PubMed

    Wu, Su-Xi; Jiang, Xuewei; Liu, Yu-Ying; Chen, Lin-Feng; Tao, Jun

    2017-01-01

    Increased occurrence of chronic syndromes has prompted researchers to investigate and develop drugs and methods for controlling chronic syndromes with a view to improve human health and reduce early aging. Human trials: After the allotted multivitamin pills or placebo pills had been taken for a stipulated period of about 2 months, the volunteers filled out feedback forms on curative effects of the pills in line with the health examination reports. The effects of the multivitamin on various symptoms or diseases and dysfunctions of the chronic metabolic syndromes were noted and evaluated based on the information provided in forms. Animal experiments: Mouse aging model induced by D-galactose were administered the multivitamin by oral gavage every morning. At the end of the sixth week, activity or content of the components associated with ageing and anti-aging in the brain and liver of the aging mice were determined to investigate the mechanisms of the new multivitamin on chronic metabolic syndromes and aging. We found that multivitamin can eliminate or attenuate 38 types of symptoms or dysfunctions of the investigated metabolic syndromes; and that it has both preventive and curative/adjunctive therapeutic effects on the metabolic syndromes. The effects of this multivitamin on components associated with aging and anti-aging were significantly decreased - malondialdehyde content and monoamine oxidase activity but significantly increased activity of superoxide dismutase and glutathione peroxidase. This multivitamin has significant anti-aging effects. Supplementing with this multivitamin can prevent and provide treatment/adjunctive therapy for these chronic metabolic syndromes and delay the aging process. List of AbbreviationsBWbody weight; Cu/Zn-SOD, cuprum/zinc-superoxide dismutaseMAOmonoamine oxidaseMDAmalondialdehyde; Mn-SOD, manganese-superoxide dismutase; T-SOD, total superoxide dismutase; TP, total protein.

  20. The effects of reduced dopamine transporter function and chronic lithium on motivation, probabilistic learning, and neurochemistry in mice: Modeling bipolar mania.

    PubMed

    Milienne-Petiot, Morgane; Kesby, James P; Graves, Mary; van Enkhuizen, Jordy; Semenova, Svetlana; Minassian, Arpi; Markou, Athina; Geyer, Mark A; Young, Jared W

    2017-02-01

    Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses. The effects of reducing dopamine transporter (DAT) functioning via genetic (knockdown vs. wild-type littermates), or pharmacological (GBR12909- vs. vehicle-treated C57BL/6J mice) means were assessed in the probabilistic reversal learning task (PRLT), and progressive ratio breakpoint (PRB) test, during either water or chronic lithium treatment. These tasks quantify reward learning and effortful motivation, respectively. Neurochemistry was performed on brain samples of DAT mutants ± chronic lithium using high performance liquid chromatography. Reduced DAT functioning increased reversals in the PRLT, an effect partially attenuated by chronic lithium. Chronic lithium alone slowed PRLT acquisition. Reduced DAT functioning increased motivation (PRB), an effect attenuated by lithium in GBR12909-treated mice. Neurochemical analyses revealed that DAT knockdown mice exhibited elevated homovanillic acid levels, but that lithium had no effect on these elevated levels. Reducing DAT functioning recreates many aspects of BD mania including hypermotivation and improved reversal learning (switching), as well as elevated homovanillic acid levels. Chronic lithium only exerted main effects, impairing learning and elevating norepinephrine and serotonin levels of mice, not specifically treating the underlying mechanisms identified in these models. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Hepatitis C Virus and Antiviral Drug Resistance.

    PubMed

    Kim, Seungtaek; Han, Kwang-Hyub; Ahn, Sang Hoon

    2016-11-15

    Since its discovery in 1989, hepatitis C virus (HCV) has been intensively investigated to understand its biology and develop effective antiviral therapies. The efforts of the previous 25 years have resulted in a better understanding of the virus, and this was facilitated by the development of in vitro cell culture systems for HCV replication. Antiviral treatments and sustained virological responses have also improved from the early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C, similar to other chronic viral infections, and retreatment options following treatment failure have become important questions. Despite the clinical challenges in the management of chronic hepatitis C, substantial progress has been made in understanding HCV, which may facilitate the investigation of other closely related flaviviruses and lead to the development of antiviral agents against these human pathogens.

  2. Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

    PubMed Central

    Daiber, Andreas; Oelze, Matthias; Wenzel, Philip; Bollmann, Franziska; Pautz, Andrea; Kleinert, Hartmut

    2012-01-01

    Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/– mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy. PMID:22506100

  3. [Star fruit (Averrhoa carambola) toxic encephalopathy].

    PubMed

    Signaté, A; Olindo, S; Chausson, N; Cassinoto, C; Edimo Nana, M; Saint Vil, M; Cabre, P; Smadja, D

    2009-03-01

    Ingestion of star fruit (Averrhoa carambola) can induce severe intoxication in subjects with chronic renal failure. Oxalate plays a key role in the neurotoxicity of star fruit. We report the cases of two patients with unknown chronic renal insufficiency who developed severe encephalopathy after ingestion of star fruit. The two patients developed intractable hiccups, vomiting, impaired consciousness and status epilepticus. Diffusion-weighted MR imaging showed cortical and thalamic hyperintense lesions related to epileptic status. They improved after being submitted to continuous hemofiltration which constitutes the most effective treatment during the acute phase.

  4. Chronic aspiration of gastric fluid induces the development of obliterative bronchiolitis in rat lung transplants.

    PubMed

    Li, B; Hartwig, M G; Appel, J Z; Bush, E L; Balsara, K R; Holzknecht, Z E; Collins, B H; Howell, D N; Parker, W; Lin, S S; Davis, R D

    2008-08-01

    Long-term survival of a pulmonary allograft is currently hampered by obliterative bronchiolitis (OB), a form of chronic rejection that is unique to lung transplantation. While tracheobronchial aspiration from gastroesophageal reflux disease (GERD) has clinically been associated with OB, no experimental model exists to investigate this problem. Using a WKY-to-F344 rat orthotopic left lung transplant model, the effects of chronic aspiration on pulmonary allograft were evaluated. Recipients received cyclosporine with or without 8 weekly aspirations of gastric fluid into the allograft. Six (66.7%) of 9 allografts with aspiration demonstrated bronchioles with surrounding monocytic infiltrates, fibrosis and loss of normal lumen anatomy, consistent with the development of OB. In contrast, none of the allografts without aspiration (n = 10) demonstrated these findings (p = 0.002). Of the grafts examined grossly, 83% of the allografts with chronic aspiration but only 20% without aspiration appeared consolidated (p = 0.013). Aspiration was associated with increased levels of IL-1 alpha, IL-1 beta, IL-6, IL-10, TNF-alpha and TGF-beta in BAL and of IL-1 alpha, IL-4 and GM-CSF in serum. This study provides experimental evidence linking chronic aspiration to the development of OB and suggests that strategies aimed at preventing aspiration-related injuries might improve outcomes in clinical lung transplantation.

  5. [New welding processes and health effects of welding].

    PubMed

    La Vecchia, G Marina; Maestrelli, Piero

    2011-01-01

    This paper describes some of the recent developments in the control technology to enhance capability of Pulse Gas Metal Arc Welding. Friction Stir Welding (FSW) processing has been also considered. FSW is a new solid-state joining technique. Heat generated by friction at the rotating tool softens the material being welded. FSW can be considered a green and energy-efficient technique without deleterious fumes, gas, radiation, and noise. Application of new welding processes is limited and studies on health effects in exposed workers are lacking. Acute and chronic health effects of conventional welding have been described. Metal fume fever and cross-shift decline of lung function are the main acute respiratory effects. Skin and eyes may be affected by heat, electricity and UV radiations. Chronic effects on respiratory system include chronic bronchitis, a benign pneumoconiosis (siderosis), asthma, and a possible increase in the incidence of lung cancer. Pulmonary infections are increased in terms of severity, duration, and frequency among welders.

  6. Protective Effect of Self-Compassion to Emotional Response among Students with Chronic Academic Stress

    PubMed Central

    Zhang, Yonghong; Luo, Xi; Che, Xianwei; Duan, Wenjie

    2016-01-01

    The literature has shown that self-compassion is a protective factor of an individual’s emotional response to chronic stress. However, this stress-buffering effect has not been completely analyzed in individuals who report significantly high academic stress. The present study explored the role of self-compassion in a group of undergraduate students who experience chronic academic stress. A total of 208 undergraduate students who were preparing for the Postgraduate Entrance Examination (PEE) were recruited and completed the Self-Compassion Scale, Adolescent Self-Rating Life Event Check List, and Positive and Negative Affect Schedule. Differences analysis confirmed that the participants reported significantly higher academic stress than their peers who were not preparing for PEE. Self-compassion positively related to positive affect but negatively related to negative affect and learning stress. Further analysis showed that self-compassion negatively mediated the relationship between chronic academic stress and negative affect. Findings imply that self-compassion-centered interventions can be developed in the educational context to assist students cope with chronic academic stress. PMID:27920736

  7. Regenerative toxicology: the role of stem cells in the development of chronic toxicities.

    PubMed

    Canovas-Jorda, David; Louisse, Jochem; Pistollato, Francesca; Zagoura, Dimitra; Bremer, Susanne

    2014-01-01

    Human stem cell lines and their derivatives, as alternatives to the use of animal cells or cancer cell lines, have been widely discussed as cellular models in predictive toxicology. However, the role of stem cells in the development of long-term toxicities and carcinogenesis has not received great attention so far, despite growing evidence indicating the relationship of stem cell damage to adverse effects later in life. However, testing this in vitro is a scientific/technical challenge in particular due to the complex interplay of factors existing under physiological conditions. Current major research programs in stem cell toxicity are not aiming to demonstrate that stem cells can be targeted by toxicants. Therefore, this knowledge gap needs to be addressed in additional research activities developing technical solutions and defining appropriate experimental designs. The current review describes selected examples of the role of stem cells in the development of long-term toxicities in the brain, heart or liver and in the development of cancer. The presented examples illustrate the need to analyze the contribution of stem cells to chronic toxicity in order to make a final conclusion whether stem cell toxicities are an underestimated risk in mechanism-based safety assessments. This requires the development of predictive in vitro models allowing the assessment of adverse effects to stem cells on chronic toxicity and carcinogenicity.

  8. Chronic disease management: improving care for people with osteoarthritis.

    PubMed

    Brand, Caroline A; Ackerman, Ilana N; Tropea, Joanne

    2014-02-01

    Chronic disease management (CDM) service models are being developed for many conditions; however, there is limited evidence to support their effectiveness in osteoarthritis (OA). A systematic review was undertaken to examine effectiveness, cost effectiveness and barriers to the use of osteoarthritis-chronic disease management (OA-CDM) service models. Thirteen eligible studies (eight randomised controlled trial (RCTs)) were identified. The majority focussed on delivery system design (n = 9) and/or providing self-management support (SMS) (n = 8). Overall, reported model effectiveness varied, and where positive impacts on process or health outcomes were observed, they were of small to moderate effect. There was no information about cost effectiveness. There is some evidence to support the use of collaborative care/multidisciplinary case management models in primary and community care and evidence-based pathways/standardisation of care in hospital settings. Multiple barriers were identified. Future research should focus on identifying the effective components of multi-faceted interventions and evaluating cost-effectiveness to support clinical and policy decision-making. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. [Turpentine baths in rehabilitation of patients with chronic obstructive pulmonary disease].

    PubMed

    Aĭrapetova, N S; Polikanova, E B; Davydova, O B; Gosn, L D; Kulikova, O V; Ksenofontova, I V; Nikoda, N V; Rassulova, M A; Nitchenko, O V; Siziakova, L A; Doronina, Iu V; Derevnina, N A

    2007-01-01

    We have investigated effects of turpentine baths with white emultion, yellow solution and mixed on the course of inflammation, immunocompetent system, external respiration function, pulmonary cardiohemodynamics, physical performance in patients with chronic obstructive pulmonary disease. We developed differential indications for each bath variant depending on the features of a clinical picture of the disease, comorbid pathology and revealed contraindications to their administration.

  10. Effect of an Educational Program on Adherence to Therapeutic Regimen among Chronic Kidney Disease Stage5 (CKD5) Patients under Maintenance Hemodialysis

    ERIC Educational Resources Information Center

    Deif, Hala I. Abo; Elsawi, Khiria; Selim, Mohga; NasrAllah, Mohamed M.

    2015-01-01

    The burden of chronic disease on health care services worldwide is growing and the increased development of educational interventions which help patients to better manage their conditions is evident internationally. It has been recognized that poor adherence can be a serious risk to the health and wellbeing of patients. Adherence to fluid…

  11. Targeting Acceptance, Mindfulness, and Values-Based Action in Chronic Pain: Findings of Two Preliminary Trials of an Outpatient Group-Based Intervention

    ERIC Educational Resources Information Center

    Vowles, Kevin E.; Wetherell, Julie Loebach; Sorrell, John T.

    2009-01-01

    Cognitive behavior therapy (CBT) for chronic pain is effective, although a number of issues in need of clarification remain, including the processes by which CBT works, the role of cognitive changes in the achievement of outcomes, and the formulation of a coherent theoretical model. Recent developments in psychology have attempted to address these…

  12. The importance of illness duration, age at diagnosis and the year of diagnosis for labour participation chances of people with chronic illness: results of a nationwide panel-study in The Netherlands.

    PubMed

    Rijken, Mieke; Spreeuwenberg, Peter; Schippers, Joop; Groenewegen, Peter P

    2013-09-04

    Compared to participation rates among general populations, participation of people with chronic illness in the labour market lags behind. This is undesirable, both from the perspective of individuals' well-being as from a macro-economic perspective for western countries where concerns exist about labour supply and sustainability of social security in the near future. To help develop successful policy measures to prevent early drop-out and support reintegration, we aimed to gain insight into the role of three age related characteristics that may relate to labour participation chances of people with chronic illness: the duration of their illness, how old they were when the chronic disease was diagnosed and the historical year in which the diagnosis was established. We analyzed data of one (first) measurement of several cohorts of people diagnosed with a somatic chronic disease, who (had) participated in the Dutch 'National Panel of people with Chronic illness or Disability' since 1998 (N = 4634 in total). Multi-level logistic regression analyses were conducted to estimate random effects of the age at diagnosis and the year of diagnosis and fixed effects of illness duration on labour participation, while correcting for the effects of socio-demographic and disease characteristics and socio-economic indicators. A significant part of the variation in labour participation among people with chronic illness relates to the age they had when they were diagnosed. Furthermore, a longer illness duration is significantly associated with a lower chance of being economically active. This is more the case for men than for women. Labour participation of cancer survivors depends on the phase of the illness they find themselves in. No evidence was found that the year in which the diagnosis was established matters for employment chances later in life. Age at diagnosis and illness duration relate to chronically ill people's chances to participate in the labour market, but how and how strong they relate to labour participation depend on gender and the type of chronic disease at stake. Prospective studies are needed to assess illness trajectories of specific diagnostic groups along with the development of their school and work careers.

  13. The importance of illness duration, age at diagnosis and the year of diagnosis for labour participation chances of people with chronic illness: results of a nationwide panel-study in the Netherlands

    PubMed Central

    2013-01-01

    Background Compared to participation rates among general populations, participation of people with chronic illness in the labour market lags behind. This is undesirable, both from the perspective of individuals’ well-being as from a macro-economic perspective for western countries where concerns exist about labour supply and sustainability of social security in the near future. To help develop successful policy measures to prevent early drop-out and support reintegration, we aimed to gain insight into the role of three age related characteristics that may relate to labour participation chances of people with chronic illness: the duration of their illness, how old they were when the chronic disease was diagnosed and the historical year in which the diagnosis was established. Methods We analyzed data of one (first) measurement of several cohorts of people diagnosed with a somatic chronic disease, who (had) participated in the Dutch ‘National Panel of people with Chronic illness or Disability’ since 1998 (N = 4634 in total). Multi-level logistic regression analyses were conducted to estimate random effects of the age at diagnosis and the year of diagnosis and fixed effects of illness duration on labour participation, while correcting for the effects of socio-demographic and disease characteristics and socio-economic indicators. Results A significant part of the variation in labour participation among people with chronic illness relates to the age they had when they were diagnosed. Furthermore, a longer illness duration is significantly associated with a lower chance of being economically active. This is more the case for men than for women. Labour participation of cancer survivors depends on the phase of the illness they find themselves in. No evidence was found that the year in which the diagnosis was established matters for employment chances later in life. Conclusion Age at diagnosis and illness duration relate to chronically ill people’s chances to participate in the labour market, but how and how strong they relate to labour participation depend on gender and the type of chronic disease at stake. Prospective studies are needed to assess illness trajectories of specific diagnostic groups along with the development of their school and work careers. PMID:24007362

  14. PSCs and GLP-1R: occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist

    PubMed Central

    Nakamura, Taichi; Ito, Tetsuhide; Uchida, Masahiko; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Jensen, Robert T.; Takayanagi, Ryoichi

    2013-01-01

    Background and Aims There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term GLP-1 analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells is well studied, however there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can play an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute/chronic pancreatitis, and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. Methods GLP-1R expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP1R expression and effects of GLP-1 analog on activated PSCs was examined with realtime PCR, MTS assays and Western Blotting. Results In normal pancreas, pancreatic β cells expressed GLP-1R, with only low expression in acinar cells, whereas in acute or chronic pancreatitis, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the ERK pathway mediated the PSCs proliferation. Conclusions GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in acute/chronic pancreatitis. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation/chronic activation of PSCs, which may lead to important effects in the pancreas. PMID:24217090

  15. A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice.

    PubMed

    Long, Leonora E; Chesworth, Rose; Huang, Xu-Feng; McGregor, Iain S; Arnold, Jonathon C; Karl, Tim

    2010-08-01

    Cannabis contains over 70 unique compounds and its abuse is linked to an increased risk of developing schizophrenia. The behavioural profiles of the psychotropic cannabis constituent Delta9-tetrahydrocannabinol (Delta9-THC) and the non-psychotomimetic constituent cannabidiol (CBD) were investigated with a battery of behavioural tests relevant to anxiety and positive, negative and cognitive symptoms of schizophrenia. Male adult C57BL/6JArc mice were given 21 daily intraperitoneal injections of vehicle, Delta9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Delta9-THC produced the classic cannabinoid CB1 receptor-mediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, Delta9-THC (10 mg/kg) produced locomotor-independent anxiogenic effects in the open-field and light-dark tests. Chronic CBD produced moderate anxiolytic-like effects in the open-field test at 50 mg/kg and in the light-dark test at a low dose (1 mg/kg). Acute and chronic Delta9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with Delta9-THC (0.3, 3 and 10 mg/kg) or CBD (1, 5 and 50 mg/kg) and by chronic CBD (1 mg/kg). Chronic CBD (50 mg/kg) attenuated dexamphetamine (5 mg/kg)-induced hyperlocomotion, suggesting an antipsychotic-like action for this cannabinoid. Chronic Delta9-THC decreased locomotor activity before and after dexamphetamine administration suggesting functional antagonism of the locomotor stimulant effect. These data provide the first evidence of anxiolytic- and antipsychotic-like effects of chronic but not acute CBD in C57BL/6JArc mice, extending findings from acute studies in other inbred mouse strains and rats.

  16. Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna.

    PubMed

    Haeba, Maher H; Hilscherová, Klára; Mazurová, Edita; Bláha, Ludek

    2008-05-01

    Pollution-induced endocrine disruption in vertebrates and invertebrates is a worldwide environmental problem, but relatively little is known about effects of endocrine disrupting compounds (EDCs) in planktonic crustaceans (including Daphnia magna). Aims of the present study were to investigate acute 48 h toxicity and sub-chronic (4-6 days) and chronic (21 days) effects of selected EDCs in D. magna. We have investigated both traditional endpoints as well as other parameters such as sex determination, maturation, molting or embryogenesis in order to evaluate the sensitivity and possible use of these endpoints in ecological risk assessment. We have studied effects of four model EDCs (vinclozolin, flutamide, ketoconazole and dicofol) on D. magna using (i) an acute 48 h immobilization assay, (ii) a sub-chronic, 4-6 day assay evaluating development and the sex ratio of neonates, and (iii) a chronic, 21 day assay studying number of neonates, sex of neonates, molting frequency, day of maturation and the growth of maternal organisms. Acute EC50 values in the 48 h immobilization test were as follows (mg/L): dicofol 0.2, ketoconazole 1.5, flutamide 2.7, vinclozolin >3. Short-term, 4-6 day assays with sublethal concentrations showed that the sex ratio in Daphnia was modulated by vinclozolin (decreased number of neonate males at 1 mg/L) and dicofol (increase in males at 0.1 mg/L). Flutamide (up to 1 mg/L) had no effect on the sex of neonates, but inhibited embryonic development at certain stages during chronic assay, resulting in abortions. Ketoconazole had no significant effects on the studied processes up to 1 mg/L. Sex ratio modulations by some chemicals (vinclozolin and dicofol) corresponded to the known action of these compounds in vertebrates (i.e. anti-androgenicity and anti-oestrogenicity, respectively). Our study revealed that some chemicals known to affect steroid-regulated processes in vertebrates can also affect sublethal endpoints (e.g. embryonic sex determination and/or reproduction) in invertebrates such as D. magna. A series of model vertebrate endocrine disrupters affected various sub-chronic and chronic parameters in D. magna including several endpoints that have not been previously studied in detail (such as sex determination in neonates, embryogenesis, molting and maturation). Evaluations of traditional reproduction parameters (obtained from the 21 day chronic assay). as well as the results from a rapid, 4-6 day, sub-chronic assay provide complementary information on non-lethal effects of suspected organic endocrine disrupters. It seems that there are analogies between vertebrates and invertebrates in toxicity mechanisms and in vivo effects of endocrine disruptors. However, general physiological status of organisms may also indirectly affect endpoints that are traditionally considered 'hormone regulated' (especially at higher effective concentrations as observed in this study) and these factors should be carefully considered. Further research of D. magna physiology and comparative studies with various EDCs will help to understand mechanisms of action as well as ecological risks of EDCs in the environment.

  17. New developments in endoscopic treatment of chronic pancreatitis.

    PubMed

    Didden, P; Bruno, M; Poley, J W

    2012-12-01

    The aim of endoscopic therapy of chronic pancreatitis (CP) is to treat pain by draining the pancreatic duct or managing loco-regional complications. Recent decennia were characterized by continuous improvement of endoscopic techniques and devices, resulting in a better clinical outcome. Novel developments now also provide the opportunity to endoscopically treat refractory CP-related complications. Especially suboptimal surgical candidates could potentially benefit from these new developments, consequently avoiding invasive surgery. The use of fully covered self-expandable metal stents (SEMS) has been explored in pancreatic and CP-related biliary duct strictures, resistant to conventional treatment with plastic endoprotheses. Furthermore, endosonography-guided transmural drainage of the main pancreatic duct via duct-gastrostomy is an alternative treatment option in selected cases. Pancreatic pseudocysts represent an excellent indication for endoscopic therapy with some recent case series demonstrating effective drainage with the use of a fully covered SEMS. Although results of these new endoscopic developments are promising, high quality randomized trials are required to determine their definite role in the management of chronic pancreatitis.

  18. Health technologies for the improvement of chronic disease management: a review of the Medical Advisory Secretariat evidence-based analyses between 2006 and 2011.

    PubMed

    Nikitovic, M; Brener, S

    2013-01-01

    As part of ongoing efforts to improve the Ontario health care system, a mega-analysis examining the optimization of chronic disease management in the community was conducted by Evidence Development and Standards, Health Quality Ontario (previously known as the Medical Advisory Secretariat [MAS]). The purpose of this report was to identify health technologies previously evaluated by MAS that may be leveraged in efforts to optimize chronic disease management in the community. The Ontario Health Technology Assessment Series and field evaluations conducted by MAS and its partners between January 1, 2006, and December 31, 2011. Technologies related to at least 1 of 7 disease areas of interest (type 2 diabetes, coronary artery disease, atrial fibrillation, chronic obstructive pulmonary disease, congestive heart failure, stroke, and chronic wounds) or that may greatly impact health services utilization were reviewed. Only technologies with a moderate to high quality of evidence and associated with a clinically or statistically significant improvement in disease management were included. Technologies related to other topics in the mega-analysis on chronic disease management were excluded. Evidence-based analyses were reviewed, and outcomes of interest were extracted. Outcomes of interest included hospital utilization, mortality, health-related quality of life, disease-specific measures, and economic analysis measures. Eleven analyses were included and summarized. Technologies fell into 3 categories: those with evidence for the cure of chronic disease, those with evidence for the prevention of chronic disease, and those with evidence for the management of chronic disease. The impact on patient outcomes and hospitalization rates of new health technologies in chronic disease management is often overlooked. This analysis demonstrates that health technologies can reduce the burden of illness; improve patient outcomes; reduce resource utilization intensity; be cost-effective; and be a viable contributing factor to chronic disease management in the community. People with chronic diseases rely on the health care system to help manage their illness. Hospital use can be costly, so community-based alternatives are often preferred. Research published in the Ontario Health Technology Assessment Series between 2006 and 2011 was reviewed to identify health technologies that have been effective or cost-effective in helping to manage chronic disease in the community. All technologies identified led to better patient outcomes and less use of health services. Most were also cost-effective. Two technologies that can cure chronic disease and 1 that can prevent chronic disease were found. Eight technologies that can help manage chronic disease were also found. Health technologies should be considered an important part of chronic disease management in the community.

  19. Health Technologies for the Improvement of Chronic Disease Management

    PubMed Central

    Nikitovic, M; Brener, S

    2013-01-01

    Background As part of ongoing efforts to improve the Ontario health care system, a mega-analysis examining the optimization of chronic disease management in the community was conducted by Evidence Development and Standards, Health Quality Ontario (previously known as the Medical Advisory Secretariat [MAS]). Objective The purpose of this report was to identify health technologies previously evaluated by MAS that may be leveraged in efforts to optimize chronic disease management in the community. Data Sources The Ontario Health Technology Assessment Series and field evaluations conducted by MAS and its partners between January 1, 2006, and December 31, 2011. Review Methods Technologies related to at least 1 of 7 disease areas of interest (type 2 diabetes, coronary artery disease, atrial fibrillation, chronic obstructive pulmonary disease, congestive heart failure, stroke, and chronic wounds) or that may greatly impact health services utilization were reviewed. Only technologies with a moderate to high quality of evidence and associated with a clinically or statistically significant improvement in disease management were included. Technologies related to other topics in the mega-analysis on chronic disease management were excluded. Evidence-based analyses were reviewed, and outcomes of interest were extracted. Outcomes of interest included hospital utilization, mortality, health-related quality of life, disease-specific measures, and economic analysis measures. Results Eleven analyses were included and summarized. Technologies fell into 3 categories: those with evidence for the cure of chronic disease, those with evidence for the prevention of chronic disease, and those with evidence for the management of chronic disease. Conclusions The impact on patient outcomes and hospitalization rates of new health technologies in chronic disease management is often overlooked. This analysis demonstrates that health technologies can reduce the burden of illness; improve patient outcomes; reduce resource utilization intensity; be cost-effective; and be a viable contributing factor to chronic disease management in the community. Plain Language Summary People with chronic diseases rely on the health care system to help manage their illness. Hospital use can be costly, so community-based alternatives are often preferred. Research published in the Ontario Health Technology Assessment Series between 2006 and 2011 was reviewed to identify health technologies that have been effective or cost-effective in helping to manage chronic disease in the community. All technologies identified led to better patient outcomes and less use of health services. Most were also cost-effective. Two technologies that can cure chronic disease and 1 that can prevent chronic disease were found. Eight technologies that can help manage chronic disease were also found. Health technologies should be considered an important part of chronic disease management in the community. PMID:24228075

  20. Effectiveness of gratitude disposition promotion program on depression and quality of life of chronic schizophrenic patients

    PubMed Central

    Jung, Miran; Han, Kuemsun

    2017-01-01

    Context: Gratitude intervention is expectedly an effective intervention to reduce depression and improve the quality of life in schizophrenic patients, but there is a lack of literature on it. Aims: We attempted to develop and test the effectiveness of the gratitude disposition promotion program for chronic schizophrenic patients in Korea. Settings and Design: Nonequivalent control group pre- and post-test design was used in two mental health centers located at Gyeonggi-do in South Korea. Materials and Methods: This paper was a quasi-experimental study and the participants who took part in the gratitude disposition promotion program were 17 of experimental group and 15 of control group. Gratitude disposition (the short gratitude, resentment, and appreciation test), depression (Beck Depression Inventory), and quality of life (developed by Kook) of chronic schizophrenic patients were measured before and after an intervention, as compared to the control. Statistical Analysis: Chi-square test, Fisher's exact test, and t-test were performed for prehomogeneity testing for variables related to the general characteristics. Testing for the effectiveness of gratitude disposition promotion program and hypothesis testing for its effect on depression and quality of life were by ANCOVA and t-test, as verified to significance level of P < 0.05. Results: The participants who received the gratitude disposition promotion program showed significant improvements in gratitude disposition (F = 18.740, P < 0.0001) and in quality of life (F = 9.800, P = 0.004), but no significant difference in depression (F = 3.870, P = 0.059). Conclusions: The gratitude disposition promotion program was an effective clinical intervention program for enhancing gratitude disposition and quality of life of chronic schizophrenic patients in community. PMID:28827866

  1. The effects of chronic intraperitoneal administration of the GABA B receptor agonist baclofen on food intake in rats.

    PubMed

    Patel, Sunit M; Ebenezer, Ivor S

    2008-09-28

    This study was undertaken to examine the effects of repeated administration of the GABA(B) receptor agonist baclofen on food intake in male Wistar rats. In the 1st Experiment, the effects of daily administration of physiological saline and baclofen (2 mg/kg, i.p.) for 27 days were investigated on food intake and body weight in non-deprived rats (n=6 in each group). Baclofen significantly (P<0.05) increased cumulative food intake each day over the treatment period during the 60 min measurement period following administration. Tolerance did not develop to the short-term hyperphagic effect of baclofen over the course of the experiment. In addition, treatment with baclofen did not alter body weight of the animals over the 27 day treatment period when compared with the saline control rats. In the 2nd Experiment, the effects of acute and chronic administration of baclofen (2 mg/kg) were investigated on 24 h food intake in rats. The rats were injected daily for 21 days with either saline (n=6) or baclofen (n=6). Food intake was measured in 30 min time bins for 24 h on treatment Days 1, 12 and 21 following injection. The results showed that while baclofen produced short-term increases in food consumption following injection on treatment Days 1, 12 and 21, the daily (24 h) food intake of the animals was not significantly different from those of control rats. Thus, these data reveal that while chronic administration of baclofen (2 mg/kg) produces short-term increases in feeding without the development of tolerance, daily (24 h) food consumption is not affected. These findings are consistent with the observation that chronic administration of baclofen (2 mg/kg) had no effect on the body weight of these animals.

  2. Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models

    PubMed Central

    Willis, Sarah; Stoll, James; Sweetman, Lawrence; Borges, Karin

    2010-01-01

    We hypothesized that in epileptic brains citric acid cycle intermediate levels may be deficient leading to hyperexcitability. Anaplerosis is the metabolic refilling of deficient metabolites. Our goal was to determine the anticonvulsant effects of feeding triheptanoin, the triglyceride of anaplerotic heptanoate. CF1 mice were fed 0-35% calories from triheptanoin. Body weights and dietary intake were similar in mice fed triheptanoin vs. standard diet. Triheptanoin feeding increased blood propionyl-carnitine levels, signifying its metabolism. 35%, but not 20%, triheptanoin delayed development of corneal kindled seizures. After pilocarpine-induced status epilepticus (SE), triheptanoin feeding increased the pentylenetetrazole tonic seizure threshold during the chronically epileptic stage. Mice in the chronically epileptic stage showed various changes in brain metabolite levels, including a reduction in malate. Triheptanoin feeding largely restored a reduction in propionyl-CoA levels and increased methylmalonyl-CoA levels in SE mice. In summary, triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. The mechanisms of triheptanoin's effects and its efficacy in humans suffering from epilepsy remain to be determined. PMID:20691264

  3. [The application of laser therapy for the medical rehabilitation of the children presenting with chronic osteomyelitis].

    PubMed

    Trunova, O V; Mashkov, A E; Khan, M A; Prikuls, V F; Nazarenko, N N; Supova, M V; Smirnova, S N; Larionov, K S

    2015-01-01

    The objective of the present study was to develop a scientifically sound rationale for the application of infrared laser radiation (IRLR) either separately or in the combination with fluctuation magnetic therapy in the medical rehabilitation of the children presenting with chronic hematogenous osteomyelitis. Another objective was to evaluate the clinical effectiveness of this therapeutic modality. Two achieve these goals, the clinical observations and special research studies were conducted in two directions with the participation of 95 patients at the age varying from 1 to 15 years. The study has demonstrated the effectiveness of the inclusion of IRLR in the medical rehabilitation program for the children with chronic hematogenous osteomyelitis in different periods of the disease. It was shown that the transcutaneous infrared irradiation of the affected area during the exacerbation of chronic osteomyelitis had a well apparent immunostimulatory effect and reduced the activity of the inflammatory process. The application of IRLR in combination with fluctuation magnetic therapy during the period of partial remission, had a more pronounced influence on the microcirculation and stimulated the regenerative and trophic processes.

  4. Mechanisms by Which Dehydration May Lead to Chronic Kidney Disease.

    PubMed

    Roncal-Jimenez, C; Lanaspa, M A; Jensen, T; Sanchez-Lozada, L G; Johnson, R J

    2015-01-01

    Dehydration, a condition that characterizes excessive loss of body water, is well known to be associated with acute renal dysfunction; however, it has largely been considered reversible and to be associated with no long-term effects on the kidney. Recently, an epidemic of chronic kidney disease has emerged in Central America in which the major risk factor seems to be recurrent heat-associated dehydration. This has led to studies investigating whether recurrent dehydration may lead to permanent kidney damage. Three major potential mechanisms have been identified, including the effects of vasopressin on the kidney, the activation of the aldose reductase-fructokinase pathway, and the effects of chronic hyperuricemia. The discovery of these pathways has also led to the recognition that mild dehydration may be a risk factor in progression of all types of chronic kidney diseases. Furthermore, there is some evidence that increasing hydration, particularly with water, may actually prevent CKD. Thus, a whole new area of investigation is developing that focuses on the role of water and osmolarity and their influence on kidney function and health. © 2015 S. Karger AG, Basel.

  5. Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats.

    PubMed

    Drion, Cato M; Borm, Lars E; Kooijman, Lieneke; Aronica, Eleonora; Wadman, Wytse J; Hartog, Aloysius F; van Vliet, Erwin A; Gorter, Jan A

    2016-05-01

    Inhibition of the mammalian target of rapamycin (mTOR) pathway has been suggested as a possible antiepileptogenic strategy in temporal lobe epilepsy (TLE). Here we aim to elucidate whether mTOR inhibition has antiepileptogenic and/or antiseizure effects using different treatment strategies in the electrogenic post-status epilepticus (SE) rat model. Effects of mTOR inhibitor rapamycin were tested using the following three treatment protocols: (1) "stop-treatment"-post-SE treatment (6 mg/kg/day) was discontinued after 3 weeks; rats were monitored for 5 more weeks thereafter, (2) "pretreatment"-rapamycin (3 mg/kg/day) was applied during 3 days preceding SE; and (3) "chronic phase-treatment"-5 days rapamycin treatment (3 mg/kg/day) in the chronic phase. We also tested curcumin, an alternative mTOR inhibitor with antiinflammatory and antioxidant effects, using chronic phase treatment. Seizures were continuously monitored using video-electroencephalography (EEG) recordings; mossy fiber sprouting, cell death, and inflammation were studied using immunohistochemistry. Blood was withdrawn regularly to assess rapamycin and curcumin levels with high performance liquid chromatography (HPLC). Stop-treatment led to a strong reduction of seizures during the 3-week treatment and a gradual reappearance of seizures during the following 5 weeks. Three days pretreatment did not prevent seizure development, whereas 5-day rapamycin treatment in the chronic phase reduced seizure frequency. Washout of rapamycin was slow and associated with a gradual reappearance of seizures. Rapamycin treatment (both 3 and 6 mg/kg) led to body growth reduction. Curcumin treatment did not reduce seizure frequency or lead to a decrease in body weight. The present study indicates that rapamycin cannot prevent epilepsy in the electrical stimulation post-SE rat model but has seizure-suppressing properties as long as rapamycin blood levels are sufficiently high. Oral curcumin treatment had no effect on chronic seizures, possibly because it did not reach the brain at adequate levels. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  6. Role of Alcohol Metabolism in Chronic Pancreatitis

    PubMed Central

    Vonlaufen, Alain; Wilson, Jeremy S.; Pirola, Romano C.; Apte, Minoti V.

    2007-01-01

    Alcohol abuse is the major cause of chronic inflammation of the pancreas (i.e., chronic pancreatitis). Although it has long been thought that alcoholic pancreatitis is a chronic disease from the outset, evidence is accumulating to indicate that chronic damage in the pancreas may result from repeated attacks of acute tissue inflammation and death (i.e., necroinflammation). Initially, research into the pathogenesis of alcoholic pancreatitis was related to ductular and sphincteric abnormalities. In recent years, the focus has shifted to the type of pancreas cell that produces digestive juices (i.e., acinar cell). Alcohol now is known to exert a number of toxic effects on acinar cells. Notably, acinar cells have been shown to metabolize alcohol (i.e., ethanol) via both oxidative (i.e., involving oxygen) and nonoxidative pathways. The isolation and study of pancreatic stellate cells (PSCs)—the key effectors in the development of connective tissue fibers (i.e., fibrogenesis) in the pancreas—has greatly enhanced our understanding of the pathogenesis of chronic pancreatitis. Pancreatic stellate cells become activated in response to ethanol and acetaldehyde, a toxic byproduct of alcohol metabolism. In addition, PSCs have the capacity to metabolize alcohol via alcohol dehydrogenase (the major oxidizing enzyme for ethanol). The fact that only a small percentage of heavy alcoholics develop chronic pancreatitis has led to the search for precipitating factors of the disease. Several studies have investigated whether variations in ethanol-metabolizing enzymes may be a trigger factor for chronic pancreatitis, but no definite relationship has been established so far. PMID:17718401

  7. Proactive and Early Aggressive Wound Management: A Shift in Strategy Developed by a Consensus Panel Examining the Current Science, Prevention, and Management of Acute and Chronic Wounds.

    PubMed

    Bohn, Gregory A; Schultz, Gregory S; Liden, Brock A; Desvigne, Michael N; Lullove, Eric J; Zilberman, Igor; Regan, Mary B; Ostler, Marta; Edwards, Karen; Arvanitis, Georgia M; Hartman, Jodi F

    2017-11-01

    Normal wound healing is accomplished through a series of well-coordinated, progressive events with overlapping phases. Chronic wounds are described as not progressing to healing or not being responsive to management in a timely manner. A consensus panel of multidisciplinary wound care professionals was assembled to (1) educate wound care practitioners by identifying key principles of the basic science of chronic wound pathophysiology, highlighting the impact of metalloproteinases and biofilms, as well as the role of the extracellular matrix; and (2) equip practitioners with a systematic strategy for the prevention and healing of acute injuries and chronic wounds based upon scientific evidence and the panel members' expertise. An algorithm is presented that represents a shift in strategy to proactive and early aggressive wound management. With proactive management, adjunct therapies are applied preemptively to acute injuries to reduce wound duration and risk of chronicity. For existing chronic wounds, early aggressive wound management is employed to break the pathophysiology cycle and drive wounds toward healing. Reducing bioburden through debridement and bioburden management and using collagen dressings to balance protease activity prior to the use of advanced modalities may enhance their effectiveness. This early aggressive wound management strategy is recommended for patients at high risk for chronic wound development at a minimum. In their own practices, the panel members apply this systematic strategy for all patients presenting with acute injuries or chronic wounds.

  8. Anti-stress effects of transcutaneous electrical nerve stimulation (TENS) on colonic motility in rats.

    PubMed

    Yoshimoto, Sazu; Babygirija, Reji; Dobner, Anthony; Ludwig, Kirk; Takahashi, Toku

    2012-05-01

    Disorders of colonic motility may contribute to symptoms in patients with irritable bowel syndrome (IBS), and stress is widely believed to play a major role in developing IBS. Stress increases corticotropin releasing factor (CRF) of the hypothalamus, resulting in acceleration of colonic transit in rodents. In contrast, hypothalamic oxytocin (OXT) has an anti-stress effect via inhibiting CRF expression and hypothalamic-pituitary-adrenal axis activity. Although transcutaneous electrical nerve stimulation (TENS) and acupuncture have been shown to have anti-stress effects, the mechanism of the beneficial effects remains unknown. We tested the hypothesis that TENS upregulates hypothalamic OXT expression resulting in reduced CRF expression and restoration of colonic dysmotility in response to chronic stress. Male SD rats received different types of stressors for seven consecutive days (chronic heterotypic stress). TENS was applied to the bilateral hind limbs every other day before stress loading. Another group of rats did not receive TENS treatment. TENS significantly attenuated accelerated colonic transit induced by chronic heterotypic stress, which was antagonized by a central injection of an OXT antagonist. Immunohistochemical study showed that TENS increased OXT expression and decreased CRF expression at the paraventricular nucleus (PVN) following chronic heterotypic stress. It is suggested that TENS upregulates hypothalamic OXT expression which acts as an anti-stressor agent and mediates restored colonic dysmotility following chronic stress. TENS may be useful to treat gastrointestinal symptoms associated with stress.

  9. Chronic toxicology of cannabis.

    PubMed

    Reece, Albert Stuart

    2009-07-01

    Cannabis is the most widely used illicit drug worldwide. As societies reconsider the legal status of cannabis, policy makers and clinicians require sound knowledge of the acute and chronic effects of cannabis. This review focuses on the latter. A systematic review of Medline, PubMed, PsychInfo, and Google Scholar using the search terms "cannabis," "marijuana," "marihuana," "toxicity," "complications," and "mechanisms" identified 5,198 papers. This list was screened by hand, and papers describing mechanisms and those published in more recent years were chosen preferentially for inclusion in this review. There is evidence of psychiatric, respiratory, cardiovascular, and bone toxicity associated with chronic cannabis use. Cannabis has now been implicated in the etiology of many major long-term psychiatric conditions including depression, anxiety, psychosis, bipolar disorder, and an amotivational state. Respiratory conditions linked with cannabis include reduced lung density, lung cysts, and chronic bronchitis. Cannabis has been linked in a dose-dependent manner with elevated rates of myocardial infarction and cardiac arrythmias. It is known to affect bone metabolism and also has teratogenic effects on the developing brain following perinatal exposure. Cannabis has been linked to cancers at eight sites, including children after in utero maternal exposure, and multiple molecular pathways to oncogenesis exist. Chronic cannabis use is associated with psychiatric, respiratory, cardiovascular, and bone effects. It also has oncogenic, teratogenic, and mutagenic effects all of which depend upon dose and duration of use.

  10. Measuring financial protection for health in families with chronic conditions in Rural China.

    PubMed

    Jiang, Chunhong; Ma, Jingdong; Zhang, Xiang; Luo, Wujin

    2012-11-16

    As the world's largest developing country, China has entered into the epidemiological phase characterized by high life expectancy and high morbidity and mortality from chronic diseases. Cardiovascular diseases, chronic obstructive pulmonary diseases, and malignant tumors have become the leading causes of death since the 1990s. Constant payments for maintaining the health status of a family member who has chronic diseases could exhaust household resources, undermining fiscal support for other necessities and eventually resulting in poverty. The purpose of this study is to probe to what degree health expenditure for chronic diseases can impoverish rural families and whether the New Cooperative Medical Scheme can effectively protect families with chronic patients against catastrophic health expenditures. We used data from the 4th National Health Services Survey conducted in July 2008 in China. The rural sample we included in the analysis comprised 39,054 households. We used both households suffering from medical impoverishment and households with catastrophic health expenditures to compare the financial protection for families having a chronic patient with different insurance coverage statuses. We used a logistic regression model to estimate the impact of different benefit packages on health financial protection for families having a chronic patient. An additional 10.53% of the families with a chronic patient were impoverished because of healthcare expenditure, which is more than twice the proportion in families without a chronic patient. There is a higher catastrophic health expenditure incidence in the families with a chronic patient. The results of logistic regression show that simply adding extra benefits did not reduce the financial risks. There is a lack of effective financial protection for healthcare expenditures for families with a chronic patient in rural China, even though there is a high coverage rate with the New Cooperative Medical Schemes. Given the coming universal coverage by the New Cooperative Medical Scheme and the increasing central government funds in the risk pool, effective financial protection for families should be possible through systematic reform of both financing mechanisms and payment methods.

  11. Measuring financial protection for health in families with chronic conditions in Rural China

    PubMed Central

    2012-01-01

    Background As the world’s largest developing country, China has entered into the epidemiological phase characterized by high life expectancy and high morbidity and mortality from chronic diseases. Cardiovascular diseases, chronic obstructive pulmonary diseases, and malignant tumors have become the leading causes of death since the 1990s. Constant payments for maintaining the health status of a family member who has chronic diseases could exhaust household resources, undermining fiscal support for other necessities and eventually resulting in poverty. The purpose of this study is to probe to what degree health expenditure for chronic diseases can impoverish rural families and whether the New Cooperative Medical Scheme can effectively protect families with chronic patients against catastrophic health expenditures. Methods We used data from the 4th National Health Services Survey conducted in July 2008 in China. The rural sample we included in the analysis comprised 39,054 households. We used both households suffering from medical impoverishment and households with catastrophic health expenditures to compare the financial protection for families having a chronic patient with different insurance coverage statuses. We used a logistic regression model to estimate the impact of different benefit packages on health financial protection for families having a chronic patient. Results An additional 10.53% of the families with a chronic patient were impoverished because of healthcare expenditure, which is more than twice the proportion in families without a chronic patient. There is a higher catastrophic health expenditure incidence in the families with a chronic patient. The results of logistic regression show that simply adding extra benefits did not reduce the financial risks. Conclusions There is a lack of effective financial protection for healthcare expenditures for families with a chronic patient in rural China, even though there is a high coverage rate with the New Cooperative Medical Schemes. Given the coming universal coverage by the New Cooperative Medical Scheme and the increasing central government funds in the risk pool, effective financial protection for families should be possible through systematic reform of both financing mechanisms and payment methods. PMID:23158260

  12. A successful renal transplantation for renal failure after dasatinib-induced thrombotic thrombocytopenic purpura in a patient with imatinib-resistant chronic myelogenous leukaemia on nilotinib.

    PubMed

    Martino, Suella; Daguindau, Etienne; Ferrand, Christophe; Bamoulid, Jamal; Hayette, Sandrine; Nicolini, F-E; Capellier, G; Deconinck, Eric; Larosa, Fabrice

    2013-01-01

    Second-generation tyrosine kinase inhibitors (TKI2) often induce molecular remission, and prolonged survival with a better tolerance in imatinib-resistant chronic myelogenous leukaemia (CML) patients. We report the case of a CML in first chronic phase who was diagnosed in August 2003 in a young 24 year-old Caucasian woman. Our patient received first imatinib and then dasatinib and nilotinib. Imatinib was well tolerated and she developed TTP/HUS on dasatinib without documented evolution of CML and finally obtained MR5.0 with nilotinib and without any side effect. This case also illustrates the absence of cross-resistance and side-effects between the different TKIs and the feasibility of kidney transplantation associated with a nilotinib treatment of CML allowing a continuing MR5.0 and no further side effects.

  13. A role for whey-derived lactoferrin and immunoglobulins in the attenuation of obesity-related inflammation and disease.

    PubMed

    Brimelow, Rachel E; West, Nicholas P; Williams, Lauren T; Cripps, Allan W; Cox, Amanda J

    2017-05-24

    Obesity is a strong predictive factor in the development of chronic disease and has now superseded undernutrition as a major public health issue. Chronic inflammation is one mechanism thought to link excess body weight with disease. Increasingly, the gut and its extensive population of commensal microflora are recognized as playing an important role in the development of obesity-related chronic inflammation. Obesity and a high fat diet are associated with altered commensal microbial communities and increased intestinal permeability which contributes to systemic inflammation as a result of the translocation of lipopolysaccharide into the circulation and metabolic endotoxemia. Various milk proteins are showing promise in the prevention and treatment of obesity and chronic low-grade inflammation via reductions in visceral fat, neutralization of bacteria at the mucosa and reduced intestinal permeability. In this review, we focus on evidence supporting the potential antiobesogenic and anti-inflammatory effects of bovine whey-derived lactoferrin and immunoglobulins.

  14. Meeting report on the Bellagio Conference 'prevention of vascular diseases in the emerging world: An approach to global health equity'.

    PubMed

    Dirks, J H; Robinson, S W; Alderman, M; Couser, W G; Grundy, S M; Smith, S C; Remuzzi, G; Unwin, N

    2006-10-01

    Representatives from five international organizations (International Society of Nephrology, World Heart Federation, International Diabetes Federation, International Atherosclerosis Federation, and International Society of Hypertension) participated in a strategic planning workshop in December 2005 in Bellagio, Italy sponsored by the Rockefeller Foundation. There were equal representatives from developed and developing countries. Global perspectives on diabetes and cardiovascular and renal diseases were presented, with special emphasis on China, India, Latin America, and Africa. The rationale and effectiveness of preventive measures were discussed. It was apparent that measures for primary prevention and early intervention for all the chronic vascular diseases are similar. The five organizations agreed that an integrated global approach to chronic vascular diseases is needed. They resolved to collaborate and work towards an integrated approach to chronic vascular diseases with the establishment of a 5-year plan for the prevention and treatment of chronic vascular diseases, including public advocacy, advising international and national agencies, and improving education and the practice of established approaches.

  15. Effect of ancestry on interleukin-10 haplotypes in chronic periodontitis.

    PubMed

    Lopes, Camile de Barros; Barroso, Regina Fatima Feio; Burbano, Rommel Mario Rodrigues; Garcia, Patricia Aleixo; Pinto, Pablo Diego do Carmo; Santos, Ney Pereira Carneiro Dos; Santos, Sidney Emanuel Batista; Ribeiro-Dos-Santos, Andrea Kely Campos

    2017-06-01

    Chronic periodontitis is caused by an inflammatory reaction of the periodontal tissues and alveolar bone. This inflammation is caused by periodontopathic bacteria located in the subgingival biofilm, resulting in inflammatory reactions that may lead to loss of attachment. This tissue destruction is a consequence of host immune and inflammatory responses to specific periodontal pathogens and their metabolic products. Cytokines modulate the immune response, altering its efficiency in the competition against pathogens and increasing periodontal susceptibility. This study investigated genetic polymorphisms in Interleukin 10 (A-1082G, C-819T and C-592A) in 205 individuals from an admixed Brazilian population. A significantly increased risk of developing chronic periodontitis was observed in individuals with low IL-10 production and Amerindian ancestry. These results suggest that the polymorphisms A-1082G, C-819T, and C-592A, which are associated with ancestry, are involved in the susceptibility to the development of chronic periodontitis in an admixed northern Brazilian population.

  16. [Suplemented restricted diet in old patients with chronic renal disease].

    PubMed

    Teplan, Vladimír

    2016-01-01

    In last decades was confirmed remarkable increase in number of old patients with chronic kidney disease. Despide of developments in dialysis technology and kidney transplantation there is a growing number of old patients who are not suitable for these methods. Recently were published data showing long-term effect of protein restricted diet supplemented with keto amino acids in elderly. Based on our results obtained in re-analysis of 3 000 patients we can confirm also good compliance and low risk of malnutrition.Key words: chronic kidney disease - keto amino acids - old age - restricted diet.

  17. Group Health’s Initiative To Avert Opioid Misuse And Overdose Among Patients With Chronic Noncancer Pain

    PubMed Central

    Trescott, Claire E.; Beck, Randi M.; Seelig, Michelle D.; Von Korff, Michael R.

    2012-01-01

    Increased opioid prescribing for chronic pain that is not due to cancer has been accompanied by large increases in abuse and overdose of prescription opioids. This paper describes how Group Health, a Seattle-based nonprofit health care system, implemented a major initiative to make opioid prescribing safer. In the initiative’s first nine months, clinicians developed documented care plans for almost 6,000 patients receiving long-term opioid therapy for chronic pain. Evaluation of the initiative’s effects on care processes and trends in adverse events is under way. PMID:21821559

  18. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice.

    PubMed

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2015-07-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams' drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 µg dl(-1) ). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 µg dl(-1). Copyright © 2014 John Wiley & Sons, Ltd.

  19. Early chronic lead exposure reduces exploratory activity in young C57BL/6J mice

    PubMed Central

    Flores-Montoya, Mayra Gisel; Sobin, Christina

    2014-01-01

    Research has suggested that chronic low-level lead exposure diminishes neurocognitive function in children. Tests that are sensitive to behavioral effects at lowest levels of lead exposure are needed for the development of animal models. In this study we investigated the effects of chronic low-level lead exposure on exploratory activity (unbaited nose poke task), exploratory ambulation (open field task) and motor coordination (Rotarod task) in pre-adolescent mice. C57BL/6J pups were exposed to 0 ppm (controls), 30 ppm (low-dose) or 230 ppm (high-dose) lead acetate via dams’ drinking water administered from birth to postnatal day 28, to achieve a range of blood lead levels (BLLs) from not detectable to 14.84 μg dl−1). At postnatal day 28, mice completed behavioral testing and were killed (n = 61). BLLs were determined by inductively coupled plasma mass spectrometry. The effects of lead exposure on behavior were tested using generalized linear mixed model analyses with BLL, sex and the interaction as fixed effects, and litter as the random effect. BLL predicted decreased exploratory activity and no threshold of effect was apparent. As BLL increased, nose pokes decreased. The C57BL/6J mouse is a useful model for examining effects of early chronic low-level lead exposure on behavior. In the C57BL/6J mouse, the unbaited nose poke task is sensitive to the effects of early chronic low-level lead exposure. This is the first animal study to show behavioral effects in pre-adolescent lead-exposed mice with BLL below 5 μg dl−1. PMID:25219894

  20. Chronic Swimming Exercise Ameliorates Low-Soybean-Oil Diet-Induced Spatial Memory Impairment by Enhancing BDNF-Mediated Synaptic Potentiation in Developing Spontaneously Hypertensive Rats.

    PubMed

    Cheng, Mei; Cong, Jiyan; Wu, Yulong; Xie, Jiacun; Wang, Siyuan; Zhao, Yue; Zang, Xiaoying

    2018-05-01

    Exercise and low-fat diets are common lifestyle modifications used for the treatment of hypertension besides drug therapy. However, unrestrained low-fat diets may result in deficiencies of low-unsaturated fatty acids and carry contingent risks of delaying neurodevelopment. While aerobic exercise shows positive neuroprotective effects, it is still unclear whether exercise could alleviate the impairment of neurodevelopment that may be induced by certain low-fat diets. In this research, developing spontaneously hypertensive rats (SHR) were treated with chronic swimming exercise and/or a low-soybean-oil diet for 6 weeks. We found that performance in the Morris water maze was reduced and long-term potentiation in the hippocampus was suppressed by the diet, while a combination treatment of exercise and diet alleviated the impairment induced by the specific low-fat diet. Moreover, the combination treatment effectively increased the expression of brain-derived neurotrophic factor (BDNF) and N-methyl-D-aspartic acid receptor (NMDAR), which were both down-regulated by the low-soybean-oil diet in the hippocampus of developing SHR. These findings suggest that chronic swimming exercise can ameliorate the low-soybean-oil diet-induced learning and memory impairment in developing SHR through the up-regulation of BDNF and NMDAR expression.

  1. Integration of Care in Management of CKD in Resource-Limited Settings.

    PubMed

    Okpechi, Ikechi G; Bello, Aminu K; Ameh, Oluwatoyin I; Swanepoel, Charles R

    2017-05-01

    The prevalence of noncommunicable diseases, including chronic kidney disease (CKD), continues to increase worldwide, and mortality from noncommunicable diseases is projected to surpass communicable disease-related mortality in developing countries. Although the treatment of CKD is expensive, unaffordable, and unavailable in many developing countries, the current structure of the health care system in such countries is not set up to deliver comprehensive care for patients with chronic conditions, including CKD. The World Health Organization Innovative Care for Chronic Conditions framework could be leveraged to improve the care of CKD patients worldwide, especially in resource-limited countries where high cost, low infrastructure, limited workforce, and a dearth of effective health policies exist. Some developing countries already are using established health systems for communicable disease control to tackle noncommunicable diseases such as hypertension and diabetes, therefore existing systems could be leveraged to integrate CKD care. Decision makers in developing countries must realize that to improve outcomes for patients with CKD, important factors should be considered, including enhancing CKD prevention programs in their communities, managing the political environment through involvement of the political class, involving patients and their families in CKD care delivery, and effective use of health care personnel. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Chronic air pollution and social deprivation as modifiers of the association between high temperature and daily mortality

    PubMed Central

    2014-01-01

    Background Heat and air pollution are both associated with increases in mortality. However, the interactive effect of temperature and air pollution on mortality remains unsettled. Similarly, the relationship between air pollution, air temperature, and social deprivation has never been explored. Methods We used daily mortality data from 2004 to 2009, daily mean temperature variables and relative humidity, for Paris, France. Estimates of chronic exposure to air pollution and social deprivation at a small spatial scale were calculated and split into three strata. We developed a stratified Poisson regression models to assess daily temperature and mortality associations, and tested the heterogeneity of the regression coefficients of the different strata. Deaths due to ambient temperature were calculated from attributable fractions and mortality rates were estimated. Results We found that chronic air pollution exposure and social deprivation are effect modifiers of the association between daily temperature and mortality. We found a potential interactive effect between social deprivation and chronic exposure with regards to air pollution in the mortality-temperature relationship. Conclusion Our results may have implications in considering chronically polluted areas as vulnerable in heat action plans and in the long-term measures to reduce the burden of heat stress especially in the context of climate change. PMID:24941876

  3. Chronic air pollution and social deprivation as modifiers of the association between high temperature and daily mortality.

    PubMed

    Benmarhnia, Tarik; Oulhote, Youssef; Petit, Claire; Lapostolle, Annabelle; Chauvin, Pierre; Zmirou-Navier, Denis; Deguen, Séverine

    2014-06-18

    Heat and air pollution are both associated with increases in mortality. However, the interactive effect of temperature and air pollution on mortality remains unsettled. Similarly, the relationship between air pollution, air temperature, and social deprivation has never been explored. We used daily mortality data from 2004 to 2009, daily mean temperature variables and relative humidity, for Paris, France. Estimates of chronic exposure to air pollution and social deprivation at a small spatial scale were calculated and split into three strata. We developed a stratified Poisson regression models to assess daily temperature and mortality associations, and tested the heterogeneity of the regression coefficients of the different strata. Deaths due to ambient temperature were calculated from attributable fractions and mortality rates were estimated. We found that chronic air pollution exposure and social deprivation are effect modifiers of the association between daily temperature and mortality. We found a potential interactive effect between social deprivation and chronic exposure with regards to air pollution in the mortality-temperature relationship. Our results may have implications in considering chronically polluted areas as vulnerable in heat action plans and in the long-term measures to reduce the burden of heat stress especially in the context of climate change.

  4. Policy Guidelines for Effective Inclusion and Reintegration of People with Chronic Diseases in the Workplace: National and European Perspectives

    PubMed Central

    Vlachou, Anastasia; Stavroussi, Panayiota; Roka, Olga; Vasilou, Evdokia; Papadimitriou, Dimitra; Scaratti, Chiara; Kadyrbaeva, Asel; Brecelj, Valentina; Svestkova, Olga; Tobiasz-Adamczyk, Beata; Finnvold, Jon Erik; Gruber, Sonja

    2018-01-01

    The increasing prevalence of chronic diseases among the European working age population, as well as the implications for the individual and societal level, underline the need for policy guidelines targeting the effective inclusion of persons with chronic diseases in the workplace. The aim of the present paper was to explore the perspectives of European and National-level stakeholders on existing strategies for work re-integration of persons with chronic diseases, and to provide policy guidelines. A highly-structured interview protocol was distributed to 58 National level stakeholders (policy makers, professionals and employers) from seven European countries. Additionally, 20 European organizations concerned with health-related issues and employment completed an online survey. The findings reveal that employment-related challenges remain largely unaddressed. Both national and European stakeholders considered the existing legislative frameworks inadequate and appraised the co-ordination for the implementation of employment re-integration policies as ineffective. Policies targeting at work re-integration of persons with chronic diseases at European and national level should focus on consistent cooperation among all key stakeholders, awareness raising to staff and management, dissemination of effective strategies, developing research and evaluation standards and establishing monitoring systems on inclusive labour markets. PMID:29534484

  5. Overview of the causes of chronic diarrhea in children

    USDA-ARS?s Scientific Manuscript database

    The major causes and the prevalence of chronic diarrhea differ between developed and developing countries. In the developing world, chronic diarrhea is typically associated with serial enteric infections and malnutrition; it is manifested by a chronic enteropathy, with impaired mucosal healing, and ...

  6. Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma.

    PubMed

    Murata, Miki; Yoshida, Katsunori; Yamaguchi, Takashi; Matsuzaki, Koichi

    2014-11-07

    Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future.

  7. Trauma and posttraumatic stress disorder in transcultural patients with chronic pain.

    PubMed

    Berger, Maximus; Piralic-Spitzl, Sanela; Aigner, Martin

    2014-01-01

    Traumatic events are commonly experienced in the general population and can lead to both psychological and physical consequences. While some may process the experienced event without developing trauma related symptoms in the long term, others develop persistent symptomatology in the form of chronic pain depending on the type of trauma as well as various other risk factors. The aim of this study was to examine the relationship of the number of lifetime traumas and chronic pain in a sample of transcultural patients to further develop existing research highlighting an association between the number of traumas and chronic pain that may be independent of a categorical diagnosis of PTSD. Using a case-control design, this study compared 29 chronic pain patients (Gerbershagen II/III) born in former Yugoslavia (21 female; age: 52.5 years, SD 7.3) to 21 patients of a general psychiatric sample who were matched by age- (±5 years), migratory-background, and gender. The number of traumas and PTSD symptomatology were assessed using the Harvard Trauma Questionnaire (HTQ). Somatisation, social dysfunction and anxiety were assessed by the General Health Questionnaire 28 (GHQ-28). The Beck Depression Inventory (BDI) was used to determine the presence of depression. 96.9 % of the chronic pain patients reported at least one traumatic event compared to 76.2 % within the control group (p = 0.029). Likewise, the mean number of reported traumas was significantly higher among the chronic pain group at 12 vs. 7 respectively (p = 0.024). Regarding anxiety, depression and social dysfunction, no significant difference between the two groups was found. Chronic pain patients with migratory background report an unusually high number of traumatic events. Clinicians should carefully screen for trauma history in this group of patients. The present study supports prior research suggesting a cumulative effect of trauma on chronic pain.

  8. Pediatric fear-avoidance model of chronic pain: Foundation, application and future directions

    PubMed Central

    Asmundson, Gordon JG; Noel, Melanie; Petter, Mark; Parkerson, Holly A

    2012-01-01

    The fear-avoidance model of chronic musculoskeletal pain has become an increasingly popular conceptualization of the processes and mechanisms through which acute pain can become chronic. Despite rapidly growing interest and research regarding the influence of fear-avoidance constructs on pain-related disability in children and adolescents, there have been no amendments to the model to account for unique aspects of pediatric chronic pain. A comprehensive understanding of the role of fear-avoidance in pediatric chronic pain necessitates understanding of both child/adolescent and parent factors implicated in its development and maintenance. The primary purpose of the present article is to propose an empirically-based pediatric fear-avoidance model of chronic pain that accounts for both child/adolescent and parent factors as well as their potential interactive effects. To accomplish this goal, the present article will define important fear-avoidance constructs, provide a summary of the general fear-avoidance model and review the growing empirical literature regarding the role of fear-avoidance constructs in pediatric chronic pain. Assessment and treatment options for children with chronic pain will also be described in the context of the proposed pediatric fear-avoidance model of chronic pain. Finally, avenues for future investigation will be proposed. PMID:23248813

  9. Managing Chronic Pain in Special Populations with Emphasis on Pediatric, Geriatric, and Drug Abuser Populations

    PubMed Central

    Baumbauer, Kyle M.; Young, Erin E.; Starkweather, Angela R.; Guite, Jessica W.; Russell, Beth S.; Manworren, Renee C.

    2015-01-01

    Synopsis Chronic pain represents a significant health and societal concern. In the adult population chronic pain can lead to loss of productivity, earning potential, and decreased quality of life. Research has typically focused on otherwise healthy adults with chronic pain conditions; however there appear to be distinct groups with increased vulnerability for the emergence of chronic pain. These groups may be defined by developmental status and/or life circumstances that increase the risk of injury or for which treatment of pain is less effective. Within the pediatric, geriatric, and drug abuser populations, chronic pain also represents a significant health issue, which can lead to increased absenteeism during school age years, as well as decreased quality of life and increased risk of additional adverse health conditions later in life. Currently, little is known about the mechanisms that encourage the development of chronic pain in these groups, and, consequently, pediatric, geriatric, and substance abuse patients represent challenging cohorts to manage. We focus on known anatomic, physiologic, and genetic mechanisms underlying chronic pain in these populations, and highlight the need for a multimodal approach from multiple healthcare professionals for management of chronic pain in those with the most risk. PMID:26614727

  10. Pediatric fear-avoidance model of chronic pain: foundation, application and future directions.

    PubMed

    Asmundson, Gordon J G; Noel, Melanie; Petter, Mark; Parkerson, Holly A

    2012-01-01

    The fear-avoidance model of chronic musculoskeletal pain has become an increasingly popular conceptualization of the processes and mechanisms through which acute pain can become chronic. Despite rapidly growing interest and research regarding the influence of fear-avoidance constructs on pain-related disability in children and adolescents, there have been no amendments to the model to account for unique aspects of pediatric chronic pain. A comprehensive understanding of the role of fear-avoidance in pediatric chronic pain necessitates understanding of both child⁄adolescent and parent factors implicated in its development and maintenance. The primary purpose of the present article is to propose an empirically-based pediatric fear-avoidance model of chronic pain that accounts for both child⁄adolescent and parent factors as well as their potential interactive effects. To accomplish this goal, the present article will define important fear-avoidance constructs, provide a summary of the general fear-avoidance model and review the growing empirical literature regarding the role of fear-avoidance constructs in pediatric chronic pain. Assessment and treatment options for children with chronic pain will also be described in the context of the proposed pediatric fear-avoidance model of chronic pain. Finally, avenues for future investigation will be proposed.

  11. [Specifications of motivational interviewing within a cognitive-behavioral therapy of chronic pain].

    PubMed

    Aguerre, C; Bridou, M; Laroche, F; Csillik, A; Jensen, M

    2015-12-01

    Cognitive and behavioral approach of chronic pain presents encouraging results by improving physical, functional and psychological states of chronic pain patients. This specific treatment is partially based on the acquisition of new adaptive strategies to help the patients to manage more effectively chronic pain and to improve subsequently their subjective well-being. This requires in parallel to give up noxious emotional, cognitive and behavioral attitudes towards pain. Now, we have to admit that numerous therapeutic failures are directly imputable to difficulties introducing and making the indispensable changes continue in pursuit of the fixed therapeutic objectives. Readiness to change could play a considerable role in the success or not of chronic pain treatment. The main objective of this article is to present the data of the current literature concerning the specificities of the process of change in the field of the chronic pain. We present a review of the literature describing at first, the psychological progress made by chronic pain patients longing to manage their suffering better via the trans-theoretical model of intentional change. Secondly, we develop the contributions of the technique of motivational interviewing in the improvement of chronic pain treatment. The identification of the motivational profile of chronic pain patients will determine how motivational interviewing can be conducted to improve their readiness for change. There are several strategies used with chronic pain patients in pre-contemplative and contemplative stages. Therapists may facilitate the problem recognition (help chronic pain patients to become aware of and identify the nature of the difficulties they face when trying to cope with their physical suffering); increase the personal concern (empowering chronic pain patients so that they feel fully involved in what they offer and invest in the therapy); develop the intention of change (ensure that the change becomes truly intentional); cultivate optimism (to help chronic pain patients to consider the present situation as being less desperate than it seems); ask open-ended questions (the direct questioning can be used to specify a request or reveal ambivalence about change); present personal feedback (the therapist provides the patient with a maximum of information that may help to appreciate the true value of the effectiveness of their current management of pain); review consequences of change versus non-change (to review the plausible positive (pros) and negative (cons) consequences of change); and summarizing (to summarize the key points discussed during the interview). In the active stage, therapists may use other strategies like: developing a plan for change (to suggest the adoption of certain coping strategies with pain); providing information advice (provide information advice in order to help chronic pain patients to determine how they will take concrete steps to initiate change); and using a change plan worksheet (help chronic pain patients to develop a synthetic view of the change process they will undertake). The various strategies discussed in this article are intended to accompany chronic pain patients to a process of change to help them consider a fundamental change in their ways of managing pain, when they are insufficient, ineffective and/or unintentionally aggravating their situation. It is important to help chronic pain patients to become aware of the nature of the adaptive problems they face, but also opportunities for change that are offered in order to encourage them to manage more efficiently and more autonomously their physical and mental suffering. In this context of openness to change, motivational interviewing can be an invaluable help to build a good therapeutic alliance in order to maximize the impact of supported global and multidimensional chronic pain by including a cognitive-behavioral approach for example. Copyright © 2014 L’Encéphale, Paris, 2007. All rights reserved.

  12. Psychological interventions for mental health disorders in children with chronic physical illness: a systematic review.

    PubMed

    Bennett, Sophie; Shafran, Roz; Coughtrey, Anna; Walker, Susan; Heyman, Isobel

    2015-04-01

    Children with chronic physical illness are significantly more likely to develop common psychiatric symptoms than otherwise healthy children. These children therefore warrant effective integrated healthcare yet it is not established whether the known, effective, psychological treatments for symptoms of common childhood mental health disorders work in children with chronic physical illness. EMBASE, MEDLINE, PsycINFO and CINAHL databases were searched with predefined terms relating to evidence-based psychological interventions for psychiatric symptoms in children with chronic physical illness. We included all studies (randomised and non-randomised designs) investigating interventions aimed primarily at treating common psychiatric symptoms in children with a chronic physical illness in the review. Two reviewers independently assessed the relevance of abstracts identified, extracted data and undertook quality analysis. Ten studies (209 children, including 70 in control groups) met the criteria for inclusion in the review. All studies demonstrated some positive outcomes of cognitive behavioural therapy for the treatment of psychiatric symptoms in children with chronic physical illness. Only two randomised controlled trials, both investigating interventions for symptoms of depression, were found. There is preliminary evidence that cognitive behavioural therapy has positive effects in the treatment of symptoms of depression and anxiety in children with chronic physical illness. However, the current evidence base is weak and fully powered randomised controlled trials are needed to establish the efficacy of psychological treatments in this vulnerable population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats.

    PubMed

    Smith, Brittany L; Morano, Rachel L; Ulrich-Lai, Yvonne M; Myers, Brent; Solomon, Matia B; Herman, James P

    2017-11-22

    The late adolescent period is characterized by marked neurodevelopmental and endocrine fluctuations in the transition to early adulthood. Adolescents are highly responsive to the external environment, which enhances their ability to adapt and recover from challenges when given nurturing influences, but also makes them vulnerable to aberrant development when exposed to prolonged adverse situations. Female rats are particularly sensitive to the effects of chronic stress in adolescence, which manifests as passive coping strategies and blunted hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood. We sought to intervene by exposing adolescent rats to environmental enrichment (EE) immediately prior to and during chronic stress, hypothesizing that EE would minimize or prevent the long-term effects of stress that emerge in adult females. To test this, we exposed male and female rats to EE on postnatal days (PND) 33-60 and implemented chronic variable stress (CVS) on PND 40-60. CVS consisted of twice-daily unpredictable stressors. Experimental groups included: CVS/unenriched, unstressed/EE, CVS/EE and unstressed/unenriched (n = 10 of each sex/group). In adulthood, we measured behavior in the open field test and forced swim test (FST) and collected blood samples following the FST. We found that environmental enrichment given during the adolescent period prevented the chronic stress-induced transition to passive coping in the FST and reversed decreases in peak adrenocortical responsiveness observed in adult females. Adolescent enrichment had little to no effect on males or unstressed females tested in adulthood, indicating that beneficial effects are specific to females that were exposed to chronic stress.

  14. Association between organizational capacity and involvement in chronic disease prevention programming among Canadian public health organizations.

    PubMed

    Hanusaik, Nancy; Sabiston, Catherine M; Kishchuk, Natalie; Maximova, Katerina; O'Loughlin, Jennifer

    2015-04-01

    In the context of the emerging field of public health services and systems research, this study (i) tested a model of the relationships between public health organizational capacity (OC) for chronic disease prevention, its determinants (organizational supports for evaluation, partnership effectiveness) and one possible outcome of OC (involvement in core chronic disease prevention practices) and (ii) examined differences in the nature of these relationships among organizations operating in more and less facilitating external environments. OC was conceptualized as skills and resources/supports for chronic disease prevention programming. Data were from a census of 210 Canadian public health organizations with mandates for chronic disease prevention. The hypothesized relationships were tested using structural equation modeling. Overall, the results supported the model. Organizational supports for evaluation accounted for 33% of the variance in skills. Skills and resources/supports were directly and strongly related to involvement. Organizations operating within facilitating external contexts for chronic disease prevention had more effective partnerships, more resources/supports, stronger skills and greater involvement in core chronic disease prevention practices. Results also suggested that organizations functioning in less facilitating environments may not benefit as expected from partnerships. Empirical testing of this conceptual model helps develop a better understanding of public health OC. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway.

    PubMed

    Ibarra-Lecue, Inés; Mollinedo-Gajate, Irene; Meana, J Javier; Callado, Luis F; Diez-Alarcia, Rebeca; Urigüen, Leyre

    2018-04-27

    Long-term use of potent cannabis during adolescence increases the risk of developing schizophrenia later in life, but to date, the mechanisms involved remain unknown. Several findings suggest that the functional selectivity of serotonin 2A receptor (5-HT2AR) through inhibitory G-proteins is involved in the molecular mechanisms responsible for psychotic symptoms. Moreover, this receptor is dysregulated in the frontal cortex of schizophrenia patients. In this context, studies involving cannabis exposure and 5-HT2AR are scarce. Here, we tested in mice the effect of an early chronic Δ 9 -tetrahydrocannabinol (THC) exposure on cortical 5-HT2AR expression, as well as on its in vivo and in vitro functionality. Long-term exposure to THC induced a pro-hallucinogenic molecular conformation of the 5-HT2AR and exacerbated schizophrenia-like responses, such as prepulse inhibition disruption. Supersensitive coupling of 5-HT2AR toward inhibitory Gαi1-, Gαi3-, Gαo-, and Gαz-proteins after chronic THC exposure was observed, without changes in the canonical Gαq/11-protein pathway. In addition, we found that inhibition of Akt/mTOR pathway by rapamycin blocks the changes in 5-HT2AR signaling pattern and the supersensitivity to schizophrenia-like effects induced by chronic THC. The present study provides the first evidence of a mechanistic explanation for the relationship between chronic cannabis exposure in early life and increased risk of developing psychosis-like behaviors in adulthood.

  16. Increased glutamate synaptic transmission in the nucleus raphe magnus neurons from morphine-tolerant rats.

    PubMed

    Bie, Bihua; Pan, Zhizhong Z

    2005-02-09

    Currently, opioid-based drugs are the most effective pain relievers that are widely used in the treatment of pain. However, the analgesic efficacy of opioids is significantly limited by the development of tolerance after repeated opioid administration. Glutamate receptors have been reported to critically participate in the development and maintenance of opioid tolerance, but the underlying mechanisms remain unclear. Using whole-cell voltage-clamp recordings in brainstem slices, the present study investigated chronic morphine-induced adaptations in glutamatergic synaptic transmission in neurons of the nucleus raphe magnus (NRM), a key supraspinal relay for pain modulation and opioid analgesia. Chronic morphine significantly increased glutamate synaptic transmission exclusively in one class of NRM cells that contains mu-opioid receptors in a morphine-tolerant state. The adenylyl cyclase activator forskolin and the cAMP analog 8-bromo-cAMP mimicked the chronic morphine effect in control neurons and their potency in enhancing the glutamate synaptic current was significantly increased in neurons from morphine-tolerant rats. MDL12330a, an adenylyl cyclase inhibitor, and H89, a protein kinase A (PKA) inhibitor, reversed the increase in glutamate synaptic transmission induced by chronic morphine. In addition, PMA, a phorbol ester activator of protein kinase C (PKC), also showed an increased potency in enhancing the glutamate synaptic current in these morphine-tolerant cells. The PKC inhibitor GF109203X attenuated the chronic morphine effect. Taken together, these results suggest that chronic morphine increases presynaptic glutamate release in mu receptor-containing NRM neurons in a morphine-tolerant state, and that the increased glutamate synaptic transmission appears to involve an upregulation of both the cAMP/PKA pathway and the PKC pathway. This glutamate-mediated activation of these NRM neurons that are thought to facilitate spinal pain transmission may contribute to the reduced opioid analgesia during opioid tolerance.

  17. Nanoparticle-based Therapies for Wound Biofilm Infection: Opportunities and Challenges

    PubMed Central

    Kim, Min-Ho

    2016-01-01

    Clinical data from human chronic wounds implicates biofilm formation with the onset of wound chronicity. Despite the development of novel antimicrobial agents, the cost and complexity of treating chronic wound infections associated with biofilms remain a serious challenge, which necessitates the development of new and alternative approaches for effective anti-biofilm treatment. Recent advancement in nanotechnology for developing a new class of nanoparticles that exhibit unique chemical and physical properties holds promise for the treatment of biofilm infections. Over the last decade, nanoparticle-based approaches against wound biofilm infection have been directed toward developing nanoparticles with intrinsic antimicrobial properties, utilizing nanoparticles for controlled antimicrobials delivery, and applying nanoparticles for antibacterial hyperthermia therapy. In addition, a strategy to functionalize nanoparticles towards enhanced penetration through the biofilm matrix has been receiving considerable interest recently by means of achieving an efficient targeting to the bacterial cells within biofilm matrix. This review summarizes and highlights the recent development of these nanoparticle-based approaches as potential therapeutics for controlling wound biofilm infection, along with current challenges that need to be overcome for their successful clinical translation. PMID:26955044

  18. Progress and Prospects of Anti-HBV Gene Therapy Development

    PubMed Central

    Maepa, Mohube B.; Roelofse, Ilke; Ely, Abdullah; Arbuthnot, Patrick

    2015-01-01

    Despite the availability of an effective vaccine against hepatitis B virus (HBV), chronic infection with the virus remains a major global health concern. Current drugs against HBV infection are limited by emergence of resistance and rarely achieve complete viral clearance. This has prompted vigorous research on developing better drugs against chronic HBV infection. Advances in understanding the life cycle of HBV and improvements in gene-disabling technologies have been impressive. This has led to development of better HBV infection models and discovery of new drug candidates. Ideally, a regimen against chronic HBV infection should completely eliminate all viral replicative intermediates, especially covalently closed circular DNA (cccDNA). For the past few decades, nucleic acid-based therapy has emerged as an attractive alternative that may result in complete clearance of HBV in infected patients. Several genetic anti-HBV strategies have been developed. The most studied approaches include the use of antisense oligonucleotides, ribozymes, RNA interference effectors and gene editing tools. This review will summarize recent developments and progress made in the use of gene therapy against HBV. PMID:26263978

  19. Methodological recommendations for comparative research on the treatment of chronic wounds.

    PubMed

    Sonnad, S S; Goldsack, J C; Mohr, P; Tunis, S

    2013-09-01

    To provide specific recommendations to product developers and clinical researchers on the design of comparative effectiveness studies for the treatment of chronic wounds, specifically those pertaining to arterial and venous-disease related ulcers, diabetic foot ulcers, pressure ulcers and burn wounds. The recommendations were developed based on a process defined by the Center for Medical Technology Policy (CMTP). After selecting the subject area, semi-structured phone interviews were conducted by one of the authors (SSS) with representatives of payers, manufacturers, clinicians, clinician/researchers and patient advocates. Next, a broad range of stakeholders participated in a meeting convened by CMTP to determine their needs. A technical working group comprising key stakeholders then participated in clarifying recommendations developed by CMTP staff and adding important considerations for their implementation. The resulting draft document was finalised based on public and solicited comment from individual manufacturers; a consortium of product developers and manufacturers; and an alliance of physicians, providers, manufacturers and patient organisations. This article is a summary of the full effectiveness guidance document. To address the needs of patients, clinicians, guideline developers, payers and other post-regulatory decision makers, this work makes ten recommendations to guide comparative effectiveness research for chronic wound care. These recommendations fall into four categories: study design, population, comparators and outcomes. This paper suggests that using the recommendations outlined to conduct comparative effectiveness research on treatments for chronic wound therapies would facilitate trials that provide patients, clinicians, and payers with the information they need to make optimal treatment decisions. These recommendations focus on design changes that would have the largest impact in improving the usability of the results by decision makers and provide specific guidance on the design of prospective studies intended to inform decision making by patients, clinicians and payers. There were no external sources of funding for these recommendations. The Value Institute and the Center for Medical Technology Policy (CMTP) are both private, non-profit organisations. The authors have no financial, commercial or social conflicts of interest to declare with respect to the article or its content.

  20. Patient-controlled analgesia: therapeutic interventions using transdermal electro-activated and electro-modulated drug delivery.

    PubMed

    Indermun, Sunaina; Choonara, Yahya E; Kumar, Pradeep; Du Toit, Lisa C; Modi, Girish; Luttge, Regina; Pillay, Viness

    2014-02-01

    Chronic pain poses a major concern to modern medicine and is frequently undertreated, causing suffering and disability. Patient-controlled analgesia, although successful, does have limitations. Transdermal delivery is the pivot to which analgesic research in drug delivery has centralized, especially with the confines of needle phobias and associated pain related to traditional injections, and the existing limitations associated with oral drug delivery. Highlighted within is the possibility of further developing transdermal drug delivery for chronic pain treatment using iontophoresis-based microneedle array patches. A concerted effort was made to review critically all available therapies designed for the treatment of chronic pain. The drug delivery systems developed for this purpose and nondrug routes are elaborated on, in a systematic manner. Recent developments and future goals in transdermal delivery as a means to overcome the individual limitations of the aforementioned delivery routes are represented as well. The approval of patch-like devices that contain both the microelectronic-processing mechanism and the active medicament in a small portable device is still awaited by the pharmaceutical industry. This anticipated platform may provide transdermal electro-activated and electro-modulated drug delivery systems a feasible attempt in chronic pain treatment. Iontophoresis has been proven an effective mode used to administer ionized drugs in physiotherapeutic, diagnostic, and dermatological applications and may be an encouraging probability for the development of devices and aids in the treatment of chronic pain. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  1. Hypoxic alligator embryos: chronic hypoxia, catecholamine levels and autonomic responses of in ovo alligators.

    PubMed

    Eme, John; Altimiras, Jordi; Hicks, James W; Crossley, Dane A

    2011-11-01

    Hypoxia is a naturally occurring environmental challenge for embryonic reptiles, and this is the first study to investigate the impact of chronic hypoxia on the in ovo development of autonomic cardiovascular regulation and circulating catecholamine levels in a reptile. We measured heart rate (f(H)) and chorioallantoic arterial blood pressure (MAP) in normoxic ('N21') and hypoxic-incubated ('H10'; 10% O(2)) American alligator embryos (Alligator mississippiensis) at 70, 80 and 90% of development. Embryonic alligator responses to adrenergic blockade with propranolol and phentolamine were very similar to previously reported responses of embryonic chicken, and demonstrated that embryonic alligator has α and β-adrenergic tone over the final third of development. However, adrenergic tone originates entirely from circulating catecholamines and is not altered by chronic hypoxic incubation, as neither cholinergic blockade with atropine nor ganglionic blockade with hexamethonium altered baseline cardiovascular variables in N21 or H10 embryos. In addition, both atropine and hexamethonium injection did not alter the generally depressive effects of acute hypoxia - bradycardia and hypotension. However, H10 embryos showed significantly higher levels of noradrenaline and adrenaline at 70% of development, as well as higher noradrenaline at 80% of development, suggesting that circulating catecholamines reach maximal levels earlier in incubation for H10 embryos, compared to N21 embryos. Chronically elevated levels of catecholamines may alter the normal balance between α and β-adrenoreceptors in H10 alligator embryos, causing chronic bradycardia and hypotension of H10 embryos measured in normoxia. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Ziconotide for treatment of severe chronic pain.

    PubMed

    Schmidtko, Achim; Lötsch, Jörn; Freynhagen, Rainer; Geisslinger, Gerd

    2010-05-01

    Pharmacological management of severe chronic pain is difficult to achieve with currently available analgesic drugs, and remains a large unmet therapeutic need. The synthetic peptide ziconotide has been approved by the US Food and Drug Administration and the European Medicines Agency for intrathecal treatment of patients with severe chronic pain that is refractory to other treatment modalities. Ziconotide is the first member in the new drug class of selective N-type voltage-sensitive calcium-channel blockers. The ziconotide-induced blockade of N-type calcium channels in the spinal cord inhibits release of pain-relevant neurotransmitters from central terminals of primary afferent neurons. By this mechanism, ziconotide can effectively reduce pain. However, ziconotide has a narrow therapeutic window because of substantial CNS side-effects, and thus treatment with ziconotide is appropriate for only a small subset of patients with severe chronic pain. We provide an overview of the benefits and limitations of intrathecal ziconotide treatment and review potential future developments in this new drug class. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure

    PubMed Central

    Zhang, Zhi-Hao; Vaziri, Nosratola D.; Wei, Feng; Cheng, Xian-Long; Bai, Xu; Zhao, Ying-Yong

    2016-01-01

    Chronic renal failure (CRF) is a major public health problem worldwide. Earlier studies have revealed salutary effects of rhubarb extracts in CRF. In this study, we employed lipidomic and metabolomic approaches to identify the plasma biomarkers and to determine the effect of treatment with petroleum ether, ethyl acetate and n-butanol extracts of rhubarb in a rat model of CRF with adenine-induced chronic tubulointerstitial nephropathy. In addition, clinical biochemistry, histological evaluation and pro-fibrotic protein expression were analyzed. Significant changes were found between the CRF and control groups representing characteristic phenotypes of rats with CRF. Treatment with the three rhubarb extracts improved renal injury and dysfunction, either fully or partially reversed the plasma metabolites abnormalities and attenuated upregulation of pro-fibrotic proteins including TGF-β1, α-SMA, PAI-1, CTGF, FN and collagen-1. The nephroprotective effect of ethyl acetate extract was better than other extracts. The differential metabolites were closely associated with glycerophospholipid, fatty acid and amino acid metabolisms. The results revealed a strong link between renal tubulointerstitial fibrosis and glycerophospholipid metabolism and L-carnitine metabolism in the development of CRF. Amelioration of CRF with the three rhubarb extracts was associated with the delayed development and/or reversal the disorders in key metabolites associated with adenine-induced CRF. PMID:26903149

  4. Mazindol: anorectic and behavioral effects in female rats.

    PubMed

    Mattei, R; Carlini, E A

    1995-01-01

    The anorectic and behavioral effects of mazindol (2.5, 5 and 10 mg/kg) were determined. The experiments comprized acute and chronic administration to female rats, and the effects were compared with those produced by 2.5 mg/kg of methamphetamine. The following evaluation parameters were considered: food intake, body weight, motor activity, and stereotyped behavior. Acute administration of the three doses of mazindol, as well as of the methamphetamine dose, decreased food intake. Administered chronically to female rats, mazindol (5 and 10 mg/kg) and methamphetamine induced loss of body weight during the first fifteen days. However, weight was subsequently regained by the animals, indicating development of tolerance. Mazindol (10 mg/kg) and methamphetamine produced an increase in motor activity. This increase was, however, not observed after chronic treatment, suggesting development of tolerance. Additionally, mazindol induced noticeable dose-dependent effects, involving stereotyped behavior (sniffing, continuous licking, false bites), similar to those produced by methamphetamine. Verticalization, however, was only observed after administration of 2.5 and 5 mg/kg of mazindol, and was absent after administration of the higher dose of mazindol as well as of methamphetamine. Finally, it should be stressed that features of stereotyped behavior induced by both drugs, such as licking, false bites, sniffing and verticalization, were very similar.

  5. Multiculturally Sensitive Mental Health Scale (MSMHS): Development, Factor Analysis, Reliability, and Validity

    ERIC Educational Resources Information Center

    Chao, Ruth Chu-Lien; Green, Kathy E.

    2011-01-01

    Effectively and efficiently diagnosing African Americans' mental health has been a chronically unresolved challenge. To meet this challenge we developed a tool to better understand African Americans' mental health: the Multiculturally Sensitive Mental Health Scale (MSMHS). Three studies reporting the development and initial validation of the MSMHS…

  6. Memantine and dizocilpine interactions with antinociceptive or discriminative stimulus effects of morphine in rats after acute or chronic treatment with morphine

    PubMed Central

    Chen, Yukun; Evola, Marianne

    2013-01-01

    Rationale Memantine is a N-methyl-d-aspartic acid receptor (NMDAR) channel blocker that binds to dizocilpine sites and appears well tolerated during chronic use. Published studies suggest NMDAR antagonists prevent development of tolerance to effects of morphine by blocking NMDAR hyperactivation. Objectives We sought to compare effects of memantine to those of the more frequently studied dizocilpine and to evaluate memantine as a potential adjunct to modify tolerance to mu-opioid receptor agonists. Methods Sprague–Dawley rats were trained to discriminate morphine (3.2 mg/kg) and saline under fixed ratio 15 schedules of food delivery. Potency and maximal stimulus or rate-altering effects of cumulative doses of morphine were examined 30 min after pretreatment with dizocilpine (0.032–0.1 mg/kg) or memantine (5–10 mg/kg) and after chronic treatment with combinations of dizocilpine or memantine and morphine, 10 mg/kg twice daily, for 6 to 14 days. Effects of dizocilpine or memantine on morphine antinociception were examined in a 55 °C water tail-withdrawal assay with drug treatments parallel to those in discrimination studies. Results Acutely, memantine attenuated while dizocilpine potentiated the stimulus and antinociceptive effects of morphine. Neither chronic dizocilpine nor memantine blocked tolerance to the stimulus effects of morphine. In contrast, combined-treatment with dizocilpine (0.1 mg/kg) blocked tolerance to antinociceptive effects of lower (0.1∼3.2 mg/kg) but not higher doses of morphine, whereas memantine did not block tolerance. Conclusions Memantine and dizocilpine interacted differently with morphine, possibly due to different NMDAR binding profiles. The lack of memantine-induced changes in morphine tolerance suggests memantine may not be a useful adjunct in chronic pain management. PMID:22864944

  7. Gonadal hormones do not alter the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol in adult rats

    PubMed Central

    Wakley, Alexa A; Wiley, Jenny L; Craft, Rebecca M

    2015-01-01

    The purpose of this study was to determine whether sex differences in the development of antinociceptive tolerance to delta-9-tetrahydrocannabinol (THC) are due to activational effects of gonadal hormones. Rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX). GDX females received no hormone replacement (GDX+0), estradiol (GDX+E2), progesterone (GDX+P4), or both (GDX+E2/P4). GDX male rats received no hormone (GDX+0) or testosterone (GDX+T). Two weeks later, antinociceptive potency of THC was determined (pre-chronic test) on the warm water tail withdrawal and paw pressure assays. Vehicle or a sex-specific THC dose (females, 5.7 mg/kg, males, 9.9 mg/kg) was administered twice-daily for 9 days, then the THC dose-effect curves were re-determined (post-chronic test). On the pre-chronic test (both assays), THC was more potent in sham-GDX females than males, and gonadectomy did not alter this sex difference. In GDX females, P4 significantly decreased THC’s antinociceptive potency, whereas E2 had no effect. In GDX males, T did not alter THC’s antinociceptive potency. After chronic THC treatment, THC’s antinociceptive potency was decreased more in sham-GDX females than males, on the tail withdrawal test; this sex difference in tolerance was not altered in GDX or hormone-treated groups. These results suggest that greater antinociceptive tolerance in females, which occurred despite females receiving 40% less THC than males, is not due to activational effects of gonadal hormones. PMID:25863271

  8. Laparoscopic Roux En Y Esophago-Jejunostomy for Chronic Leak/Fistula After Laparoscopic Sleeve Gastrectomy.

    PubMed

    Mahmoud, Maysoon; Maasher, Ahmed; Al Hadad, Mohamed; Salim, Elnazeer; Nimeri, Abdelrahman A

    2016-03-01

    Leak following laparoscopic sleeve gastrectomy (LSG) is one of the most serious and devastating complications. Endoscopic stents can treat most early LSG leaks, but is not as effective for chronic LSG leaks/fistulae. The surgical options to treat a chronic leak/fistula after LSG are laparoscopic Roux en Y esophago-jejunostomy (LRYEJ) or laparoscopic Roux en Y fistulo-jejunostomy. We reviewed our prospective database for all patients with leak after LSG treated with LRYEJ. We have described our algorithm for managing LSG previously. We prefer to optimize the nutritional status of patients with enteral rather than parenteral nutrition and drain all collections prior to LRYEJ. We have treated four patients utilizing our technique of LRYEJ. Initial endoscopic stent placement was attempted in all four patients (two failed to resolve (50 %) and two had distal stenosis at the incisura not amenable to endoscopic stenting). We utilized enteral feeding through either naso-jejunal (NJ) or jejunostomy tube feeding in 3/4 (75 %) of patients, and in one patient with stenosis, we could not introduce a NJ tube endoscopically due to tight stricture. This patient was placed on total parenteral nutrition (TPN) and went on to develop pulmonary embolism. None of the patient developed leak after LRYEJ. The only patient with stenosis (25 %) had antecolic LRYEJ. In contrast, all patients who had retrocolic LRYGB laparoscopically did not develop stenosis. Laparoscopic Roux en Y esophago-jejunostomy for chronic leak/fistula after is safe and effective. Preoperative enteral nutrition is important.

  9. Effects of small increases in corticosterone levels on morphology, immune function, and feather development.

    PubMed

    Butler, Michael W; Leppert, Lynda L; Dufty, Alfred M

    2010-01-01

    Stressors encountered during avian development may affect an individual's phenotype, including immunocompetence, growth, and feather quality. We examined effects of simulated chronic low-level stress on American kestrel (Falco sparverius) nestlings. Continuous release of corticosterone, a hormone involved in the stress response, can model chronic stress in birds. We implanted 13-d-old males with either corticosterone-filled implants or shams and measured their growth, immune function, and feather coloration. We found no significant differences between groups at the end of the weeklong exposure period in morphometrics (mass, tarsus, wing length, and asymmetry), immunocompetence (cutaneous immunity, heterophil/lymphocyte ratio, and humoral immunity), or feather coloration. One week subsequent to implant removal, however, differences were detected. Sham-implanted birds had significantly longer wings and a reduced level of cutaneous immune function compared with those of birds given corticosterone-filled implants. Therefore, increases of only 2 ng/mL in basal corticosterone titer can have small but measurable effects on subsequent avian development.

  10. Chronic variable stress in fathers alters paternal and social behavior but not pup development in the biparental California mouse (Peromyscus californicus).

    PubMed

    Harris, Breanna N; de Jong, Trynke R; Yang, Vanessa; Saltzman, Wendy

    2013-11-01

    Stress and chronically elevated glucocorticoid levels have been shown to disrupt parental behavior in mothers; however, almost no studies have investigated corresponding effects in fathers. The present experiment tested the hypothesis that chronic variable stress inhibits paternal behavior and consequently alters pup development in the monogamous, biparental California mouse (Peromyscus californicus). First-time fathers were assigned to one of three experimental groups: chronic variable stress (CVS, n=8), separation control (SC, n=7), or unmanipulated control (UC, n=8). The CVS paradigm (3 stressors per day for 7 days) successfully stressed mice, as evidenced by increased baseline plasma corticosterone concentrations, increased adrenal mass, decreased thymus mass, and a decrease in body mass over time. CVS altered paternal and social behavior of fathers, but major differences were observed only on day 6 of the 7-day paradigm. At that time point, CVS fathers spent less time with their pairmate and pups, and more time autogrooming, as compared to UC fathers; SC fathers spent more time behaving paternally and grooming the female mate than CVS and UC fathers. Thus, CVS blocked the separation-induced increase in social behaviors observed in the SC fathers. Nonetheless, chronic stress in fathers did not appear to alter survival or development of their offspring: pups from the three experimental conditions did not differ in body mass gain over time, in the day of eye opening, or in basal or post-stress corticosterone levels. These results demonstrate that chronic stress can transiently disrupt paternal and social behavior in P. californicus fathers, but does not alter pup development or survival under controlled, non-challenging laboratory conditions. © 2013.

  11. Effects of Coffee Intake on Incident Chronic Kidney Disease: Community-Based Prospective Cohort Study.

    PubMed

    Jhee, Jong Hyun; Nam, Ki Heon; An, Seong Yeong; Cha, Min-Uk; Lee, Misol; Park, Seohyun; Kim, Hyoungnae; Yun, Hae-Ryong; Kee, Youn Kyung; Park, Jung Tak; Chang, Tae-Ik; Kang, Ea Wha; Yoo, Tae-Hyun; Kang, Shin-Wook; Han, Seung Hyeok

    2018-06-12

    Drinking coffee can raise public health problems, but the association between coffee and kidney disease is unknown. We studied whether coffee intake can affect the development of chronic kidney disease in the general population. We analyzed 8717 subjects with normal renal function recruited from the KoGES cohort. Based on food frequency questionnaire, coffee consumption was categorized into five groups: 0/week, <1 cup/week, 1-6 cups/week, 1 cup/day, and ≥2 cups/day. The primary outcome was incident chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 . The mean age of study subjects was 52.0 (8.8) years and 47.8% were male. Among the subjects, 52.8% were daily coffee consumers. During a mean follow-up of 11.3 [5.9-11.5] years, 9.5% of participants developed chronic kidney disease. The incident chronic kidney disease occurred less in daily coffee consumers. Unadjusted HRs was significantly lower in daily coffee consumers. In multivariable Cox model even after adjustment of blood pressure, hypertension, cardiovascular disease, diabetes, and amount of daily intake for caffeine-containing foods such as tea and chocolate, coffee consumers with 1 cup/day (HR, 0.76; 95% CI, 0.63-0.92) and ≥2 cups/day (HR, 0.80; 95% CI, 0.65-0.98) were associated with a lower risk of chronic kidney disease development than non-drinkers. Time-averaged and time-varying Cox models yielded similar results. The rates of decline in eGFR were lower in daily coffee consumers. Our findings suggest that daily coffee intake is associated with decreased risk of the development of CKD. Copyright © 2018. Published by Elsevier Inc.

  12. Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat.

    PubMed

    Hanak, Anne-Sophie; Malissin, Isabelle; Poupon, Joël; Risède, Patricia; Chevillard, Lucie; Mégarbane, Bruno

    2017-03-01

    Lithium overdose may result in encephalopathy and electroencephalographic abnormalities. Three poisoning patterns have been identified based on the ingested dose, previous treatment duration and renal function. Whether the severity of lithium-induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium-induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns. Lithium-induced encephalopathy was assessed and scored using continuous electroencephalography. We demonstrated that lithium overdose was consistently responsible for encephalopathy, the severity of which depended on the poisoning pattern. Acutely poisoned rats developed rapid-onset encephalopathy which reached a maximal grade of 2/5 at 6 h and disappeared at 24 h post-injection. Acute-on-chronically poisoned rats developed persistent and slightly fluctuating encephalopathy which reached a maximal grade of 3/5. Chronically poisoned rats developed rapid-onset but gradually increasing life-threatening encephalopathy which reached a maximal grade of 4/5. None of the acutely, 20% of the acute-on-chronically and 57% of the chronically lithium-poisoned rats developed seizures. The relationships between encephalopathy severity and lithium concentrations fitted a sigmoidal E max model based on cerebrospinal fluid concentrations in acute poisoning and brain concentrations in acute-on-chronic poisoning. In chronic poisoning, worsening of encephalopathy paralleled the increase in plasma lithium concentrations. The severity of lithium-induced encephalopathy is dependent on the poisoning pattern, which was previously shown to determine lithium accumulation in the brain. Our data support the proposition that electroencephalography is a sensitive tool for scoring lithium-related neurotoxicity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Chronic variable stress in fathers alters paternal and social behavior but not pup development in the biparental California mouse (Peromyscus californicus)

    PubMed Central

    Harris, Breanna N.; de Jong, Trynke R.; Yang, Vanessa; Saltzman, Wendy

    2013-01-01

    Stress and chronically elevated glucocorticoid levels have been shown to disrupt parental behavior in mothers; however, almost no studies have investigated corresponding effects in fathers. The present experiment tested the hypothesis that chronic variable stress inhibits paternal behavior and consequently alters pup development in the monogamous, biparental California mouse (Peromyscus californicus). First-time fathers were assigned to one of three experimental groups: chronic variable stress (CVS, n=8), separation control (SC, n=7), or unmanipulated control (UC, n=8). The CVS paradigm (3 stressors per day for 7 days) successfully stressed mice, as evidenced by increased baseline plasma corticosterone concentrations, increased adrenal mass, decreased thymus mass, and a decrease in body mass over time. CVS altered paternal and social behavior of fathers, but major differences were observed only on day 6 of the 7-day paradigm. At that time point, CVS fathers spent less time with their pairmate and pups, and more time autogrooming, as compared to UC fathers; SC fathers spent more time behaving paternally and grooming the female mate than CVS and UC fathers. Thus, CVS blocked the separation-induced increase in social behaviors observed in the SC fathers. Nonetheless, chronic stress in fathers did not appear to alter survival or development of their offspring: pups from the three experimental conditions did not differ in body mass gain over time, in day of eye opening, or in basal or post-stress corticosterone levels. These results demonstrate that chronic stress can transiently disrupt paternal and social behavior in P. californicus fathers, but does not alter pup development or survival under controlled, nonchallenging laboratory conditions. PMID:24157379

  14. Chronic pain during pregnancy: a review of the literature.

    PubMed

    Ray-Griffith, Shona L; Wendel, Michael P; Stowe, Zachary N; Magann, Everett F

    2018-01-01

    The majority of the reviews and studies on chronic pain in pregnancy have primarily focused on the pharmacological and non-pharmacological treatment options. The purpose of our review was to identify evidence-based clinical research for the evaluation and management of preexisting chronic pain in pregnancy, chronic pain associated with pregnancy, and chronic pain in relation to mode of delivery. A literature search was undertaken using the search engines PubMed, CINAHL, EBSCOhost, and Web of Science. Search terms used included "chronic pain" AND "pregnant OR pregnancy" OR "pregnancy complications" from inception through August 2016. The basis of this review was the 144 articles that met inclusion criteria for this review. Based on our review of the current literature, we recommend 7 guidelines for chronic pain management during and after pregnancy: 1) complete history and physical examination; 2) monitor patients for alcohol, nicotine, and substance use; 3) collaborate with patient to set treatment goals; 4) develop a management plan; 5) for opioids, use lowest effective dose; 6) formulate a pain management plan for labor and delivery; and 7) discuss reproductive health with women with chronic pain. The management of chronic pain associated with pregnancy is understudied. Obstetrical providers primarily manage chronic pain during pregnancy. Some general guidelines are provided for those health care providers until more information is available.

  15. Feasibility and effects of newly developed balance control trainer for mobility and balance in chronic stroke patients: a randomized controlled trial.

    PubMed

    Lee, So Hyun; Byun, Seung Deuk; Kim, Chul Hyun; Go, Jin Young; Nam, Hyeon Uk; Huh, Jin Seok; Jung, Tae Du

    2012-08-01

    To investigate the feasibility and effects of balance training with a newly developed Balance Control Trainer (BCT) that applied the concept of vertical movement for the improvements of mobility and balance in chronic stroke patients. Forty chronic stroke patients were randomly assigned to an experimental or a control group. The experimental group (n=20) underwent training with a BCT for 20 minutes a day, 5 days a week for 4 weeks, in addition to concurrent conventional physical therapy. The control group (n=20) underwent only conventional therapy for 4 weeks. All participants were assessed by: the Functional Ambulation Categories (FAC), 10-meter Walking Test (10mWT), Timed Up and Go test (TUG), Berg Balance Scale (BBS), Korean Modified Barthel Index (MBI), and Manual Muscle Test (MMT) before training, and at 2 and 4 weeks of training. There were statistically significant improvements in all parameters except knee extensor power at 2 weeks of treatment, and in all parameters except MBI which showed further statistically significant progress in the experimental group over the next two weeks (p<0.05). Statistically significant improvements on all measurements were observed in the experimental group after 4 weeks total. Comparing the two groups at 2 and 4 weeks of training respectively, 10mWT, TUG, and BBS showed statistically more significant improvements in the experimental group (p<0.05). Balance training with a newly developed BCT is feasible and may be an effective tool to improve balance and gait in ambulatory chronic stroke patients. Furthermore, it may provide additional benefits when used in conjunction with conventional therapies.

  16. Increasing the involvement of specialist physicians in chronic disease management.

    PubMed

    Taylor, Dylan; Lahey, Michele

    2008-01-01

    The Capital Health (CH) region in Alberta serves the population of the Edmonton area as well as a large referral population in western Canada. CH is responsible for the delivery of the spectrum of patient care, from inpatient to outpatient services. Growth in outpatient care, in particular, has led to the development of several ambulatory care facilities from which the delivery of care to several populations with a chronic disease will be coordinated. The traditional model of care delivery is unsuited to the management of chronic diseases. Physicians must be part of the planning and implementation of new models if they are to be successful and sustainable. The concept of integration into a delivery team is not well understood or practised. This is not conducive to the integration of specialist physicians into multidisciplinary teams in ambulatory care that serves the needs of patients from a large geographic area. Chronic disease management using the Chronic Care Model has proven to be an effective method of delivering care to this wide population. Specialist physicians have not always taken advantage of opportunities to be involved in the planning and development of such new health care projects. In CH, physician integration in the planning, development and implementation of this new model has proven vital to its success. We based our strategy for change on Wagner's Chronic Care Model. This involved eight steps, the first four of which have been completed and the fifth and sixth are underway. Five factors contributed to the successful integration of specialist physicians in chronic disease management: collaboration between disciplines and organizations; creating patient-centred services; organizational commitments; strong clinical leadership; and early involvement of clinicians.

  17. Quality improvement tools for chronic disease care--more effective processes are less likely to be implemented in developing countries.

    PubMed

    Hashim, Muhammad Jawad; Prinsloo, Adrianna; Mirza, Deen M

    2013-01-01

    Chronic disease services may be improved if care management processes (CMPs), such as disease-specific flowsheets and chronic disease registries, are used. The newly industrialized Gulf state health service has underdeveloped primary care but higher diabetes prevalence. This paper's aim is to investigate care management processes in United Arab Emirates (UAE) primary care clinics to explore these issues. A cross-sectional survey using self-administered questionnaires given to family physicians and nurses attending a UAE University workshop was used to collect data. All 38 participants completed the questionnaire: 68 per cent were women and 81 per cent physicians. Care management processes in use included: medical records, 76 per cent; clinical guidelines, 74 per cent; chronic disease care rooms, 74 per cent; disease-specific flowsheets, 61 per cent; medical record audits, 57 per cent; chronic disease nurse-educators, 58 per cent; electronic medical records (EMR), 34 per cent; and incentive plans based on clinical performance, 21 per cent. Only 62 per cent and 48 per cent reported that flowsheets and problem lists, respectively, were completed by physicians. Responses to the open-ended question included using traditional quality improvement (QI) approaches such as continuing education and staff meetings, but not proactive systems such as disease registries and self-management. The study used a small, non-random sample and the survey instrument's psychometric properties were not collected. Chronic disease care CMPs are present in UAE clinics but use is limited. Quality improvement should include disease registries, reminder-tracking systems, patient self-management support and quality incentives. This report highlights the lag regarding adopting more effective CMPs in developing countries.

  18. Development of a diabetes care management curriculum in a family practice residency program.

    PubMed

    Nuovo, Jim; Balsbaugh, Thomas; Barton, Sue; Davidson, Ellen; Fox-Garcia, Jane; Gandolfo, Angela; Levich, Bridget; Seibles, Joann

    2004-01-01

    Improving the quality of care for patients with chronic illness has become a high priority. Implementing training programs in disease management (DM) so the next generation of physicians can manage chronic illness more effectively is challenging. Residency training programs have no specific mandate to implement DM training. Additional barriers at the training facility include: 1) lack of a population-based perspective for service delivery; 2) weak support for self-management of illness; 3) incomplete implementation due to physician resistance or inertia; and 4) few incentives to change practices and behaviors. In order to overcome these barriers, training programs must take the initiative to implement DM training that addresses each of these issues. We report the implementation of a chronic illness management curriculum based on the Improving Chronic Illness Care (ICIC) Model. Features of this process included both patient care and learner objectives. These were: development of a multidisciplinary diabetes DM team; development of a patient registry; development of diabetes teaching clinics in the family practice center (nutrition, general management classes, and one-on-one teaching); development of a group visit model; and training the residents in the elements of the ICIC Model, ie, the community, the health system, self-management support, delivery system design, decision support, and clinical information systems. Barriers to implementing these curricular changes were: the development of a patient registry; buy-in from faculty, residents, clinic leadership, staff, and patients for the chronic care model; the ability to bill for services and maintain clinical productivity; and support from the health system key stakeholders for sustainability. Unique features of each training site will dictate differences in emphasis and structure; however, the core principles of the ICIC Model in enhancing self-management may be generalized to all sites.

  19. Stochastic modelling to assess economic effects of treatment of chronic subclinical mastitis caused by Streptococcus uberis.

    PubMed

    Steeneveld, Wilma; Swinkels, Jantijn; Hogeveen, Henk

    2007-11-01

    Chronic subclinical mastitis is usually not treated during the lactation. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of chronic subclinical mastitis caused by Streptococcus uberis. Factors in the model included the probability of cure after treatment, probability of the cow becoming clinically diseased, transmission of infection to other cows, and physiological effects of the infection. Using basic input parameters for Dutch circumstances, the average economic costs per cow of an untreated chronic subclinical mastitis case caused by Str. uberis in a single quarter from day of diagnosis onwards was euro109. With treatment, the average costs were higher (euro120). Thus, for the average cow, treatment was not efficient economically. However, the risk of high costs was much higher when cows with chronic subclinical mastitis were not treated. A sensitivity analysis showed that profitability of treatment of chronic subclinical Str. uberis mastitis depended on farm-specific factors (such as economic value of discarded milk) and cow-specific factors (such as day of diagnosis, duration of infection, amount of transmission to other cows and cure rate). Therefore, herd level protocols are not sufficient and decision support should be cow specific. Given the importance of cow-specific factors, information from the current model could be applied to automatic decision support systems.

  20. Chronic disease prevention and management: implications for health human resources in 2020.

    PubMed

    Orchard, Margo; Green, Esther; Sullivan, Terrence; Greenberg, Anna; Mai, Verna

    2008-01-01

    Through improved screening, detection, better and more targeted therapies and the uptake of evidence-based treatment guidelines, cancers are becoming chronic diseases. However, this good-news story has implications for human resource planning and resource allocation. Population-based chronic disease management is a necessary approach to deal with the growing burden of chronic disease in Canada. In this model, an interdisciplinary team works with and educates the patient to monitor symptoms, modify behaviours and self-manage the disease between acute episodes. In addition, the community as a whole is more attuned to disease prevention and risk factor management. Trusted, high-quality evidence-based protocols and healthy public policies that have an impact on the entire population are needed to minimize the harmful effects of chronic disease. Assuming we can overcome the challenges in recruitment, training and new role development, enlightened healthcare teams and community members will work together to maintain the population's health and wellness and to reduce the incidence and burden of chronic disease in Ontario.

  1. Effects of chronic perfluorooctanoic acid (PFOA) at low concentration on morphometrics, gene expression, and fecundity in zebrafish (Danio rerio).

    PubMed

    Jantzen, Carrie E; Toor, Fatima; Annunziato, Kate A; Cooper, Keith R

    2017-04-01

    Perfluorooctanoic acid (PFOA) is a persistent, toxic, anthropogenic chemical recalcitrant to biodegradation. Based on previous studies in lower and higher vertebrates, it was hypothesized that chronic, sub-lethal, embryonic exposure to PFOA in zebrafish (Danio rerio) would adversely impact fish development, survival, and fecundity. Zebrafish embryo/sac-fry were water exposed to 2.0 or 0nM PFOA from 3 to 120hpf, and juvenile to adult cohorts were fed spiked food (8 pM) until 6 months. After chronic exposure, PFOA exposed fish were significantly smaller in total weight and length. Gene expression analysis found a significant decrease of transporters slco2b1, slco4a1, slco3a1 and tgfb1a, and a significant increase of slco1d1 expression. PFOA exposed fish produced significantly fewer eggs with reduced viability and developmental stage delay in F 1 . Chronic, low-dose exposure of zebrafish to PFOA significantly altered normal development, survival and fecundity and would likely impact wild fish population fitness in watersheds chronically exposed to PFOA. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. [Social and organizational innovation to tackle the challenge of integrated care of the chronically ill].

    PubMed

    Nuño-Solinís, Roberto

    2014-01-01

    The increase in life expectancy, coupled with other factors, has led to an increase in the prevalence of chronic diseases and multiple morbidity. This has led to the need to develop new health and social care models, which will allow managing these efficiently and in a sustainable manner. In particular, there seems to be consensus on the need to move towards integrated, patient-centered, and more proactive care. Thus, in recent years, chronic care models have been developed at international, national and regional level, as well as introducing strategies to tackle the challenge of chronic illness. However, the implementation of actions facilitating the change towards this new model of care does not seem to be an easy task. This paper presents some of the strategic lines and initiatives carried out by the Department of Health of the Basque Government. These actions can be described within a social and organizational innovation framework, as a means for effective implementation of interventions and strategies that shape the model required for the improved care of chronic illnesses within a universal and tax-funded health system. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  3. 78 FR 63218 - Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ...] Draft Guidance for Industry on Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral... entitled ``Chronic Hepatitis C Virus Infection: Developing Direct-Acting Antiviral Drugs for Treatment... antiviral (DAA) drugs for the treatment of chronic hepatitis C. This guidance revises and replaces a...

  4. [Siblings of chronically ill adolescents: does chronic illness have effects on their development potentials?].

    PubMed

    Boeger, A; Seiffge-Krenke, I

    1996-12-01

    Sibling relationships have been studied by developmental psychologists for a long time. Whereas previous research on this topic was focused on examining variables such as gender, age differences and sibling sequence, recent research efforts have directed more attention towards understanding the functions siblings perform for one another and what kinds of emotional relationships exist between them. In this regard, we became interested in identifying the special burdens which siblings of chronically sick children and adolescents must deal with. Two case studies are presented here selected from the research findings obtained from investigation in our research project. Coping with chronic illness as seen in juvenile diabetes. These case studies demonstrate that healthy siblings of chronically sick adolescents may be subjected to considerable burdens and illustrate, as well, the kinds of coping mechanisms siblings adopt in order to deal with them.

  5. Relationship between chronic otitis media with effusion and overweight or obesity in children.

    PubMed

    Kaya, S; Selimoğlu, E; Cureoğlu, S; Selimoğlu, M A

    2017-10-01

    Otitis media with effusion and obesity are both common in childhood and might share some immunological alterations. This study aimed to investigate the relationship between chronic otitis media with effusion and childhood overweight or obesity, including the potential effects of adenoid or tonsillar hypertrophy on that relationship. This study included 60 children with chronic otitis media with effusion and 86 healthy children aged from 2 to 10 years. Measures of height and weight were used to calculate the body mass index, weight for height and weight z score. The prevalence of overweight or obesity was higher in children with chronic otitis media with effusion, according to the weight for height percentiles (p = 0.012). However, neither the presence of adenoid or tonsillar hypertrophy nor the degree of adenoid hypertrophy was associated with overweight or obesity. Overweight and obesity might be risk factors for developing chronic otitis media with effusion, or vice versa.

  6. Importance of Vaccine Safety in Children with Chronic Conditions--Experience at the Scientific Centre for Children's Health in Moscow, Russia.

    PubMed

    Grechukha, Tatiana A; Galitskaya, Marina G; Namazova-Baranova, Leyla S

    2015-01-01

    The risk of severe disease outcomes and complications of infectious diseases remains markedly increased in children and adolescents with chronic conditions. Specialized pediatric healthcare aims to improve quality of life in this high-risk group. One of the most important measures to achieve this goal is to improve immunization rates in this vulnerable population. This article aims to provide insight into models for the integration of infectious disease prevention into specialized healthcare for children with chronic conditions, by the example of the Department of Vaccines and Disease Prevention in Children with Chronic Conditions in Moscow, Russian Federation. The article highlights the importance of vaccine safety and effectiveness research in children with chronic conditions. Useful strategies for the optimization of vaccination rates in this population are presented, along with suggestions for the development of individual immunization schedules for different disease conditions.

  7. Chronic bystander infections and immunity to unrelated antigens

    PubMed Central

    Stelekati, Erietta; Wherry, E. John

    2012-01-01

    Chronic infections with persistent pathogens such as helminths, mycobacteria, Plasmodium and hepatitis viruses affect more than a third of the human population and are associated with increased susceptibility to other pathogens as well as reduced vaccine efficacy. Although these observations suggest an impact of chronic infections in modulating immunity to unrelated antigens, little is known regarding the underlying mechanisms. Here, we summarize evidence of the most prevalent infections affecting immunity to unrelated pathogens and vaccines, and discuss potential mechanisms of how different bystander chronic infections might impact immune responses. We suggest that bystander chronic infections affect different stages of host responses and may impact transmission of other pathogens, recognition and innate immune responses, priming and differentiation of adaptive effector responses, as well as the development and maintenance of immunological memory. Further understanding of the immunological effects of co-infection should provide opportunities to enhance vaccine efficacy and control infectious diseases. PMID:23084915

  8. Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study.

    PubMed

    Leufkens, T R M; Ramaekers, J G; de Weerd, A W; Riedel, W J; Vermeeren, A

    2014-07-01

    Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs. The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls). The study was conducted according to a 3 × 2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test. Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls. The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients.

  9. New Insights into the Effects of Chronic Kidney Failure and Dialysate Exposure on the Peritoneum.

    PubMed

    Vlahu, Carmen A; Aten, Jan; de Graaff, Marijke; van Veen, Henk; Everts, Vincent; de Waart, Dirk R; Struijk, Dirk G; Krediet, Raymond T

    ♦ INTRODUCTION: Chronic uremia and the exposure to dialysis solutions during peritoneal dialysis (PD) induce peritoneal alterations. Using a long-term peritoneal exposure model, we compared the effects of chronic kidney failure (CKD) itself and exposure to either a 'conventional' or a 'biocompatible' dialysis solution on peritoneal morphology and function. ♦ METHODS: Wistar rats (Harlan, Zeist, the Netherlands) were grouped into: normal kidney function (NKF), CKD induced by 70% nephrectomy, CKD receiving daily peritoneal infusions with 3.86% glucose Dianeal (CKDD), or Physioneal (both solutions from Baxter Healthcare, Castlebar, Ireland) (CKDP). At 16 weeks, a peritoneal function test was performed, and histology, ultrastructure, and hydroxyproline content of peritoneal tissue were assessed. ♦ RESULTS: Comparing CKD with NKF, peritoneal transport rates were higher, mesothelial cells (MC) displayed increased number of microvilli, blood and lymph vasculature expanded, vascular basal lamina appeared thicker, with limited areas of duplication, and fibrosis had developed. All alterations, except lymphangiogenesis, were enhanced by exposure to both dialysis fluids. Distinct MC alterations were observed in CKDD and CKDP, the latter displaying prominent basolateral protrusions. In addition, CKDP was associated with a trend towards less fibrosis compared to CKDD. ♦ CONCLUSIONS: Chronic kidney failure itself induced peritoneal alterations, which were in part augmented by exposure to glucose-based dialysis solutions. Overall, the conventional and biocompatible solutions had similar long-term effects on the peritoneum. Importantly, the latter may attenuate the development of fibrosis. Copyright © 2016 International Society for Peritoneal Dialysis.

  10. Interventions for the prediction and management of chronic postsurgical pain after total knee replacement: systematic review of randomised controlled trials.

    PubMed

    Beswick, Andrew D; Wylde, Vikki; Gooberman-Hill, Rachael

    2015-05-12

    Total knee replacement can be a successful operation for pain relief. However, 10-34% of patients experience chronic postsurgical pain. Our aim was to synthesise evidence on the effectiveness of applying predictive models to guide preventive treatment, and for interventions in the management of chronic pain after total knee replacement. We conducted a systematic review of randomised controlled trials using appropriate search strategies in the Cochrane Library, MEDLINE and EMBASE from inception to October 2014. No language restrictions were applied. Adult patients receiving total knee replacement. Predictive models to guide treatment for prevention of chronic pain. Interventions for management of chronic pain. Reporting of specific outcomes was not an eligibility criterion but we sought outcomes relating to pain severity. No studies evaluated the effectiveness of predictive models in guiding treatment and improving outcomes after total knee replacement. One study evaluated an intervention for the management of chronic pain. The trial evaluated the use of a botulinum toxin A injection with antinociceptive and anticholinergic activity in 49 patients with chronic postsurgical pain after knee replacement. A single injection provided meaningful pain relief for about 40 days and the authors acknowledged the need for a large trial with repeated injections. No trials of multidisciplinary interventions or individualised treatments were identified. Our systematic review highlights a lack of evidence about the effectiveness of prediction and management strategies for chronic postsurgical pain after total knee replacement. As a large number of people are affected by chronic pain after total knee replacement, development of an evidence base about care for these patients should be a research priority. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain.

    PubMed

    Lomazzo, Ermelinda; Bindila, Laura; Remmers, Floor; Lerner, Raissa; Schwitter, Claudia; Hoheisel, Ulrich; Lutz, Beat

    2015-01-01

    The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We found that CUS increased anxiety- and depression-like behavior and enhanced basal nociception in mice. When co-applied with repeated NGF injections, CUS elicited a sustained long-lasting widespread hyperalgesia. In order to evaluate a potential therapeutic strategy for the treatment of chronic pain associated with stress, we hypothesized that the endocannabinoid system (ECS) may represent a target signaling system. We found that URB597, an inhibitor of the anandamide-degrading enzyme fatty acid amide hydrolase (FAAH), and JZL184, an inhibitor of the 2-arachidonoyl glycerol-degrading enzyme monoacylglycerol lipase (MAGL), increased eCB levels in the brain and periphery and were both effective in reducing CUS-induced anxiety measured by the light-dark test and CUS-induced thermal hyperalgesia. Remarkably, the long-lasting widespread hyperalgesia induced by combining CUS and NGF was effectively reduced by URB597, but not by JZL184. Simultaneous inhibition of FAAH and MAGL did not improve the overall therapeutic response. Therefore, our findings indicate that enhancement of anandamide signaling with URB597 is a promising pharmacological approach for the alleviation of chronic widespread nociception in stress-exposed mice, and thus, it could represent a potential treatment strategy for chronic pain associated with neuropsychiatric disorders in humans.

  12. Assessing the effect of chronic oedema with associated ulceration.

    PubMed

    Hunter, Megan

    2015-10-01

    Chronic oedema is a common problem in the UK and, given the country's ageing population, the numbers are predicted to rise. In an epidemiological study carried out in Derby, England, researchers found the prevalence of chronic oedema to be 3.99 in every 1000 people, with the prevalence increasing to 10.31 in those aged 65-74 years. Often, patients with untreated chronic oedema will develop an ulceration that can lead to further costs and hospital admissions. The cost of treating chronic wounds has been estimated at £2.3 billion-£3.1 billion a year. It is therefore surprising that given the number of patients living with these problems, there is still a lack of knowledge and skill among nurses when assessing patients with chronic oedema and associated ulceration. This article offers advice for nurses when assessing leg ulcers in patients with chronic oedema, detailing the visual skin changes most frequently seen in these patients. The article also discusses some of the treatment options available, briefly covering the advantages and disadvantages of each option.

  13. Triumph and tragedy: anemia management in chronic kidney disease.

    PubMed

    Novak, James E; Szczech, Lynda A

    2008-11-01

    Recent trial data have resulted in a reevaluation of the management of anemia in chronic kidney disease, including the use of erythropoiesis-stimulating agents, intravenous iron, and novel pharmaceuticals. In this review, we evaluate the latest research on anemia management in chronic kidney disease. Clinical trials of erythropoiesis-stimulating agents indicate that targeting the complete correction of anemia in patients with chronic kidney disease results in a greater risk of morbidity and mortality despite improved hemoglobin and quality of life. Conversely, intravenous iron has been found effective and relatively well tolerated in treating anemia in chronic kidney disease, even in patients with elevated ferritin. New agents to manage anemia, including long-acting erythropoietin derivatives, are also in active development. Erythropoiesis-stimulating agents should be used to target hemoglobin 11-12 g/dl in patients with chronic kidney disease. Intravenous iron may be beneficial for patients with hemoglobin less than 11 g/dl and transferrin saturation less than 25% despite elevated ferritin (500-1200 ng/ml). An upcoming placebo-controlled trial of darbepoetin should help to define the role of erythropoiesis-stimulating agents in chronic kidney disease.

  14. Managing painful chronic wounds: the Wound Pain Management Model.

    PubMed

    Price, Patricia; Fogh, Karsten; Glynn, Chris; Krasner, Diane L; Osterbrink, Jürgen; Sibbald, R Gary

    2007-04-01

    Chronic wound pain is not well understood and the literature is limited. Six of 10 patients venous leg ulcer experience pain with their ulcer, and similar trends are observed for other chronic wounds. Chronic wound pain can lead to depression and the feeling of constant tiredness. Pain related to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions of the pain experience: location, duration, intensity, quality, onset and impact on activities of daily living. Holistic management must be based on a safe and effective mix of psychosocial approaches together with local and systemic pain management. It is no longer acceptable to ignore or inadequately document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase.

  15. Endoscopic treatment of chronic radiation proctopathy.

    PubMed

    Wilson, Sydney A; Rex, Douglas K

    2006-09-01

    Chronic radiation proctopathy is a complication of pelvic radiation therapy. The acute phase of radiation injury to the rectum occurs during or up to 3 months following radiation. Acute radiation injury can continue into a chronic phase or chronic radiation proctopathy may develop after a latent period of several months or years. Symptoms associated with the condition include diarrhea, rectal pain, bleeding, tenesmus, and stricture formation. Of the various symptoms, only bleeding from radiation-induced telangiectasias is amenable to endoscopic therapy. This paper summarizes the findings of experts in the field on endoscopic treatment of bleeding from chronic radiation proctopathy. Medical management is generally ineffective in controlling bleeding from chronic radiation proctopathy. Surgical intervention has a high incidence of morbidity. Promising advances have been made in endoscopic therapy, including formalin, neodymium/yttrium aluminum garnet, argon and potassium titanyl phosphate laser treatments, as well as argon plasma coagulation. Argon plasma coagulation presents an effective, efficient, inexpensive and reasonably safe noncontact method for destruction of radiation telangiectasias. Based on currently available data and trends, argon plasma coagulation is the favored treatment for bleeding from chronic radiation proctopathy.

  16. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

    PubMed

    Larkin, Benjamin P; Glastras, Sarah J; Chen, Hui; Pollock, Carol A; Saad, Sonia

    2018-04-24

    Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD. Epigenetic modifications are changes that regulate gene expression without altering the DNA sequence. Of these, DNA methylation is the most studied. Epigenetic imprints, particularly DNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by which maternal-fetal transmission of chronic disease occurs. Our current review explores the evidence for the role of DNA methylation in the development of CKD, diabetic kidney disease, diabetes, and obesity. DNA methylation has been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agents may play a potential therapeutic role in preventing development and progression of CKD.-Larkin, B. P., Glastras, S. J., Chen, H., Pollock, C. A., Saad, S. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

  17. Associative fear learning and perceptual discrimination: a perceptual pathway in the development of chronic pain.

    PubMed

    Zaman, Jonas; Vlaeyen, Johan W S; Van Oudenhove, Lukas; Wiech, Katja; Van Diest, Ilse

    2015-04-01

    Recent neuropsychological theories emphasize the influence of maladaptive learning and memory processes on pain perception. However, the precise relationship between these processes as well as the underlying mechanisms remain poorly understood; especially the role of perceptual discrimination and its modulation by associative fear learning has received little attention so far. Experimental work with exteroceptive stimuli consistently points to effects of fear learning on perceptual discrimination acuity. In addition, clinical observations have revealed that in individuals with chronic pain perceptual discrimination is impaired, and that tactile discrimination training reduces pain. Based on these findings, we present a theoretical model of which the central tenet is that associative fear learning contributes to the development of chronic pain through impaired interoceptive and proprioceptive discrimination acuity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Developmental Trajectories of Chinese Adolescents' Relational Aggression: Associations With Changes in Social-Psychological Adjustment.

    PubMed

    Chen, Liang; Zhang, Wenxin; Ji, Linqin; Deater-Deckard, Kirby

    2018-05-25

    This study investigated the development of relational aggression (RA) in a sample of Chinese youth (N = 2,274, 52% boys) from fourth (M age  = 10.27 years) to ninth grade. Using latent class growth analysis, four trajectories were identified for both peer- and teacher-rated RA: a no aggression trajectory, a low-increasing trajectory, a moderate-decreasing trajectory, and a chronically high trajectory. Chronically high RA showed a chronicity effect on adolescent peer acceptance, rejection, and rule-breaking behaviors. Adolescents showed worse adjustment as RA increased, but they did not necessarily evidence significant improvement in adjustment even if their RA decreased. Findings reveal the maladaptive nature of RA and highlight the importance of considering cultural context in understanding RA. © 2018 Society for Research in Child Development.

  19. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis

    PubMed Central

    van der Heijden, Roel A.; Bijzet, Johan; Meijers, Wouter C.; Yakala, Gopala K.; Kleemann, Robert; Nguyen, Tri Q.; de Boer, Rudolf A.; Schalkwijk, Casper G.; Hazenberg, Bouke P. C.; Tietge, Uwe J. F.; Heeringa, Peter

    2015-01-01

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process. PMID:26563579

  20. Obesity-induced chronic inflammation in high fat diet challenged C57BL/6J mice is associated with acceleration of age-dependent renal amyloidosis.

    PubMed

    van der Heijden, Roel A; Bijzet, Johan; Meijers, Wouter C; Yakala, Gopala K; Kleemann, Robert; Nguyen, Tri Q; de Boer, Rudolf A; Schalkwijk, Casper G; Hazenberg, Bouke P C; Tietge, Uwe J F; Heeringa, Peter

    2015-11-13

    Obesity-induced inflammation presumably accelerates the development of chronic kidney diseases. However, little is known about the sequence of these inflammatory events and their contribution to renal pathology. We investigated the effects of obesity on the evolution of age-dependent renal complications in mice in conjunction with the development of renal and systemic low-grade inflammation (LGI). C57BL/6J mice susceptible to develop age-dependent sclerotic pathologies with amyloid features in the kidney, were fed low (10% lard) or high-fat diets (45% lard) for 24, 40 and 52 weeks. HFD-feeding induced overt adiposity, altered lipid and insulin homeostasis, increased systemic LGI and adipokine release. HFD-feeding also caused renal upregulation of pro-inflammatory genes, infiltrating macrophages, collagen I protein, increased urinary albumin and NGAL levels. HFD-feeding severely aggravated age-dependent structural changes in the kidney. Remarkably, enhanced amyloid deposition rather than sclerosis was observed. The degree of amyloidosis correlated significantly with body weight. Amyloid deposits stained positive for serum amyloid A (SAA) whose plasma levels were chronically elevated in HFD mice. Our data indicate obesity-induced chronic inflammation as a risk factor for the acceleration of age-dependent renal amyloidosis and functional impairment in mice, and suggest that obesity-enhanced chronic secretion of SAA may be the driving factor behind this process.

  1. Patients' Acceptance of Smartphone Health Technology for Chronic Disease Management: A Theoretical Model and Empirical Test.

    PubMed

    Dou, Kaili; Yu, Ping; Deng, Ning; Liu, Fang; Guan, YingPing; Li, Zhenye; Ji, Yumeng; Du, Ningkai; Lu, Xudong; Duan, Huilong

    2017-12-06

    Chronic disease patients often face multiple challenges from difficult comorbidities. Smartphone health technology can be used to help them manage their conditions only if they accept and use the technology. The aim of this study was to develop and test a theoretical model to predict and explain the factors influencing patients' acceptance of smartphone health technology for chronic disease management. Multiple theories and factors that may influence patients' acceptance of smartphone health technology have been reviewed. A hybrid theoretical model was built based on the technology acceptance model, dual-factor model, health belief model, and the factors identified from interviews that might influence patients' acceptance of smartphone health technology for chronic disease management. Data were collected from patient questionnaire surveys and computer log records about 157 hypertensive patients' actual use of a smartphone health app. The partial least square method was used to test the theoretical model. The model accounted for .412 of the variance in patients' intention to adopt the smartphone health technology. Intention to use accounted for .111 of the variance in actual use and had a significant weak relationship with the latter. Perceived ease of use was affected by patients' smartphone usage experience, relationship with doctor, and self-efficacy. Although without a significant effect on intention to use, perceived ease of use had a significant positive influence on perceived usefulness. Relationship with doctor and perceived health threat had significant positive effects on perceived usefulness, countering the negative influence of resistance to change. Perceived usefulness, perceived health threat, and resistance to change significantly predicted patients' intentions to use the technology. Age and gender had no significant influence on patients' acceptance of smartphone technology. The study also confirmed the positive relationship between intention to use and actual use of smartphone health apps for chronic disease management. This study developed a theoretical model to predict patients' acceptance of smartphone health technology for chronic disease management. Although resistance to change is a significant barrier to technology acceptance, careful management of doctor-patient relationship, and raising patients' awareness of the negative effect of chronic disease can negate the effect of resistance and encourage acceptance and use of smartphone health technology to support chronic disease management for patients in the community. ©Kaili Dou, Ping Yu, Ning Deng, Fang Liu, YingPing Guan, Zhenye Li, Yumeng Ji, Ningkai Du, Xudong Lu, Huilong Duan. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 06.12.2017.

  2. S-adenosyl methionine (SAM) attenuates the development of tolerance to analgesic activity of morphine in rats.

    PubMed

    Katyal, Jatinder; Kumar, Hemant; Joshi, Dinesh; Gupta, Yogendra Kumar

    2017-04-03

    Development of tolerance to analgesic effect, on chronic administration of morphine, limits its clinical usefulness in pain management. S-adenosyl methionine (SAM) used for arthritis and approved as a supplement in many countries including United States was evaluated for reducing morphine tolerance. Male 'Wistar' rats were used. The analgesic activity was determined using tail flick analgesiometer (Columbus Instruments, USA). Rats given morphine (7mg/kg), intraperitoneally (i.p.), once daily for 5days developed tolerance to analgesic effect. To evaluate the effect of SAM on morphine tolerance, SAM 800mg/kg was administered orally (p.o.), 45min prior to each dose of morphine. The analgesic activity of SAM and opioidergic component in its activity was also evaluated. Co-administration of morphine and SAM reversed morphine tolerance. SAM exhibited analgesic effect after repeated administration which was reversed by naloxone administration. Since safety of SAM on chronic use is documented it can be a good option in morphine tolerance. Role in drug addiction and withdrawal should also be evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Asthma management simulation for children: translating theory, methods, and strategies to effect behavior change.

    PubMed

    Shegog, Ross; Bartholomew, L Kay; Gold, Robert S; Pierrel, Elaine; Parcel, Guy S; Sockrider, Marianna M; Czyzewski, Danita I; Fernandez, Maria E; Berlin, Nina J; Abramson, Stuart

    2006-01-01

    Translating behavioral theories, models, and strategies to guide the development and structure of computer-based health applications is well recognized, although a continued challenge for program developers. A stepped approach to translate behavioral theory in the design of simulations to teach chronic disease management to children is described. This includes the translation steps to: 1) define target behaviors and their determinants, 2) identify theoretical methods to optimize behavioral change, and 3) choose educational strategies to effectively apply these methods and combine these into a cohesive computer-based simulation for health education. Asthma is used to exemplify a chronic health management problem and a computer-based asthma management simulation (Watch, Discover, Think and Act) that has been evaluated and shown to effect asthma self-management in children is used to exemplify the application of theory to practice. Impact and outcome evaluation studies have indicated the effectiveness of these steps in providing increased rigor and accountability, suggesting their utility for educators and developers seeking to apply simulations to enhance self-management behaviors in patients.

  4. A bio-psycho-social exercise program (RÜCKGEWINN) for chronic low back pain in rehabilitation aftercare--study protocol for a randomised controlled trial.

    PubMed

    Hentschke, Christian; Hofmann, Jana; Pfeifer, Klaus

    2010-11-17

    There is strong, internationally confirmed evidence for the short-term effectiveness of multimodal interdisciplinary specific treatment programs for chronic back pain. However, the verification of long-term sustainability of achieved effects is missing so far. For long-term improvement of pain and functional ability high intervention intensity or high volume seems to be necessary (> 100 therapy hours). Especially in chronic back pain rehabilitation, purposefully refined aftercare treatments offer the possibility to intensify positive effects or to increase their sustainability. However, quality assured goal-conscious specific aftercare programs for the rehabilitation of chronic back pain are absent. This study aims to examine the efficacy of a specially developed bio-psycho-social chronic back pain specific aftercare intervention (RÜCKGEWINN) in comparison to the current usual aftercare (IRENA) and a control group that is given an educational booklet addressing pain-conditioned functional ability and back pain episodes. Overall rehabilitation effects as well as predictors for compliance to the aftercare programs are analysed. Therefore, a multicenter prospective 3-armed randomised controlled trial is conducted. 456 participants will be consecutively enrolled in inpatient and outpatient rehabilitation and assigned to either one of the three study arms. Outcomes are measured before and after rehabilitation. Aftercare programs are assessed at ten month follow up after dismissal form rehabilitation. Special methodological and logistic challenges are to be mastered in this trial, which accrue from the interconnection of aftercare interventions to their residential district and the fact that the proportion of patients who take part in aftercare programs is low. The usability of the aftercare program is based on the transference into the routine care and is also reinforced by developed manuals with structured contents, media and material for organisation assistance as well as training manuals for therapists in the aftercare.

  5. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection

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

    Wu, Xueling; Zhang, Zhenhai; Schramm, Chaim A.

    HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here in this paper, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of themore » study period, VRC01-lineage clades showed continuous evolution, with rates of ~2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization.« less

  6. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection.

    PubMed

    Wu, Xueling; Zhang, Zhenhai; Schramm, Chaim A; Joyce, M Gordon; Kwon, Young Do; Zhou, Tongqing; Sheng, Zizhang; Zhang, Baoshan; O'Dell, Sijy; McKee, Krisha; Georgiev, Ivelin S; Chuang, Gwo-Yu; Longo, Nancy S; Lynch, Rebecca M; Saunders, Kevin O; Soto, Cinque; Srivatsan, Sanjay; Yang, Yongping; Bailer, Robert T; Louder, Mark K; Mullikin, James C; Connors, Mark; Kwong, Peter D; Mascola, John R; Shapiro, Lawrence

    2015-04-23

    HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of the study period, VRC01-lineage clades showed continuous evolution, with rates of ∼2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Sensorimotor plasticity after music-supported therapy in chronic stroke patients revealed by transcranial magnetic stimulation.

    PubMed

    Amengual, Julià L; Rojo, Nuria; Veciana de Las Heras, Misericordia; Marco-Pallarés, Josep; Grau-Sánchez, Jennifer; Schneider, Sabine; Vaquero, Lucía; Juncadella, Montserrat; Montero, Jordi; Mohammadi, Bahram; Rubio, Francisco; Rueda, Nohora; Duarte, Esther; Grau, Carles; Altenmüller, Eckart; Münte, Thomas F; Rodríguez-Fornells, Antoni

    2013-01-01

    Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

  8. Maturation and Diversity of the VRC01-Antibody Lineage over 15 Years of Chronic HIV-1 Infection

    DOE PAGES

    Wu, Xueling; Zhang, Zhenhai; Schramm, Chaim A.; ...

    2015-04-09

    HIV-1-neutralizing antibodies develop in most HIV-1-infected individuals, although highly effective antibodies are generally observed only after years of chronic infection. Here in this paper, we characterize the rate of maturation and extent of diversity for the lineage that produced the broadly neutralizing antibody VRC01 through longitudinal sampling of peripheral B cell transcripts over 15 years and co-crystal structures of lineage members. Next-generation sequencing identified VRC01-lineage transcripts, which encompassed diverse antibodies organized into distinct phylogenetic clades. Prevalent clades maintained characteristic features of antigen recognition, though each evolved binding loops and disulfides that formed distinct recognition surfaces. Over the course of themore » study period, VRC01-lineage clades showed continuous evolution, with rates of ~2 substitutions per 100 nucleotides per year, comparable to that of HIV-1 evolution. This high rate of antibody evolution provides a mechanism by which antibody lineages can achieve extraordinary diversity and, over years of chronic infection, develop effective HIV-1 neutralization.« less

  9. [Development and evaluation of a program to promote self management in patients with chronic hepatitis B].

    PubMed

    Yang, Jin-Hyang

    2012-04-01

    The purpose of this study was to identify the effects of the program to promote self management for patients with chronic hepatitis B. The research was a quasi-experimental design using a non-equivalent control group pre-post test. The participants were 61 patients, 29 in the experimental group and 32 in the control group. A pretest and 2 posttests were conducted to measure main variables. For the experimental group, the self-management program, consisting of counseling-centered activities in small groups, was given for 6 weeks. Data were analyzed using χ², t-test, and repeated measures ANOVA with PASW statistics program. There were statistically significant increases in knowledge, self-efficacy, active ways of coping, and self-management compliance but not in passive ways of coping in the experimental group compared to the control group over two different times. The results of this study indicate that the self-management program is effective in increasing knowledge, self-efficacy, active ways of coping, and self-management compliance among patients with chronic hepatitis B. Therefore, it can be usefully utilized in the field of nursing for patients with chronic disease as a nursing intervention for people with chronic hepatitis B.

  10. Exploring views on satisfaction with life in young children with chronic illness: an innovative approach to the collection of self-report data from children under 11.

    PubMed

    Christie, Deborah; Romano, Gabriella; Barnes, Jacqueline; Madge, Nicola; Nicholas, David B; Koot, Hans M; Armstrong, Daniel F; Shevlin, Mark; Kantaris, Xenya; Khatun, Hasina; Sutcliffe, Alastair G

    2012-01-01

    The objective of this study was to explore young children's views on the impact of chronic illness on their life in order to inform future development of a patient-based self-report health outcome measure. We describe an approach to facilitating self-report views from young children with chronic illness. A board game was designed in order to obtain qualitative data from 39 children with a range of chronic illness conditions and 38 healthy controls ranging in age from 3 to 11 years. The format was effective in engaging young children in a self-report process of determining satisfaction with life and identified nine domains. The board game enabled children aged 5-11 years with chronic illness to describe the effects of living with illness on home, family, friends, school and life in general. It generated direct, non-interpreted material from children who, because of their age, may have been considered unable or limited their ability to discuss and describe how they feel. Obtaining this information for children aged 4 and under continues to be a challenge.

  11. Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques.

    PubMed

    Reuben, Scott S; Buvanendran, Asokumar

    2007-06-01

    The prevalences of complex regional pain syndrome, phantom limb pain, chronic donor-site pain, and persistent pain following total joint arthroplasty are alarmingly high. Central nervous system plasticity that occurs in response to tissue injury may contribute to the development of persistent postoperative pain. Many researchers have focused on methods to prevent central neuroplastic changes from occurring through the utilization of preemptive or preventive multimodal analgesic techniques. Multimodal analgesia allows a reduction in the doses of individual drugs for postoperative pain and thus a lower prevalence of opioid-related adverse events. The rationale for this strategy is the achievement of sufficient analgesia due to the additive effects of, or the synergistic effects between, different analgesics. Effective multimodal analgesic techniques include the use of nonsteroidal anti-inflammatory drugs, local anesthetics, alpha-2 agonists, ketamine, alpha(2)-delta ligands, and opioids.

  12. Expected social utility of life time in the presence of a chronic disease.

    PubMed

    Mulder, P G; Hempenius, A L

    1993-10-01

    Interventive action aimed at reducing the incidence of an irreversible chronic noncommunicable disease in a population has various effects. Hopefully, it increases total longevity in the population and it causes the disease to develop later in time in a smaller portion of the population. In this paper a statistical model is built by which these effects can be estimated. A three dimensional probability density function that underlies this model is changed by the interventive action. It is shown how a three dimensional utility function can be defined to appropriately judge this change.

  13. [Chronic disease management: mistaken approach in the elderly].

    PubMed

    Veras, Renato Peixoto

    2012-12-01

    Lifestyle changes, including unhealthy eating habits and high rates of physical inactivity and stress, along with an increase in life expectancy have been accompanied by increasing rates of chronic non-communicable diseases. Chronic diseases are the main causes of death and disability in Brazil. Chronic disease management is one of the most important challenges facing health managers who are constantly seeking interventions and strategies to reduce costs and hospital admissions and to prevent other conditions. However, most existing models of health care have focused exclusively on disease, but it is a mistaken approach. An integrated approach is required to effectively meet patient needs. The purpose of this article was to further discuss policies and strategies for the development of new models of care for the elderly with an emphasis on prevention and resolution actions.

  14. Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. III. Acute and chronic effects of CAPs on heart rate, heart-rate fluctuation, and body temperature.

    PubMed

    Hwang, Jing-Shiang; Nadziejko, Christine; Chen, Lung Chi

    2005-04-01

    Normal mice (C57) and mice prone to develop atherosclerosis (ApoE-/-) were implanted with electrocardiograph (EKG), core body temperature, and motion transmitters were exposed daily for 6 h to Tuxedo, NY, concentrated ambient particles (CAPs) for 5 day/wk during the spring and summer of 2003. The series of 5-min EKG monitoring and body-temperature measurements were obtained for each animal in the CAPs and filtered air sham exposure groups. Our hypothesis was that chronic exposure could cause cumulative health effects. We used our recently developed nonparametric method to estimate the daily time periods that mean heart rates (HR), body temperature, and physical activity differed significantly between the CAPs and sham exposed group. CAPs exposure most affected heart rate between 1:30 a.m. and 4:30 a.m. With the response variables being the average heart rate, body temperature, and physical activity, we adopted a two-stage modeling approach to obtain the estimates of chronic and acute effects on the changes of these three response variables. In the first stage, a time-varying model estimated daily crude effects. In the second stage, the true means of the estimated crude effects were modeled with a polynominal function of time for chronic effects, a linear term of daily CAPs exposure concentrations for acute effects, and a random component for unknown noise. A Bayesian framework combined these two stages. There were significant decreasing patterns of HR, body temperature, and physical activity for the ApoE-/- mice over the 5 mo of CAPs exposure, with smaller and nonsignificant changes for the C57 mice. The chronic effect changes of the three response variables for ApoE-/- mice were maximal in the last few weeks. There was also a significant relationship between CAPs exposure concentration and short-term changes of heart rate in ApoE-/- mice during exposure. Response variables were also defined for examining fluctuations of 5-min heart rates within long (i.e., 3-6 h) and short time periods (i.e., approximately 15 min). The results for the ApoE-/- mice showed that heart-rate fluctuation within the longer periods increased to 1.35-fold by the end of exposure experiment, while the heart-rate fluctuation within 15 min decreased to 0.7-fold.

  15. Community perceptions of health and chronic disease in South Indian rural transitional communities: a qualitative study.

    PubMed

    Hayter, Arabella K M; Jeffery, Roger; Sharma, Chitra; Prost, Audrey; Kinra, Sanjay

    2015-01-01

    Chronic diseases are now the leading cause of death and disability worldwide; this epidemic has been linked to rapid economic growth and urbanisation in developing countries. Understanding how characteristics of the physical, social, and economic environment affect behaviour in the light of these changes is key to identifying successful interventions to mitigate chronic disease risk. We undertook a qualitative study consisting of nine focus group discussions (FGDs) (n=57) in five villages in rural Andhra Pradesh, South India, to understand people's perceptions of community development and urbanisation in relation to chronic disease in rural transitional communities. Specifically, we sought to understand perceptions of change linked to diet, physical activity, and pollution (because these exposures are most relevant to chronic diseases), with the aim of defining future interventions. The transcripts were analysed thematically. Participants believed their communities were currently less healthy, more polluted, less physically active, and had poorer access to nutritious food and shorter life expectancies than previously. There were contradictory perceptions of the effects of urbanisation on health within and between individuals; several of the participants felt their quality of life had been reduced. In the present study, residents viewed change and development within their villages as an inevitable and largely positive process but with some negative health consequences. Understanding how these changes are affecting populations in transitional rural areas and how people relate to their environment may be useful to guide community planning for health. Measures to educate and empower people to make healthy choices within their community may help reduce the spread of chronic disease risk factors in future years.

  16. Chronic stress sensitizes rats to pancreatitis induced by cerulein: role of TNF-α.

    PubMed

    Binker, Marcelo-G; Binker-Cosen, Andres-A; Richards, Daniel; Gaisano, Herbert-Y; de Cosen, Rodica-H; Cosen-Binker, Laura-I

    2010-11-28

    To investigate chronic stress as a susceptibility factor for developing pancreatitis, as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer. Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation. Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats. In vitro exposure of pancreatic acini to TNF-α disorganized the actin cytoskeleton. This was further increased by TNF-α/CCK treatment, which additionally reduced amylase secretion, and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner. TNF-α/CCK also enhanced caspases' activity and lactate dehydrogenase release, induced ATP loss, and augmented the ADP/ATP ratio. In vivo, rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels. Serum, pancreatic, and lung inflammatory parameters, as well as caspases'activity in pancreatic and lung tissue, were substantially enhanced in stressed/cerulein-treated rats, which also experienced tissues' ATP loss and greater ADP/ATP ratios. Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema, hemorrhage and leukocyte infiltrate, and pancreatic necrosis. Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-α-antibody, which diminished all inflammatory parameters, histopathological scores, and apoptotic/necrotic markers in stressed/cerulein-treated rats. In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation.

  17. The therapeutic potential of Na+ and Ca2+ channel blockers in pain management.

    PubMed

    Sabido-David, Cibele; Faravelli, Laura; Salvati, Patricia

    2004-10-01

    Chronic pain affects a large percentage of the population, representing a socio-economic burden. Current treatments are characterised by suboptimal efficacy and/or side effects that limit their use. Among several approaches to treating chronic pain, voltage-sensitive Ca(2+) and Na(+) channels are promising targets. This review evaluates the preclinical evidence that supports the involvement of these targets, with specific attention to those subtypes that appear more strictly correlated with pain generation and sustainment, as well as those compounds that modulate the activity of Ca(2+) and/or Na(+) channels that are currently in clinical development for chronic pain conditions.

  18. Oral chronic ethanol administration to rodents by agar gel diet.

    PubMed

    Bykov, I; Palmén, M; Piirainen, L; Lindros, K O

    2004-01-01

    Chronic ethanol administration to rodents requires specially designed equipment and is labor intensive. Here we report a new procedure. A commercial liquid diet preparation was made into a gel by addition of 0.5% agar. The gel, containing 5.3% ethanol, was offered in Falcon tubes equipped with a feeding opening. The gel consumption by C57/Bl mice resulted in high blood ethanol levels (average 43 mM). After 6 weeks, marked liver steatosis and significantly increased serum alanine aminotransferase levels had developed. Administration of ethanol in a nutritionally adequate gel provides a simple method for studies on chronic ethanol effects in rodents.

  19. The costs of chronic noise exposure for terrestrial organisms.

    PubMed

    Barber, Jesse R; Crooks, Kevin R; Fristrup, Kurt M

    2010-03-01

    Growth in transportation networks, resource extraction, motorized recreation and urban development is responsible for chronic noise exposure in most terrestrial areas, including remote wilderness sites. Increased noise levels reduce the distance and area over which acoustic signals can be perceived by animals. Here, we review a broad range of findings that indicate the potential severity of this threat to diverse taxa, and recent studies that document substantial changes in foraging and anti-predator behavior, reproductive success, density and community structure in response to noise. Effective management of protected areas must include noise assessment, and research is needed to further quantify the ecological consequences of chronic noise exposure in terrestrial environments.

  20. High volume acupuncture clinic (HVAC) for chronic knee pain--audit of a possible model for delivery of acupuncture in the National Health Service.

    PubMed

    Berkovitz, Saul; Cummings, Mike; Perrin, Chris; Ito, Rieko

    2008-03-01

    Recent research has established the efficacy, effectiveness and cost effectiveness of acupuncture for some forms of chronic musculoskeletal pain. However, there are practical problems with delivery which currently prevent its large scale implementation in the National Health Service. We have developed a delivery model at our hospital, a 'high volume' acupuncture clinic (HVAC) in which patients are treated in a group setting for single conditions using standardised or semi-standardised electroacupuncture protocols by practitioners with basic training. We discuss our experiences using this model for chronic knee pain and present an outcome audit for the first 77 patients, demonstrating satisfactory initial (eight week) clinical results. Longer term (one year) data are currently being collected and the model should next be tested in primary care to confirm its feasibility.

  1. Structured review: evaluating the effectiveness of nurse case managers in improving health outcomes in three major chronic diseases.

    PubMed

    Sutherland, Debbie; Hayter, Mark

    2009-11-01

    This paper presents the findings of a review and appraisal of the evidence for the effectiveness of nurse case management in improving health outcomes for patients living either with Diabetes, Chronic Obstructive Pulmonary Disease or Coronary Heart Disease. Long term chronic health conditions provide some of the greatest challenges to western health care systems. In the UK, three of the most significant chronic conditions are Diabetes, Chronic Obstructive Pulmonary Disease and Coronary Heart Disease. Patients with these long term conditions are high users of health services who often receive unplanned, poorly co-ordinated, ad-hoc care in response to an exacerbation or crisis. To counter this, the nurse case manager is identified as a central aspect of improving care for these patients. However, the evidence for the effectiveness of nurse case management in improving health outcomes for the chronically ill is scarce. A structured review of the literature. The review was undertaken focussing on studies that evaluated nurse case management with one or all of the three major long term chronic conditions. A total of 108 papers were initially reviewed and filtered to leave 75 citations that were appraised. About 18 papers were finally included in the review and subject to thematic analysis based on the health outcomes evaluated in the studies. Significantly positive results were reported for nurse case management impact on five health outcomes; 'objective clinical measurements', 'quality of life and functionality', 'patient satisfaction', 'adherence to treatment' and 'self care and service use'. The evidence generated in this review suggests that nurse case managers have the potential to achieve improved health outcomes for patients with long term conditions. Further research is required to support role development and create a more targeted approach to the intervention.

  2. Effects of Fuzheng Huayu 319 recipe on liver fibrosis in chronic hepatitis B

    PubMed Central

    Liu, Ping; Liu, Cheng; Xu, Lie-Ming; Hu, Yi-Yang; Xue, Hui-Ming; Liu, Cheng-Hai; Zhang, Zhi-Qing

    1998-01-01

    AIM: To investigate clinic effects of Fuzheng Huayu 319 recipe (319 recipe) on liver fibrosis in chronic hepatitis B. METHODS: Ninety-five patients with chronic hepatitis B were divide into the treated (63 cases) and control (32 cases) group, and orally administrated with 0.5g 319 capsule or 0.5g Dahuang Zhachong pill tid for 3 months, respectively. The liver functions and serological fibrotic markers were observed before and after treatment, 12 cases in the treated group were examined with liver biopsy. RESULTS: Three hundreds nineteen recipe could remarkably decreased serum ALT level and total bilirubin and significantly improve serum albumin and A/G ratio. Its effects were better than Dahuang Zhachong pill. Before treatment, patients¡äserum monamine oxidase activities, tissue inhibitor of metalloproteinase (TIMP)-1, procollagen type III and laminin were all higher than those of health peoples. These levels decreased remarkably after treatment, and urine hydroxyproline level increased significantly (P<0.001-0.05). Compared with the control, the improvement in treated group was better than that in the control except TIMP-1. According to the scoring system for staging of chronic hepatitis, the fibrotic extents of 7 cases among 12 cases examined by liver biopsy decreased remarkably (1 case decreased by 3 scores, 5 by 2 scores, 1 by 1 score). CONCLUSION: Fuzheng Huayu 319 recipe had good therapeutic effects on chronic hepatitis B, it could reverse the development of liver fibross to some extent. In general its effects were better than that of Dahuang Zhachong pill. PMID:11819318

  3. Chronic corticosterone administration effects on behavioral emotionality in female c57bl6 mice.

    PubMed

    Mekiri, Maryam; Gardier, Alain M; David, Denis J; Guilloux, Jean-Philippe

    2017-04-01

    Understanding the pathophysiology of affective disorders and their treatment relies on the availability of experimental models that mimic aspects of the disease. Most of the studies on depressive disorders are conducted with male rodents, mostly because including females in protocols is more difficult. Indeed, there is a complex series of changes in the brain of females due to the estrous cycle, adding an important variability factor to the disease. However, twice as many women as men have a lifetime diagnosis of major depressive disorder (MDD), so we need to develop reliable female models of depression to improve our understanding of this disease. Here, we describe the effects of chronic corticosterone administration (CORT) on female mice, a procedure known to enhance behavioral emotionality in male mice. A dose-response study showed that 4 weeks of CORT exposure at 35 μg/ml in the drinking water enhanced the emotionality score of female mice, but with a very small size effect. Tests of longer treatment duration failed to potentiate the behavioral effects of CORT. As some steps of adult hippocampal neurogenesis are known to be sensitive to chronic CORT exposure, cell proliferation and survival, as well as neuronal maturation in the dentate gyrus of the hippocampus, analyses revealed no effect of chronic CORT exposure in female mice. Overall, this study showed that female C57BL6 mice are insensitive to chronic CORT as a way to model anxio-depressive-like behavior. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. 76 FR 54474 - Submission for OMB Review; Comment Request New proposed collection, Biospecimen and Physical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... authorize the National Institute of Child Health and Human Development* to conduct a national longitudinal... children's health and development. (b) IN GENERAL.--The Director of the National Institute of Child Health... effects of both chronic and intermittent exposures on child health and human development; and (2...

  5. Bridging knowledge to develop an action plan for integrated care for chronic diseases in Greece

    PubMed Central

    Lionis, Christos; Yfantopoulos, John

    2015-01-01

    The health, social and economic impact of chronic diseases is well documented in Europe. However, chronic diseases threaten relatively more the ‘memorandum and peripheral’ Eurozone countries (i.e., Greece, Spain, Portugal and Ireland), which were under heavy recession after the economic crisis in 2009. Especially in Greece, where the crisis was the most severe across Europe, the austerity measures affected mainly people with chronic diseases. As a result, the urgency to tackle the threat of chronic diseases in Greece by promoting public health and providing effective chronic care while flattening the rising health care expenditure is eminent. In many European countries, integrated care is seen as a means to achieve this. The aim of this paper was to support Greek health policy makers to develop an action plan from 2015 onwards, to integrate care by bridging local policy context and needs with knowledge and experience from other European countries. To achieve this aim, we adopted a conceptual framework developed by the World Health Organization on one hand to analyse the status of integrated care in Greece, and on the other to develop an action plan for reform. The action plan was based on an analysis of the Greek health care system regarding prerequisite conditions to integrate care, a clear understanding of its context and successful examples of integrated care from other European countries. This study showed that chronic diseases are poorly addressed in Greece and integrated care is in embryonic stage. Greek policy makers have to realise that this is the opportunity to make substantial reforms in chronic care. Failing to reform towards integrated care would lead to the significant risk of collapse of the Greek health care system with all associated negative consequences. The action plan provided in this paper could support policy makers to make the first serious step to face this challenge. The details and specifications of the action plan can only be decided by Greek policy makers in close cooperation with other health and social care partners. This is the appropriate time for doing so. PMID:27118957

  6. Pain relief by transcutaneous electric nerve stimulation with bidirectional modulated sine waves in patients with chronic back pain: a randomized, double-blind, sham-controlled study.

    PubMed

    Shimoji, Koki; Takahashi, Norio; Nishio, Yasuyuki; Koyanagi, Mika; Aida, Sumihisa

    2007-01-01

    Objectives.  Newly developed bidirectional modulated sine waves (BMW) might provide some derived benefit to patients with low back pain. Pain relief by transcutaneous electric nerve stimulation (TENS) with BMWs was tested. Materials and Methods.  Analgesic effects of BMWs and conventional bidirectional pulsed waves on chronic back pain in 28 patients were compared, and effects of repeated TENS using BMWs on chronic back pain were investigated in 21 patients by means of a randomized double-blind, sham-controlled, parallel-group method. Pain intensity was assessed using numerical rating scale (NRS). Results.  There was significant immediate reduction in NRS in patients receiving BMWs, and 60 min after treatment compared to sham TENS. Weekly repeated treatments using massage and TENS with BMWs for 5 weeks resulted in a decrease of NRS, but there were no significant differences between the TENS plus massage and sham TENS plus massage groups. Conclusions.  This study shows that TENS with BMWs significantly inhibits chronic back pain, and treatment effects are attained within a day. The results also suggest that there were no statistically significant long-term effects of TENS with BMW in the repeated treatment.

  7. A review of the health impacts of barium from natural and anthropogenic exposure.

    PubMed

    Kravchenko, Julia; Darrah, Thomas H; Miller, Richard K; Lyerly, H Kim; Vengosh, Avner

    2014-08-01

    There is an increasing public awareness of the relatively new and expanded industrial barium uses which are potential sources of human exposure (e.g., a shale gas development that causes an increased awareness of environmental exposures to barium). However, absorption of barium in exposed humans and a full spectrum of its health effects, especially among chronically exposed to moderate and low doses of barium populations, remain unclear. We suggest a systematic literature review (from 1875 to 2014) on environmental distribution of barium, its bioaccumulation, and potential and proven health impacts (in animal models and humans) to provide the information that can be used for optimization of future experimental and epidemiological studies and developing of mitigative and preventive strategies to minimize negative health effects in exposed populations. The potential health effects of barium exposure are largely based on animal studies, while epidemiological data for humans, specifically for chronic low-level exposures, are sparse. The reported health effects include cardiovascular and kidney diseases, metabolic, neurological, and mental disorders. Age, race, dietary patterns, behavioral risks (e.g., smoking), use of medications (those that interfere with absorbed barium in human organism), and specific physiological status (e.g., pregnancy) can modify barium effects on human health. Identifying, evaluating, and predicting the health effects of chronic low-level and moderate-level barium exposures in humans is challenging: Future research is needed to develop an understanding of barium bioaccumulation in order to mitigate its potential health impacts in various exposured populations. Further, while occupationally exposed at-risk populations exist, it is also important to identify potentially vulnerable subgroups among non-occupationally exposed populations (e.g., elderly, pregnant women, children) who are at higher risk of barium exposure from drinking water and food.

  8. Innovative Opioid Peptides and Biased Agonism: Novel Avenues for More Effective and Safer Analgesics to Treat Chronic Pain.

    PubMed

    Bedini, Andrea; Spampinato, Santi Mario

    2017-02-15

    Chronic pain is a clinically relevant and yet unsolved conditions that is poorly treated with the currently available drugs, thus highlighting the urgent need of innovative analgesics. Although opiates are not very effective in the treatment of inflammatory and neuropathic pain, developing novel opioid receptor peptide agonists, as well as modulating the opioid receptor-mediated responses in a ligand-specific fashion, may represent an innovative and promising strategy to identify more efficacious and safer antalgic drugs. In this review, novel analogues of endomorphin 1 (a mu opioid receptor selective agonist able to induce analgesia in different animal models of pain - including neuropathic pain) and dermorphin (one of the most potent opioid peptide existing in nature) will be discussed as they are emerging as a promising starting point to develop novel opioid agonists: endomorphin 1 analogues, in fact, may determine antinociception in different models of neuropathic pain with reduced side effects as compared to classic opiates as morphine; dermorphin analogues may elicit analgesia in animal models of both inflammatory and neuropathic pain and with less severe adverse effects. Furthermore, such opioid peptides may allow to explore unprecedented modalities of ligand-receptor interactions, helping to characterize biased agonism at opioid receptors: exploiting functional selectivity at opioid receptor may lead to identify innovative analgesic with improved pharmacological responses and optimized side effects. Thus, innovative opioid peptides, as those outlined in this review, are promising candidates to develop more effective opioid analgesics to be employed as medications for chronic pain states, as inflammatory or neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. "I can be happy even when I lose the game": the influence of chronic regulatory focus and primed self-construal on exergamers' mood.

    PubMed

    Jin, Seung-A Annie

    2010-08-01

    This research explored the effects of priming interdependent self-construals (collective self ) versus independent self-construals (private self ) on exergame players' mood in response to negative performance feedback. An experiment was conducted to test the interaction effects of self-construal priming as a situational factor and game players' chronic regulatory focus as an individual difference factor. To this end, the author leveraged a video-game console (Wii) and an exergame (Dance Dance Revolution) in a controlled, randomized 2 x 2 (experimental priming: interdependent self-construal vs. independent self-construal x game players' chronic promotion regulatory focus: low vs. high) between-subjects factorial design experiment (N = 58). The results of a two-way analysis of variance demonstrated the proposed interaction effect between primed self-construal and game players' chronic regulatory focus on the game players' mood in response to negative performance. The theoretical mechanism underlying the two-way interaction is explicated by regulatory focus and the primed self-construals is explicated by regulatory focus theory and two-basket theory. Practical implications for game developers and theoretical contributions to video-game research are discussed.

  10. Effectiveness of finger-equipped electrode (FEE)-triggered electrical stimulation improving chronic stroke patients with severe hemiplegia.

    PubMed

    Inobe, Jun-ichi; Kato, Takashi

    2013-01-01

    Electric stimulation (ES) has been recognized as an effective method to improve motor function to paralysed patients with stroke. It is important for ES to synchronize with voluntary movement. To enhance this co-ordination, the finger-equipped electrode (FEE) was developed. The purpose of this study was to evaluate FEE in improving motor function of upper extremities (UEs) in patients with chronic stroke. The study participants included four patients with chronic stroke who received FEE electronic stimulation (FEE-ES) plus passive and active training and three control patients who underwent training without FEE-ES. The patients were treated five times weekly for 4 weeks. UE motor function was evaluated before and after treatment using Fugl-Meyer Assessment (FMA) and Brunnstrom recovery staging. The mean age of patients in each group was 60-years and there was a mean of 49 months since the onset of symptoms. All patients had severe UE weakness. The patients receiving FEE-ES had greater improvement in UE function than control patients (total, proximal and distal FMA, p < 0.05; Brunnstrom staging of UE, p < 0.05). The results indicate that FEE-ES may be an effective treatment for patients with chronic stroke.

  11. Antinociceptive effects of oxymatrine from Sophora flavescens, through regulation of NR2B-containing NMDA receptor-ERK/CREB signaling in a mice model of neuropathic pain.

    PubMed

    Wang, Haiyan; Li, Yuxiang; Dun, Linglu; Xu, Yaqiong; Jin, Shaojv; Du, Juan; Ma, Lin; Li, Juan; Zhou, Ru; He, Xiaoliang; Sun, Tao; Yu, Jianqiang

    2013-08-15

    In this study we investigated antinociceptive effects of oxymatrine through regulation of NR2B-containing NMDA receptor-ERK/CREB signaling in a chronic neuropathic pain model induced by chronic constrictive injury (CCI) of the sciatic nerve. The von Frey and plantar tests were performed to assess the degree of mechanical and thermal changes respectively. Immunohistochemistry assay was used to evaluate the expressions of NR2B. Western blotting assay were used to evaluate the expressions of NR2B, tERK, p-ERK, tCREB and p-CREB. The intraperitoneal administration of OMT (160, 80 mg/kg) could prevent the development of mechanical allodynia, thermal hyperalgesia induced by CCI. Intraperitoneal administration of OMT decreased the mean IOD of NR2B in the dorsal horn and expression of NR2B, p-ERK and p-CREB protein. Regulation of NMDA NR2B receptor-ERK/CREB signaling maybe the targets for the antinociceptive effects of OMT on a chronic neuropathic pain model induced by chronic constrictive injury of the sciatic nerve. Copyright © 2013 Elsevier GmbH. All rights reserved.

  12. Bone architecture adaptations after spinal cord injury: impact of long-term vibration of a constrained lower limb.

    PubMed

    Dudley-Javoroski, S; Petrie, M A; McHenry, C L; Amelon, R E; Saha, P K; Shields, R K

    2016-03-01

    This study examined the effect of a controlled dose of vibration upon bone density and architecture in people with spinal cord injury (who eventually develop severe osteoporosis). Very sensitive computed tomography (CT) imaging revealed no effect of vibration after 12 months, but other doses of vibration may still be useful to test. The purposes of this report were to determine the effect of a controlled dose of vibratory mechanical input upon individual trabecular bone regions in people with chronic spinal cord injury (SCI) and to examine the longitudinal bone architecture changes in both the acute and chronic state of SCI. Participants with SCI received unilateral vibration of the constrained lower limb segment while sitting in a wheelchair (0.6g, 30 Hz, 20 min, three times weekly). The opposite limb served as a control. Bone mineral density (BMD) and trabecular micro-architecture were measured with high-resolution multi-detector CT. For comparison, one participant was studied from the acute (0.14 year) to the chronic state (2.7 years). Twelve months of vibration training did not yield adaptations of BMD or trabecular micro-architecture for the distal tibia or the distal femur. BMD and trabecular network length continued to decline at several distal femur sub-regions, contrary to previous reports suggesting a "steady state" of bone in chronic SCI. In the participant followed from acute to chronic SCI, BMD and architecture decline varied systematically across different anatomical segments of the tibia and femur. This study supports that vibration training, using this study's dose parameters, is not an effective anti-osteoporosis intervention for people with chronic SCI. Using a high-spatial-resolution CT methodology and segmental analysis, we illustrate novel longitudinal changes in bone that occur after spinal cord injury.

  13. Development and application of the adverse outcome pathway framework for understanding and predicting chronic toxicity: II. A focus on growth impairment in fish.

    PubMed

    Groh, Ksenia J; Carvalho, Raquel N; Chipman, James K; Denslow, Nancy D; Halder, Marlies; Murphy, Cheryl A; Roelofs, Dick; Rolaki, Alexandra; Schirmer, Kristin; Watanabe, Karen H

    2015-02-01

    Adverse outcome pathways (AOPs) organize knowledge on the progression of toxicity through levels of biological organization. By determining the linkages between toxicity events at different levels, AOPs lay the foundation for mechanism-based alternative testing approaches to hazard assessment. Here, we focus on growth impairment in fish to illustrate the initial stages in the process of AOP development for chronic toxicity outcomes. Growth is an apical endpoint commonly assessed in chronic toxicity tests for which a replacement is desirable. Based on several criteria, we identified reduction in food intake to be a suitable key event for initiation of middle-out AOP development. To start exploring the upstream and downstream links of this key event, we developed three AOP case studies, for pyrethroids, selective serotonin reuptake inhibitors (SSRIs) and cadmium. Our analysis showed that the effect of pyrethroids and SSRIs on food intake is strongly linked to growth impairment, while cadmium causes a reduction in growth due to increased metabolic demands rather than changes in food intake. Locomotion impairment by pyrethroids is strongly linked to their effects on food intake and growth, while for SSRIs their direct influence on appetite may play a more important role. We further discuss which alternative tests could be used to inform on the predictive key events identified in the case studies. In conclusion, our work demonstrates how the AOP concept can be used in practice to assess critically the knowledge available for specific chronic toxicity cases and to identify existing knowledge gaps and potential alternative tests. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Influence of collaterals on the left ventricular end-diastolic pressure and serum NT-proBNP levels in patients with coronary chronic total occlusion.

    PubMed

    Samadov, Fuad; Yesildag, Osman; Sari, Ibrahim; Atas, Halil; Akhundova, Aysel; Basaran, Yelda

    2017-06-01

    Although numerous studies have shown the protective effects of the well-developed coronary collaterals on left ventricular functions, the relationship between collateral grade and left ventricular end diastolic pressure has not been studied in chronic total occlusion patients. Also, there are conflicting data on the effect of collaterals on NT-proBNP levels. The aim of our study was to evaluate the relationship between coronary collateral circulation and left ventricular end diastolic pressure and NT-proBNP levels in chronic total occlusion patients. Study group was retrospectively selected from the patients who had undergone coronary angiography at our hospital between June 2011 and March 2013. Clinical, biochemical, angiographic and hemodynamic data of 199 consecutive patients having at least one totally occluded major epicardial coronary artery were evaluated. Coronary collateral circulation was graded according to Rentrop classification. While Rentrop grade 3 was defined as well-developed, all the remaining collateral grades were regarded as poor collaterals. Overall 87 patients were found to have good collaterals and 112 patients had poor collaterals. There was no significant difference between the patients with well- or poorly developed coronary collaterals with regard to left ventricular end diastolic pressure (16.84 ± 5.40 mmHg vs 16.10 ± 6.09, respectively, p  = 0,632) and log NT-proBNP (2.46 ± 0.58 vs 2.59 ± 0.76, respectively, p  = 0,335). In patients with coronary chronic total occlusion even well-developed coronary collaterals are not capable of protecting the rise of left ventricular end diastolic pressure and NT-proBNP levels which are reliable markers of the left ventricular dysfunction.

  15. Chronic neurodegenerative consequences of traumatic brain injury.

    PubMed

    Chauhan, Neelima B

    2014-01-01

    Traumatic brain injury (TBI) is a serious public health concern and a major cause of death and disability worldwide. Each year, an estimated 1.7 million Americans sustain TBI of which ~52,000 people die, ~275,000 people are hospitalized and 1,365,000 people are treated as emergency outpatients. Currently there are ~5.3 million Americans living with TBI. TBI is more of a disease process than of an event that is associated with immediate and long-term sensomotor, psychological and cognitive impairments. TBI is the best known established epigenetic risk factor for later development of neurodegenerative diseases and dementia. People sustaining TBI are ~4 times more likely to develop dementia at a later stage than people without TBI. Single brain injury is linked to later development of symptoms resembling Alzheimer's disease while repetitive brain injuries are linked to later development of chronic traumatic encephalopathy (CTE) and/or Dementia Pugilistica (DP). Furthermore, genetic background of ß-amyloid precursor protein (APP), Apolipoprotein E (ApoE), presenilin (PS) and neprilysin (NEP) genes is associated with exacerbation of neurodegenerative process after TBI. This review encompasses acute effects and chronic neurodegenerative consequences after TBI.

  16. SKF83959 Produces Antidepressant Effects in a Chronic Social Defeat Stress Model of Depression through BDNF-TrkB Pathway

    PubMed Central

    Jiang, Bo; Wang, Fang; Yang, Si; Fang, Peng; Deng, Zhi-Fang; Xiao, Jun-Li; Hu, Zhuang-Li

    2015-01-01

    Background: SKF83959 stimulates the phospholipase Cβ/inositol phosphate 3 pathway, resulting in the activation of Ca2+/calmodulin-dependent kinase IIα, which affects the synthesis of brain-derived neurotrophic factor, a neurotrophic factor critical for the pathophysiology of depression. Previous reports showed that SKF83959 elicited antidepressant activity in the forced swim test and tail suspension test as a novel triple reuptake inhibitor. However, there are no studies showing the effects of SKF83959 in a chronic stress model of depression and the role of phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway in SKF83959-mediated antidepressant effects. Methods: In this study, SKF83959 was firstly investigated in the chronic social defeat stress model of depression. The changes in hippocampal neurogenesis, dendrite spine density, and brain-derived neurotrophic factor signaling pathway after chronic social defeat stress and SKF83959 treatment were then investigated. Pharmacological inhibitors and small interfering RNA/short hairpin RNA methods were further used to explore the antidepressive mechanisms of SKF83959. Results: We found that SKF83959 produced antidepressant effects in the chronic social defeat stress model and also restored the chronic social defeat stress-induced decrease in hippocampal brain-derived neurotrophic factor signaling pathway, dendritic spine density, and neurogenesis. By using various inhibitors and siRNA/shRNA methods, we further demonstrated that the hippocampal dopamine D5 receptor, phospholipase C/inositol phosphate 3/ calmodulin-dependent kinase IIα pathway, and brain-derived neurotrophic factor system are all necessary for the SKF83959 effects. Conclusion: These results suggest that SKF83959 can be developed as a novel antidepressant and produces antidepressant effects via the hippocampal D5/ phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway. PMID:25522427

  17. Genotoxic effects of high dose rate X-ray and low dose rate gamma radiation in ApcMin/+ mice.

    PubMed

    Graupner, Anne; Eide, Dag M; Brede, Dag A; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H; Bouffler, Simon D; Brunborg, Gunnar; Olsen, Ann Karin

    2017-10-01

    Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc +/+ (wild type) and Apc Min/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60 Co-γ-rays at a LDR (2.2 mGy h -1 ) or acutely exposed to 2.6 Gy HDR X-rays (1.3 Gy min -1 ). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig-a gene mutation assay), and levels of DNA lesions (Comet assay, single-strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3- and 10-fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The Apc Min/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560-569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

  18. Genotoxic effects of high dose rate X‐ray and low dose rate gamma radiation in ApcMin/+ mice

    PubMed Central

    Eide, Dag M.; Brede, Dag A.; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H.; Bouffler, Simon D.; Brunborg, Gunnar; Olsen, Ann Karin

    2017-01-01

    Risk estimates for radiation‐induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc+/+ (wild type) and ApcMin/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60Co‐γ‐rays at a LDR (2.2 mGy h−1) or acutely exposed to 2.6 Gy HDR X‐rays (1.3 Gy min−1). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig‐a gene mutation assay), and levels of DNA lesions (Comet assay, single‐strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3‐ and 10‐fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The ApcMin/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560–569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:28856770

  19. Acute and chronic toxicity of nickel to rainbow trout (Oncorhynchus mykiss).

    PubMed

    Brix, Kevin V; Keithly, James; DeForest, David K; Laughlin, Jim

    2004-09-01

    Of the fish species tested in chronic Ni exposures, rainbow trout (Oncorhynchus mykiss) is the most sensitive. To develop additional Ni toxicity data and to investigate the toxic mode of action for Ni, we conducted acute (96-h) and chronic (85-d early life-stage) flow-through studies using rainbow trout. In addition to standard toxicological endpoints, we investigated the effects of Ni on ionoregulatory physiology (Na, Ca, and Mg). The acute median lethal concentration for Ni was 20.8 mg/L, and the 24-h gill median lethal accumulation was 666 nmol/g wet weight. No effects on plasma Ca, Mg, or Na were observed during acute exposure. In the chronic study, no significant effects on embryo survival, swim-up, hatching, or fingerling survival or growth were observed at dissolved Ni concentrations up to 466 microg/L, the highest concentration tested. This concentration is considerably higher than the only other reported chronic no-observed-effect concentration (<33 microg/L) for rainbow trout. Accumulation of Ni in trout eggs indicates the chorion is only a partial barrier with 36%, 63%, and 1% of total accumulated Ni associated with the chorion, yolk, and embryo, respectively. Whole-egg ion concentrations were reduced by Ni exposure. However, most of this reduction occurred in the chorion rather than in the embryos, and no effects on hatching success or larval survival were observed as a result. Plasma ion concentrations measured in swim-up fingerlings at the end of the chronic-exposure period were not significantly reduced by exposure to Ni. Nickel accumulated on the gill in an exponential manner but plateaued in trout plasma at waterborne Ni concentrations of 118 microg/L or greater. Consistent with previous studies, Ni did not appear to disrupt ionoregulation in acute exposures of rainbow trout. Our results also suggest that Ni is not an ionoregulatory toxicant in long-term exposures, but the lack of effects in the highest Ni treatment precludes a definitive conclusion.

  20. Linker phosphorylation of Smad3 promotes fibro-carcinogenesis in chronic viral hepatitis of hepatocellular carcinoma

    PubMed Central

    Murata, Miki; Yoshida, Katsunori; Yamaguchi, Takashi; Matsuzaki, Koichi

    2014-01-01

    Epidemiological and clinical data point to a close association between chronic hepatitis B virus infection or chronic hepatitis C virus infection and development of hepatocellular carcinoma (HCC). HCC develops over several decades and is associated with fibrosis. This sequence suggests that persistent viral infection and chronic inflammation can synergistically induce liver fibrosis and hepatocarcinogenesis. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in diverse cellular processes and contributes to hepatic fibro-carcinogenesis under inflammatory microenvironments during chronic liver diseases. The biological activities of TGF-β are initiated by the binding of the ligand to TGF-β receptors, which phosphorylate Smad proteins. TGF-β type I receptor activates Smad3 to create COOH-terminally phosphorylated Smad3 (pSmad3C), while pro-inflammatory cytokine-activated kinases phosphorylates Smad3 to create the linker phosphorylated Smad3 (pSmad3L). During chronic liver disease progression, virus components, together with pro-inflammatory cytokines and somatic mutations, convert the Smad3 signal from tumor-suppressive pSmad3C to fibro-carcinogenic pSmad3L pathways, accelerating liver fibrosis and increasing the risk of HCC. The understanding of Smad3 phosphorylation profiles may provide new opportunities for effective chemoprevention and personalized therapy for patients with hepatitis virus-related HCC in the future. PMID:25386050

  1. "I Love Fruit But I Can't Afford It": Using Participatory Action Research to Develop Community-Based Initiatives to Mitigate Challenges to Chronic Disease Management in an African American Community Living in Public Housing.

    PubMed

    Rogers, Courtney; Johnson, Joy; Nueslein, Brianne; Edmunds, David; Valdez, Rupa S

    2018-03-12

    As chronic conditions are on the rise in the USA, management initiatives outside of the inpatient setting should be explored to reduce associated cost and access disparities. Chronic conditions disproportionately affect African American public housing residents due to the effects of historical marginalization on the manifestation of economic and social problems exacerbating health disparities and outcomes. Informed by participatory research action tenets, this study focused on identifying the challenges to management of chronic conditions and developing community-envisioned initiatives to address these challenges in a predominantly African American public housing community. Two focus groups were conducted with former and current public housing residents and were analyzed using inductive content analysis. Physical activity, the cost associated with healthy eating, and lack of information were noted as challenges to chronic disease management. Initiatives discussed were the formation of a walking partner's program to promote physical activity, a shopper's club to exchange coupons and learn how to prepare healthy meals, and a natural remedy's book to share information intergenerationally about management tactics. Challenges identified existed predominantly on the individual and the system level, while the initiatives generated target engaging interpersonal and community relationships. These community-envisioned approaches should be explored to facilitate chronic disease management in public housing neighborhoods.

  2. [Effects of a Multi-disciplinary Approached, Empowerment Theory Based Self-management Intervention in Older Adults with Chronic Illness].

    PubMed

    Park, Chorong; Song, Misoon; Cho, Belong; Lim, Jaeyoung; Song, Wook; Chang, Heekyung; Park, Yeon-Hwan

    2015-04-01

    The purpose of this study was to develop a multi-disciplinary self-management intervention based on empowerment theory and to evaluate the effectiveness of the intervention for older adults with chronic illness. A randomized controlled trial design was used with 43 Korean older adults with chronic illness (Experimental group=22, Control group=21). The intervention consisted of two phases: (1) 8-week multi-disciplinary, team guided, group-based health education, exercise session, and individual empowerment counseling, (2) 16-week self-help group activities including weekly exercise and group discussion to maintain acquired self-management skills and problem-solving skills. Baseline, 8-week, and 24-week assessments measured health empowerment, exercise self-efficacy, physical activity, and physical function. Health empowerment, physical activity, and physical function in the experimental group increased significantly compared to the control group over time. Exercise self-efficacy significantly increased in experimental group over time but there was no significant difference between the two groups. The self-management program based on empowerment theory improved health empowerment, physical activity, and physical function in older adults. The study finding suggests that a health empowerment strategy may be an effective approach for older adults with multiple chronic illnesses in terms of achieving a sense of control over their chronic illness and actively engaging self-management.

  3. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study.

    PubMed

    Grachev, I D; Fredrickson, B E; Apkarian, A V

    2000-12-15

    The neurobiology of chronic pain, including chronic back pain, is unknown. Structural imaging studies of the spine cannot explain all cases of chronic back pain. Functional brain imaging studies indicate that the brain activation patterns are different between chronic pain patients and normal subjects, and the thalamus, and prefrontal and cingulate cortices are involved in some types of chronic pain. Animal models of chronic pain suggest abnormal spinal cord chemistry. Does chronic pain cause brain chemistry changes? We examined brain chemistry changes in patients with chronic back pain using in vivo single- voxel proton magnetic resonance spectroscopy ((1)H-MRS). In vivo (1)H-MRS was used to measure relative concentrations of N-acetyl aspartate, creatine, choline, glutamate, glutamine, gamma-aminobutyric acid, inositol, glucose and lactate in relation to the concentration of creatine. These measurements were performed in six brain regions of nine chronic low back pain patients and 11 normal volunteers. All chronic back pain subjects underwent clinical evaluation and perceptual measures of pain and anxiety. We show that chronic back pain alters the human brain chemistry. Reductions of N-acetyl aspartate and glucose were demonstrated in the dorsolateral prefrontal cortex. Cingulate, sensorimotor, and other brain regions showed no chemical concentration differences. In chronic back pain, the interrelationship between chemicals within and across brain regions was abnormal, and there was a specific relationship between regional chemicals and perceptual measures of pain and anxiety. These findings provide direct evidence of abnormal brain chemistry in chronic back pain, which may be useful in diagnosis and future development of more effective pharmacological treatments.

  4. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor.

    PubMed

    Taliaz, Dekel; Loya, Assaf; Gersner, Roman; Haramati, Sharon; Chen, Alon; Zangen, Abraham

    2011-03-23

    Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

  5. The MNK–eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain

    PubMed Central

    Asiedu, Marina N.; Megat, Salim; Burton, Michael D.; Burgos-Vega, Carolina C.; Melemedjian, Ohannes K.; Boitano, Scott; Vagner, Josef; Pancrazio, Joseph J.; Mogil, Jeffrey S.; Dussor, Gregory

    2017-01-01

    Injury-induced sensitization of nociceptors contributes to pain states and the development of chronic pain. Inhibiting activity-dependent mRNA translation through mechanistic target of rapamycin and mitogen-activated protein kinase (MAPK) pathways blocks the development of nociceptor sensitization. These pathways convergently signal to the eukaryotic translation initiation factor (eIF) 4F complex to regulate the sensitization of nociceptors, but the details of this process are ill defined. Here we investigated the hypothesis that phosphorylation of the 5′ cap-binding protein eIF4E by its specific kinase MAPK interacting kinases (MNKs) 1/2 is a key factor in nociceptor sensitization and the development of chronic pain. Phosphorylation of ser209 on eIF4E regulates the translation of a subset of mRNAs. We show that pronociceptive and inflammatory factors, such as nerve growth factor (NGF), interleukin-6 (IL-6), and carrageenan, produce decreased mechanical and thermal hypersensitivity, decreased affective pain behaviors, and strongly reduced hyperalgesic priming in mice lacking eIF4E phosphorylation (eIF4ES209A). Tests were done in both sexes, and no sex differences were found. Moreover, in patch-clamp electrophysiology and Ca2+ imaging experiments on dorsal root ganglion neurons, NGF- and IL-6-induced increases in excitability were attenuated in neurons from eIF4ES209A mice. These effects were recapitulated in Mnk1/2−/− mice and with the MNK1/2 inhibitor cercosporamide. We also find that cold hypersensitivity induced by peripheral nerve injury is reduced in eIF4ES209A and Mnk1/2−/− mice and following cercosporamide treatment. Our findings demonstrate that the MNK1/2–eIF4E signaling axis is an important contributing factor to mechanisms of nociceptor plasticity and the development of chronic pain. SIGNIFICANCE STATEMENT Chronic pain is a debilitating disease affecting approximately one in three Americans. Chronic pain is thought to be driven by changes in the excitability of peripheral nociceptive neurons, but the precise mechanisms controlling these changes are not elucidated. Emerging evidence demonstrates that mRNA translation regulation pathways are key factors in changes in nociceptor excitability. Our work demonstrates that a single phosphorylation site on the 5′ cap-binding protein eIF4E is a critical mechanism for changes in nociceptor excitability that drive the development of chronic pain. We reveal a new mechanistic target for the development of a chronic pain state and propose that targeting the upstream kinase, MAPK interacting kinase 1/2, could be used as a therapeutic approach for chronic pain. PMID:28674170

  6. Nanoparticle-mediated endothelial cell-selective delivery of pitavastatin induces functional collateral arteries (therapeutic arteriogenesis) in a rabbit model of chronic hind limb ischemia.

    PubMed

    Oda, Shinichiro; Nagahama, Ryoji; Nakano, Kaku; Matoba, Tetsuya; Kubo, Mitsuki; Sunagawa, Kenji; Tominaga, Ryuji; Egashira, Kensuke

    2010-08-01

    We recently demonstrated in a murine model that nanoparticle-mediated delivery of pitavastatin into vascular endothelial cells effectively increased therapeutic neovascularization. For the development of a clinically applicable approach, further investigations are necessary to assess whether this novel system can induce the development of collateral arteries (arteriogenesis) in a chronic ischemia setting in larger animals. Chronic hind limb ischemia was induced in rabbits. They were administered single injections of nanoparticles loaded with pitavastatin (0.05, 0.15, and 0.5 mg/kg) into ischemic muscle. Treatment with pitavastatin nanoparticles (0.5 mg/kg), but not other nanoparticles, induced angiographically visible arteriogenesis. The effects of intramuscular injections of phosphate-buffered saline, fluorescein isothiocyanate (FITC)-loaded nanoparticles, pitavastatin (0.5 mg/kg), or pitavastatin (0.5 mg/kg) nanoparticles were examined. FITC nanoparticles were detected mainly in endothelial cells of the ischemic muscles for up to 4 weeks. Treatment with pitavastatin nanoparticles, but not other treatments, induced therapeutic arteriogenesis and ameliorated exercise-induced ischemia, suggesting the development of functional collateral arteries. Pretreatment with nanoparticles loaded with vatalanib, a vascular endothelial growth factor receptor (VEGF) tyrosine kinase inhibitor, abrogated the therapeutic effects of pitavastatin nanoparticles. Separate experiments with mice deficient for VEGF receptor tyrosine kinase demonstrated a crucial role of VEGF receptor signals in the therapeutic angiogenic effects. The nanotechnology platform assessed in this study (nanoparticle-mediated endothelial cell-selective delivery of pitavastatin) may be developed as a clinically feasible and promising strategy for therapeutic arteriogenesis in patients. Copyright (c) 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  7. Lifestyle in progression from hypertensive disorders of pregnancy to chronic hypertension in Nurses' Health Study II: observational cohort study.

    PubMed

    Timpka, Simon; Stuart, Jennifer J; Tanz, Lauren J; Rimm, Eric B; Franks, Paul W; Rich-Edwards, Janet W

    2017-07-12

    Objectives  To study the association between lifestyle risk factors and chronic hypertension by history of hypertensive disorders of pregnancy (HDP: gestational hypertension and pre-eclampsia) and investigate the extent to which these risk factors modify the association between HDP and chronic hypertension. Design  Prospective cohort study. Setting  Nurses' Health Study II (1991-2013). Participants  54 588 parous women aged 32 to 59 years with data on reproductive history and without previous chronic hypertension, stroke, or myocardial infarction. Main outcome measure  Chronic hypertension diagnosed by a physician and indicated through nurse participant self report. Multivariable Cox proportional hazards models were used to investigate the development of chronic hypertension contingent on history of HDP and four lifestyle risk factors: post-pregnancy body mass index, physical activity, adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, and dietary sodium/potassium intake. Potential effect modification (interaction) between each lifestyle factor and previous HDP was evaluated with the relative excess risk due to interaction. Results  10% (n=5520) of women had a history of HDP at baseline. 13 971 cases of chronic hypertension occurred during 689 988 person years of follow-up. Being overweight or obese was the only lifestyle factor consistently associated with higher risk of chronic hypertension. Higher body mass index, in particular, also increased the risk of chronic hypertension associated with history of HDP (relative excess risk due to interaction P<0.01 for all age strata). For example, in women aged 40-49 years with previous HDP and obesity class I (body mass index 30.0-34.9), 25% (95% confidence interval 12% to 37%) of the risk of chronic hypertension was attributable to a potential effect of obesity that was specific to women with previous HDP. There was no clear evidence of effect modification by physical activity, DASH diet, or sodium/potassium intake on the association between HDP and chronic hypertension. Conclusion  This study suggests that the risk of chronic hypertension after HDP might be markedly reduced by adherence to a beneficial lifestyle. Compared with women without a history of HDP, keeping a healthy weight seems to be especially important with such a history.

  8. Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations.

    PubMed

    Taylor, Ann M; Phillips, Kristine; Patel, Kushang V; Turk, Dennis C; Dworkin, Robert H; Beaton, Dorcas; Clauw, Daniel J; Gignac, Monique A M; Markman, John D; Williams, David A; Bujanover, Shay; Burke, Laurie B; Carr, Daniel B; Choy, Ernest H; Conaghan, Philip G; Cowan, Penney; Farrar, John T; Freeman, Roy; Gewandter, Jennifer; Gilron, Ian; Goli, Veeraindar; Gover, Tony D; Haddox, J David; Kerns, Robert D; Kopecky, Ernest A; Lee, David A; Malamut, Richard; Mease, Philip; Rappaport, Bob A; Simon, Lee S; Singh, Jasvinder A; Smith, Shannon M; Strand, Vibeke; Tugwell, Peter; Vanhove, Gertrude F; Veasley, Christin; Walco, Gary A; Wasan, Ajay D; Witter, James

    2016-09-01

    Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.

  9. Effect of Cold Preservation on Chronic Rejection in a Rat Hindlimb Transplantation Model.

    PubMed

    Bonastre, Jorge; Landín, Luis; Bolado, Pedro; Casado-Sánchez, César; López-Collazo, Eduardo; Díez, Jesús

    2016-09-01

    Previous studies on solid organ transplantation have shown that cold ischemia contributes to the development of chronic allograft vasculopathy. The authors evaluated the effect of cold ischemia on the development of chronic rejection in vascularized composite allotransplantation. Thirty rat hindlimbs were transplanted and divided into two experimental groups: immediate transplantation and transplantation after 7 hours of cold ischemia. The animals received daily low-dose immunosuppression with cyclosporine A for 2 months. Intimal proliferation, arterial permeability rate, leukocyte infiltration, and tissue fibrosis were assessed. The CD3, CD4, CD8, CD20, and CD68 cells per microscopic field (200×) were counted, and C4d deposition was investigated. Cytokine RNA analysis was performed to measure tumor necrosis factor-α, interleukin-6, and interleukin-10 levels. Significant differences were found in the intimal proliferation and arterial permeability rate between the two groups (p = 0.004). The arterial permeability rate worsened in the most distal and small vessels (p = 0.047). The numbers of CD3, CD8, CD20, and CD68 were also statistically higher in the cold ischemia group (p < 0.05, all levels). A trend toward significance was observed with C4d deposition (p = 0.059). No differences were found in the RNA of cytokines. An association between cold ischemia and chronic rejection was observed in experimental vascularized composite allotransplantation. Chronic rejection intensity and distal progression were significantly related with cold ischemia. The leukocyte infiltrates in vascularized composite allotransplantation components were a rejection marker; however, their exact implication in monitoring and their relation with cold ischemia are yet to be clarified.

  10. Effects of Acute and Chronic Treatments with Dopamine D2 and D3 Receptor Ligands on Cocaine versus Food Choice in Rats.

    PubMed

    Thomsen, Morgane; Barrett, Andrew C; Butler, Paul; Negus, S Stevens; Caine, S Barak

    2017-07-01

    Dopamine D 3 receptor ligands are potential medications for psychostimulant addiction. Medication assessment may benefit from preclinical studies that evaluate chronic medication effects on choice between an abused drug and an alternative, nondrug reinforcer. This study compared acute and chronic effects of dopamine D 2 - and D 3 -preferring ligands on choice between intravenous cocaine and palatable food in rats. Under baseline conditions, cocaine maintained dose-dependent increases in cocaine choice and reciprocal decreases in food choice. Acutely, the D 2 agonist R -(-)-norpropylapomorphine (NPA) and antagonist L-741,626 [3-[[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1 H -indole] produced leftward and rightward shifts in cocaine dose-effect curves, respectively, whereas the partial agonist terguride had no effect. All three drugs dose-dependently decreased food-maintained responding. Chronically, the effects of R -(-)-norpropylapomorphine and L-741,626 on cocaine self-administration showed marked tolerance, whereas suppression of food-reinforced behavior persisted. Acute effects of the D 3 ligands were less systematic and most consistent with nonselective decreases in cocaine- and food-maintained responding. Chronically, the D 3 agonist PF-592,379 [5-[(2 R ,5 S )-5-methyl-4-propylmorpholin-2-yl]pyridin-2-amine] increased cocaine choice, whereas an intermediate dose of the D 3 antagonist PG01037 [ N -[( E )-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]but-2-enyl]-4-pyridin-2-ylbenzamide] produced a therapeutically desirable decrease in cocaine choice early in treatment; however, tolerance to this effect developed, and lower and higher doses were ineffective. D 3 ligands failed to significantly modify total cocaine intake but caused persistent decreases in food intake. Thus, D 2 -and D 3 -preferring ligands showed distinct profiles, consistent with different pharmacological actions. In addition, these results highlight the role of acute versus chronic treatment as a determinant of test drug effects. With the possible exception of the D 3 antagonist PG01037, no ligand was promising in terms of cocaine addiction treatment. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Use of radiotelemetry to evaluate respiratory depression produced by chronic methadone administration.

    PubMed

    Lewanowitsch, Tanya; White, Jason M; Irvine, Rodney J

    2004-01-26

    Illicit and therapeutic opioid administration can result in overdose due to opioid-induced respiratory depression. Research investigating the respiratory depressant effects of opioids has been limited due to difficulties associated with acquiring long-term respiratory data. This study examined the novel use of radiotelemetry to measure respiratory rate, heart rate, locomotor activity and blood pressure in rats treated chronically with methadone. Over 4 days of treatment, respiratory rate decreased, but partial tolerance appeared to develop during active (night) periods. Decreased heart rate was observed during the night periods and tolerance appeared to develop to this effect. Activity and blood pressure did not change with treatment. The effects of naloxone hydrochloride and naloxone methiodide administration on the methadone-treated rats were also examined and both antagonists increased respiratory rate and heart rate, with only naloxone hydrochloride producing significant increases in activity. Radiotelemetry offers a means of evaluating drug effects on respiratory rate continually in ambulatory, unstressed animals.

  12. Time-course of neurodegeneration and memory impairment following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats.

    PubMed

    Pereira, Francine Martins; Ferreira, Emilene Dias Fiuza; de Oliveira, Rúbia Maria Weffort; Milani, Humberto

    2012-04-15

    The present work extends previous studies with the aim of developing the 4-vessel occlusion/internal carotid artery (4-VO/ICA) model of chronic cerebral hypoperfusion. The permanent occlusion of the vertebral arteries (VAs) and internal carotid arteries (ICAs) followed the sequence VA→ICA→ICA. The interstage interval (ISI, →), chronicity of 4-VO/ICA, and age of the animals may determine the success of the model with regard to neurohistological and behavioral outcomes. Using middle-aged rats, the present study evaluated (i) how brain damage evolves as the ISI is reduced and duration (i.e., "chronicity") of 4-VO/ICA is prolonged and (ii) how the duration of 4-VO/ICA affects retrograde memory performance. Male Wistar rats (12-15 months of age) were subjected to 4-VO/ICA with an ISI of 7, 5, 4, or 3 days, and hippocampal and cortical damage was examined 7, 30, and 90 days later. Using an ISI of 4 days, retrograde memory performance was assessed in the aversive radial maze after 4-VO/ICA with a duration of 7, 30, and 90 days. The severity of brain neurodegeneration and rate of mortality progressively increased as the ISI length decreased from 7 to 3 days, an effect that was not significantly altered by the chronicity of 4-VO/ICA. Permanent 4-VO/ICA effectively caused retrograde amnesia, an effect that worsened as the chronicity of 4-VO/ICA was prolonged. The findings confirm and expand the notion that permanent, 3-stage 4-VO/ICA effectively produces extensive neurodegeneration and persistent learning/memory impairment in middle-aged rats and that the ISI length, more than the chronicity of 4-VO/ICA, determines the final results. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Dronabinol and chronic pain: importance of mechanistic considerations.

    PubMed

    de Vries, Marjan; van Rijckevorsel, Dagmar C M; Wilder-Smith, Oliver H G; van Goor, Harry

    2014-08-01

    Although medicinal cannabis has been used for many centuries, the therapeutic potential of delta-9-tetrahydrocannabinol (Δ9-THC; international non-proprietary name = dronabinol) in current pain management remains unclear. Several pharmaceutical products with defined natural or synthesized Δ9-THC content have been developed, resulting in increasing numbers of clinical trials investigating the analgesic efficacy of dronabinol in various pain conditions. Different underlying pain mechanisms, including sensitization of nociceptive sensory pathways and alterations in cognitive and autonomic processing, might explain the varying analgesic effects of dronabinol in chronic pain states. The pharmacokinetics, pharmacodynamics and mechanisms of action of products with a defined dronabinol content are summarized. Additionally, randomized clinical trials investigating the analgesic efficacy of pharmaceutical cannabis based products are reviewed for the treatment of chronic nonmalignant pain. We suggest a mechanism-based approach beyond measurement of subjective pain relief to evaluate the therapeutic potential of dronabinol in chronic pain management. Development of objective mechanistic diagnostic biomarkers reflecting altered sensory and cognitive processing in the brain is essential to evaluate dronabinol induced analgesia, and to permit identification of responders and/or non-responders to dronabinol treatment.

  14. Sulfur Mustard Research—Strategies for the Development of Improved Medical Therapy

    PubMed Central

    Kehe, Kai; Balszuweit, Frank; Emmler, Judith; Kreppel, Helmut; Jochum, Marianne; Thiermann, Horst

    2008-01-01

    Objective: Sulfur mustard (SM) is a bifunctional alkylating substance being used as chemical warfare agent (vesicant). It is still regarded as a significant threat in chemical warfare and terrorism. Exposure to SM produces cutaneous blisters, respiratory and gastrointestinal tract injury, eye lesions, and bone marrow depression. Victims of World War I as well as those of the Iran-Iraq war have suffered from devastating chronic health impairment. Even decades after exposure, severe long-term effects like chronic obstructive lung disease, lung fibrosis, recurrent corneal ulcer disease, chronic conjunctivitis, abnormal pigmentation of the skin, and different forms of cancer have been diagnosed. Methods: This review briefly summarizes the scientific literature and own results concerning detection, organ toxicity of SM, its proposed toxicodynamic actions, and strategies for the development of improved medical therapy. Results: Despite extensive research efforts during the last century, efficient antidotes against SM have not yet been generated because its mechanism of action is not fully understood. However, deeper insights into these mechanisms gained in the last decade and promising developments of new drugs now offer new chances to minimize SM-induced organ damage and late effects. Conclusion: Polymerase inhibitors, anti-inflammatory drugs, antioxidants, matrix metalloproteinase inhibitors, and probably regulators of DNA damage repair are identified as promising approaches to improve treatment. PMID:18615149

  15. The need for geriatric dental education in India: the geriatric health challenges of the millennium.

    PubMed

    Thomas, Susan

    2013-06-01

    The rapid growth in the elderly population in a developing country such as India poses social and financial challenges by causing a shift towards non-communicable diseases and increases in chronic diseases. The economic impact of the burden of chronic diseases such as cardiovascular disease, hypertension, diabetes and cancer are high. The link between oral health and general health are particularly pronounced in older populations and impairs their quality of life. This paper reveals that in order to address the increasing health challenges and demands of a growing geriatric population, undergraduates and graduate students in dental schools should be given comprehensive or holistic health assessment training. Cost-effective modern educational strategies and educational tools such as problem-based learning will help to overcome the dearth of trained faculty in geriatric dentistry. Multidisciplinary health-care approaches and extended health-care team work are of vital importance to older patients who could benefit physically and psychologically from more efficient dental treatment. With often more than one chronic disease affecting individuals and use of polypharmacy, there is a need to increase overall knowledge of geriatric pharmacy and geriatric medicine. Measures to help older people remain healthy and active are a necessity in developing countries such as India for effective social and economic development. © 2013 FDI World Dental Federation.

  16. Physicochemical properties of dietary phytochemicals can predict their passive absorption in the human small intestine.

    PubMed

    Selby-Pham, Sophie N B; Miller, Rosalind B; Howell, Kate; Dunshea, Frank; Bennett, Louise E

    2017-05-16

    A diet high in phytochemical-rich plant foods is associated with reducing the risk of chronic diseases such as cardiovascular and neurodegenerative diseases, obesity, diabetes and cancer. Oxidative stress and inflammation (OSI) is the common component underlying these chronic diseases. Whilst the positive health effects of phytochemicals and their metabolites have been demonstrated to regulate OSI, the timing and absorption for best effect is not well understood. We developed a model to predict the time to achieve maximal plasma concentration (T max ) of phytochemicals in fruits and vegetables. We used a training dataset containing 67 dietary phytochemicals from 31 clinical studies to develop the model and validated the model using three independent datasets comprising a total of 108 dietary phytochemicals and 98 pharmaceutical compounds. The developed model based on dietary intake forms and the physicochemical properties lipophilicity and molecular mass accurately predicts T max of dietary phytochemicals and pharmaceutical compounds over a broad range of chemical classes. This is the first direct model to predict T max of dietary phytochemicals in the human body. The model informs the clinical dosing frequency for optimising uptake and sustained presence of dietary phytochemicals in circulation, to maximise their bio-efficacy for positively affect human health and managing OSI in chronic diseases.

  17. Pulmonary hypertension associated with thalassemia syndromes

    PubMed Central

    Fraidenburg, Dustin R.; Machado, Roberto F.

    2016-01-01

    Chronic hemolytic anemia has increasingly been identified as an important risk factor for the development of pulmonary hypertension. Within the thalassemia syndromes, there are multiple mechanisms, both distinct and overlapping, by which pulmonary hypertension develops and that differ among β-thalassemia major or intermedia patients. Pulmonary hypertension in β-thalassemia major correlates with the severity of hemolysis, yet in patients whose disease is well treated with chronic transfusion therapy, the development of pulmonary hypertension can be related to cardiac dysfunction and the subsequent toxic effects of iron overload rather than hemolysis. β-thalassemia intermedia, on the other hand, has a higher incidence of pulmonary hypertension owing to the low level of hemolysis that exists over years without the requirement for frequent transfusions, while splenectomy is shown to play an important role in both types. Standard therapies such as chronic transfusion have been shown to mitigate pulmonary hypertension, and appropriate chelation therapy can avoid the toxic effects of iron overload, yet is not indicated in many patients. Limited evidence exists for the use of pulmonary vasodilators or other therapies, such as l-carnitine, to treat pulmonary hypertension associated with thalassemia. Here we review the most recent findings regarding the pathogenic mechanisms, epidemiology, presentation, diagnosis, and treatment of pulmonary hypertension in thalassemia syndromes. PMID:27008311

  18. The selective reversible FAAH inhibitor, SSR411298, restores the development of maladaptive behaviors to acute and chronic stress in rodents.

    PubMed

    Griebel, Guy; Stemmelin, Jeanne; Lopez-Grancha, Mati; Fauchey, Valérie; Slowinski, Franck; Pichat, Philippe; Dargazanli, Gihad; Abouabdellah, Ahmed; Cohen, Caroline; Bergis, Olivier E

    2018-02-05

    Enhancing endogenous cannabinoid (eCB) signaling has been considered as a potential strategy for the treatment of stress-related conditions. Fatty acid amide hydrolase (FAAH) represents the primary degradation enzyme of the eCB anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). This study describes a potent reversible FAAH inhibitor, SSR411298. The drug acts as a selective inhibitor of FAAH, which potently increases hippocampal levels of AEA, OEA and PEA in mice. Despite elevating eCB levels, SSR411298 did not mimic the interoceptive state or produce the behavioral side-effects (memory deficit and motor impairment) evoked by direct-acting cannabinoids. When SSR411298 was tested in models of anxiety, it only exerted clear anxiolytic-like effects under highly aversive conditions following exposure to a traumatic event, such as in the mouse defense test battery and social defeat procedure. Results from experiments in models of depression showed that SSR411298 produced robust antidepressant-like activity in the rat forced-swimming test and in the mouse chronic mild stress model, restoring notably the development of inadequate coping responses to chronic stress. This preclinical profile positions SSR411298 as a promising drug candidate to treat diseases such as post-traumatic stress disorder, which involves the development of maladaptive behaviors.

  19. Involvement of inflammatory factors in pancreatic carcinogenesis and preventive effects of anti-inflammatory agents.

    PubMed

    Takahashi, Mami; Mutoh, Michihiro; Ishigamori, Rikako; Fujii, Gen; Imai, Toshio

    2013-03-01

    Chronic inflammation is known to be a risk for many cancers, including pancreatic cancer. Heavy alcohol drinking and cigarette smoking are major causes of pancreatitis, and epidemiological studies have shown that smoking and chronic pancreatitis are risk factors for pancreatic cancer. Meanwhile, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are elevated in pancreatitis and pancreatic cancer tissues in humans and in animal models. Selective inhibitors of iNOS and COX-2 suppress pancreatic cancer development in a chemical carcinogenesis model of hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). In addition, hyperlipidemia, obesity, and type II diabetes are also suggested to be associated with chronic inflammation in the pancreas and involved in pancreatic cancer development. We have shown that a high-fat diet increased pancreatic cancer development in BOP-treated hamsters, along with aggravation of hyperlipidemia, severe fatty infiltration, and increased expression of adipokines and inflammatory factors in the pancreas. Of note, fatty pancreas has been observed in obese and/or diabetic cases in humans. Preventive effects of anti-hyperlipidemic/anti-diabetic agents on pancreatic cancer have also been shown in humans and animals. Taking this evidence into consideration, modulation of inflammatory factors by anti-inflammatory agents will provide useful data for prevention of pancreatic cancer.

  20. Effects of a Web-based intervention for adults with chronic conditions on patient activation: online randomized controlled trial.

    PubMed

    Solomon, Michael; Wagner, Stephen L; Goes, James

    2012-02-21

    With almost one-half of Americans projected to have at least one chronic condition before 2020, a vital role of the health care system is to develop informed, engaged individuals who are effective self-managers of their health. Self-management interventions (SMIs) delivered face-to-face or by telephone (traditional SMIs) are associated with improved self-management knowledge, skills, and self-efficacy, which are expressed by the composite construct of patient activation, a predictor of health outcomes. Web-based interventions to support self-management across the spectrum of chronic diseases have the potential to reach a broader population of patients for extended periods than do traditional SMIs. However, evidence of the effectiveness of Web-based interventions on patient activation is sparse. High-quality studies featuring controlled comparisons of patients with different chronic conditions are needed to explore the interaction of Web-based interventions and patient activation. To explore the effect of a Web-based intervention on the patient activation levels of patients with chronic health conditions, measured as attitudes toward knowledge, skills, and confidence in self-managing health. For this 12-week study, prospective participants were selected from the patient panel of a regional health care system in the United States. The 201 eligible participants were randomly assigned to two groups. Intervention group participants had access to MyHealth Online, a patient portal featuring interactive health applications accessible via the Internet. Control participants had access to a health education website featuring various topics. Patient activation was assessed pre- and posttest using the 13-item patient activation measure. Parametric statistical models (t test, analysis of variance, analysis of covariance) were applied to draw inferences. The Web-based intervention demonstrated a positive and significant effect on the patient activation levels of participants in the intervention group. A significant difference in posttest patient activation scores was found between the two groups (F(1,123) = 4.438, P = .04, r = .196). Patients starting at the most advanced development of patient activation (stage 4) in the intervention group did not demonstrate significant change compared with participants beginning at earlier stages. To our knowledge, this is the first study to measure change in patient activation when a Web-based intervention is used by patients living with different chronic conditions. Results suggest that Web-based interventions increase patient activation and have the potential to enhance the self-management capabilities of the growing population of chronically ill people. Activated patients are more likely to adhere to recommended health care practices, which in turn leads to improved health outcomes. Designing Web-based interventions to target a specific stage of patient activation may optimize their effectiveness. For Web-based interventions to reach their potential as a key component of chronic disease management, evidence is needed that this technology produces benefits for a sustained period among a diverse population.

  1. Chronic pain during pregnancy: a review of the literature

    PubMed Central

    Ray-Griffith, Shona L; Wendel, Michael P; Stowe, Zachary N; Magann, Everett F

    2018-01-01

    Background and purpose The majority of the reviews and studies on chronic pain in pregnancy have primarily focused on the pharmacological and non-pharmacological treatment options. The purpose of our review was to identify evidence-based clinical research for the evaluation and management of preexisting chronic pain in pregnancy, chronic pain associated with pregnancy, and chronic pain in relation to mode of delivery. Methods A literature search was undertaken using the search engines PubMed, CINAHL, EBSCOhost, and Web of Science. Search terms used included “chronic pain” AND “pregnant OR pregnancy” OR “pregnancy complications” from inception through August 2016. Results The basis of this review was the 144 articles that met inclusion criteria for this review. Based on our review of the current literature, we recommend 7 guidelines for chronic pain management during and after pregnancy: 1) complete history and physical examination; 2) monitor patients for alcohol, nicotine, and substance use; 3) collaborate with patient to set treatment goals; 4) develop a management plan; 5) for opioids, use lowest effective dose; 6) formulate a pain management plan for labor and delivery; and 7) discuss reproductive health with women with chronic pain. Conclusion The management of chronic pain associated with pregnancy is understudied. Obstetrical providers primarily manage chronic pain during pregnancy. Some general guidelines are provided for those health care providers until more information is available. PMID:29692634

  2. Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review).

    PubMed

    Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M; Wilks, Martin F; Spandidos, Demetrios A; Fenga, Concettina

    2016-10-01

    Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well‑designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases.

  3. Occupational and environmental exposure to pesticides and cytokine pathways in chronic diseases (Review)

    PubMed Central

    Gangemi, Silvia; Gofita, Eliza; Costa, Chiara; Teodoro, Michele; Briguglio, Giusi; Nikitovic, Dragana; Tzanakakis, George; Tsatsakis, Aristides M.; Wilks, Martin F.; Spandidos, Demetrios A.; Fenga, Concettina

    2016-01-01

    Pesticides can exert numerous effects on human health as a consequence of both environmental and occupational exposures. The available knowledge base suggests that exposure to pesticides may result in detrimental reproductive changes, neurological dysfunction and several chronic disorders, which are defined by slow evolution and long-term duration. Moreover, an ever increasing amount of data have identified an association between exposure to pesticides and the harmful effects on the immune system. The real impact of alterations in humoral cytokine levels on human health, in particular in the case of chronic diseases, is still unclear. To date, studies have suggested that although exposure to pesticides can affect the immune system functionally, the development of immune disorders depends on the dose and duration of exposure to pesticides. However, many of the respective studies exhibit limitations, such as a lack of information on exposure levels, differences in the pesticide administration procedures, difficulty in characterizing a prognostic significance to the weak modifications often observed and the interpretation of obtained results. The main challenge is not just to understand the role of individual pesticides and their combinations, but also to determine the manner and the duration of exposure, as the toxic effects on the immune system cannot be separated from these considerations. There is a clear need for more well-designed and standardized epidemiological and experimental studies to recognize the exact association between exposure levels and toxic effects and to identify useful biomarkers of exposure. This review focuses on and critically discusses the immunotoxicity of pesticides and the impact of cytokine levels on health, focusing on the development of several chronic diseases. PMID:27600395

  4. Evidence for the effects of yogurt on gut health and obesity.

    PubMed

    Pei, Ruisong; Martin, Derek A; DiMarco, Diana M; Bolling, Bradley W

    2017-05-24

    Obesity is associated with increased risk for chronic diseases, and affects both developed and developing nations. Yogurt is a nutrient-dense food that may benefit individuals with lactose intolerance, constipation and diarrheal diseases, hypertension, cardiovascular diseases, diabetes, and certain types of cancer. Emerging evidence suggests that yogurt consumption might also improve the health of obese individuals. Obesity is often accompanied by chronic, low-grade inflammation perpetuated by adipose tissue and the gut. In the gut, obesity-associated dysregulation of microbiota and impaired gut barrier function may increase endotoxin exposure. Intestinal barrier function can be compromised by pathogens, inflammatory cytokines, endocannabinoids, diet, exercise, and gastrointestinal peptides. Yogurt consumption may improve gut health and reduce chronic inflammation by enhancing innate and adaptive immune responses, intestinal barrier function, lipid profiles, and by regulating appetite. While this evidence suggests that yogurt consumption is beneficial for obese individuals, randomized-controlled trials are needed to further support this hypothesis.

  5. Effects of weightlessness on the development of the vestibular apparatus and ocular nystagmus in the rat

    NASA Technical Reports Server (NTRS)

    Clark, D. L.

    1972-01-01

    The chronic 2g centrifuge was constructed for testing weightlessness effects on development of vestibular apparatus and ocular nystagmus in the rat. Both the stationary and rotating rail tests were performed. A physiological review is presented on vestibular apparatus, along with a system analysis. Time constants and input threshold level of the system are also considered.

  6. An Evaluation of the Chronic Effects of Endocrine Disrupting Chemical 4-tert-octylphenol using Japanese Medaka in a Multigenerational Test

    EPA Science Inventory

    The USEPA seeks to assess the potential effects of chemicals on populations of fish. For many of these chemicals there is little information regarding their potential to produce effects on reproduction and reproductive development through two full generations. To facilitate and...

  7. Targeting Epigenetic Mechanisms in Pain Due to Trauma and Traumatic Brain Injury (TBI)

    DTIC Science & Technology

    2015-10-01

    particularly likely to involve TBI, peripheral trauma or both. Disability due to pain and other causes is very high amongst such patients. We have no...effective approaches to reducing the likelihood of developing chronic pain after TBI or peripheral injuries, and the mechanisms supporting such pain...brain or peripheral trauma may support chronic pain. Our work to-date has established a rodent model of TBI in combination with injury to a limb as a

  8. Dynamic body weight and body composition changes in response to subordination stress.

    PubMed

    Tamashiro, Kellie L K; Hegeman, Maria A; Nguyen, Mary M N; Melhorn, Susan J; Ma, Li Yun; Woods, Stephen C; Sakai, Randall R

    2007-07-24

    Social stress is prevalent in many facets of modern society. Epidemiological data suggest that stress is linked to the development of overweight, obesity and metabolic disease. Although there are strong associations between the incidence of obesity with stress and elevated levels of hormones such as cortisol, there are limited animal models to allow investigation of the etiology of increased adiposity resulting from exposure to stress. Perhaps more importantly, an animal model that mirrors the consequences of stress in humans will provide a vehicle to develop rational clinical therapy to treat or prevent adverse outcomes from exposure to chronic social stress. In the visible burrow system (VBS) model of chronic social stress mixed gender colonies are housed for 2 week periods during which male rats of the colony quickly develop a dominance hierarchy. We found that social stress has significant effects on body weight and body composition such that subordinate rats progressively develop characteristics of obesity that occurs, in part, through neuroendocrine alterations and changes in food intake amount. Although subordinate rats are hyperphagic following social stress they do not increase their intake of sucrose solution as control and dominants do suggesting that they are anhedonic. Consumption of a high fat diet does not appear to affect development of a social hierarchy and appears to enhance the effect that chronic stress has on body composition. The visible burrow system (VBS) model of social stress may be a potential laboratory model for studying stress-associated metabolic disease, including the metabolic syndrome.

  9. National Priority Setting of Clinical Practice Guidelines Development for Chronic Disease Management.

    PubMed

    Jo, Heui-Sug; Kim, Dong Ik; Oh, Moo-Kyung

    2015-12-01

    By November 2013, a total of 125 clinical practice guidelines (CPGs) have been developed in Korea. However, despite the high burden of diseases and the clinical importance of CPGs, most chronic diseases do not have available CPGs. Merely 83 CPGs are related to chronic diseases, and only 40 guidelines had been developed in the last 5 yr. Considering the rate of the production of new evidence in medicine and the worsening burden from chronic diseases, the need for developing CPGs for more chronic diseases is becoming increasingly pressing. Since 2011, the Korean Academy of Medical Sciences and the Korea Centers for Disease Control and Prevention have been jointly developing CPGs for chronic diseases. However, priorities have to be set and resources need to be allocated within the constraint of a limited funding. This study identifies the chronic diseases that should be prioritized for the development of CPGs in Korea. Through an objective assessment by using the analytic hierarchy process and a subjective assessment with a survey of expert opinion, high priorities were placed on ischemic heart disease, cerebrovascular diseases, Alzheimer's disease and other dementias, osteoarthritis, neck pain, chronic kidney disease, and cirrhosis of the liver.

  10. Brain development of the preterm neonate after neonatal hydrocortisone treatment for chronic lung disease

    PubMed Central

    Benders, Manon J. N. L.; Groenendaal, Floris; van Bel, Frank; Vinh, Russia Ha; Dubois, Jessica; Lazeyras, François; Warfield, Simon K.; Hüppi, Petra S.; de Vries, Linda S.

    2015-01-01

    Previous studies reported impaired cerebral cortical gray matter development and neurodevelopmental impairment following neonatal dexamethasone treatment for chronic lung disease in preterm newborns. No long-term effects on neurocognitive outcome have yet been shown for hydrocortisone treatment. A prospective study was performed to evaluate brain growth at term in preterm infants who did receive neonatal hydrocortisone for chronic lung disease. Thirty-eight preterm infants (n=19 hydrocortisone, n=19 controls) were matched for gestational age at birth. Gestational age and birth weight were 27.0±1.4 vs. 27.6±1.1 weeks (p=ns), and 826±173 vs. 1017±202 gram respectively (p<0.05). Infants were studied at term equivalent age. Hydrocortisone was started with a dose of 5 mg/kg/day for 1 week, followed by a tapering course over 3 weeks. A 3D-MRI technique was used to quantify cerebral tissue volumes: cortical grey matter, basal ganglia/thalami, unmyelinated white matter, myelinated white matter, cerebellum, and cerebrospinal fluid. Infants who were treated with hydrocortisone had more severe respiratory distress. There were no differences in cerebral tissue volumes between the 2 groups at term equivalent age. In conclusion, no effect on brain growth, measured at term equivalent age, was shown following treatment with hydrocortisone for chronic lung disease. PMID:19851225

  11. Development and course of chronic pain over four years in the general population: The HUNT pain study.

    PubMed

    Landmark, Tormod; Dale, Ola; Romundstad, Pål; Woodhouse, Astrid; Kaasa, Stein; Borchgrevink, Petter C

    2018-05-13

    Epidemiological studies of chronic pain frequently report high prevalence estimates. However, there is little information about the development and natural course of chronic pain. We followed a random sample of participants from a population-based study (HUNT 3) with annual measures over four years. Among those without chronic pain at baseline, the probability of developing moderate to severe chronic pain (cumulative incidence) during the first year was 5%, a pain status that was maintained among 38% at the second follow-up. The probability of developing chronic pain diminished substantially for those who maintained a status of no chronic pain over several years. Subjects with moderate to severe chronic pain at baseline had an 8% probability of recovery into no chronic pain, a status that was maintained for 52% on the second follow-up. The probability of recovery diminished substantially as a status of chronic pain was prolonged for several years. Pain severity, widespread pain, pain catastrophizing, depression and sleep were significant predictors of future moderate to severe chronic pain, both among subjects with and without chronic pain at baseline. These findings suggest that the prognosis is fairly good after a new onset of chronic pain. When the pain has lasted for several years, the prognosis becomes poor. The same social and psychological factors predict new onset and the prognosis of chronic pain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Chronic subjective dizziness versus conversion disorder: discussion of clinical findings and rehabilitation.

    PubMed

    Honaker, Julie A; Gilbert, Jane M; Staab, Jeffrey P

    2010-06-01

    Audiologists frequently encounter patients who complain of chronic dizziness or imbalance, in the absence of active vestibular or neurological deficits. Knowledge about conditions that cause this clinical presentation will allow audiologists to make important contributions to accurate diagnosis and effective management of these patients. This article reviews 2 such conditions, chronic subjective dizziness (CSD) and conversion disorder. A case of CSD and another of conversion disorder are presented, with a literature review of their clinical presentations, key diagnostic features, and treatment strategies. The role of the audiologist in assessing patients with these conditions and facilitating appropriate treatment referrals is discussed. The audiologist is in a key position to identify individuals with CSD and conversion disorder, 2 conditions that can be effectively managed if properly recognized. The authors demonstrate an effective team approach program that includes the audiologist's contribution to differential diagnosis, education of patients and other clinicians about these conditions, and development of recommendations for neurological, psychiatric, otologic, and physical therapy referrals.

  13. Long-Term Effects Produced by Small Doses of Radioactive Substances in Chronical Experiment); OTDALENNYE POSLEDSTVIYA PORAZHENIYA MALYMI DOZAMI RADIOAKTIVNYKH VESHCHESTV V KHRONICHESKOM EKSPERIMENTE

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

    Burykina, L.N.; Zakutinskii, D.I.; Kraevskii, N.A.

    Data on the long-term effects produced by radioactive substances administered to dogs, rabbits, and rats in various ways, both in single and repeated doses, are reported. The animals were studied for three years or longer. Three successive phases were found in the chronic irradiation disease caused by the introduction of radioactive substances: the stimulation phase characterized by an instability and variability of clinical symptoms (blood picture, cardio- vascular system, and the physiological system); the phase of apparent compensation when all the symptoms are restored to normal, although changes are recorded in the reactivity of various systems of the organism whenmore » functional loads are applied; and the phase when symptoms, typical of the chronic stage of radiation disease, develop. The blastomogenous effects of radioactive substances was given special attention. Pre-tumor changes in the bone was also studied. (J.S.R.)« less

  14. The Impact of Traumatic Brain Injury on Later Life: Effects on Normal Aging and Neurodegenerative Diseases.

    PubMed

    Griesbach, Grace S; Masel, Brent E; Helvie, Richard E; Ashley, Mark J

    2018-01-01

    The acute and chronic effects of traumatic brain injury (TBI) have been widely described; however, there is limited knowledge on how a TBI sustained during early adulthood or mid-adulthood will influence aging. Epidemiological studies have explored whether TBI poses a risk for dementia and other neurodegenerative diseases associated with aging. We will discuss the influence of TBI and resulting medical comorbidities such as endocrine, sleep, and inflammatory disturbances on age-related gray and white matter changes and cognitive decline. Post mortem studies examining amyloid, tau, and other proteins will be discussed within the context of neurodegenerative diseases and chronic traumatic encephalopathy. The data support the suggestion that pathological changes triggered by an earlier TBI will have an influence on normal aging processes and will interact with neurodegenerative disease processes rather than the development of a specific disease, such as Alzheimer's or Parkinson's. Chronic neurophysiologic change after TBI may have detrimental effects on neurodegenerative disease.

  15. Systems approaches for chronic disease prevention: sound logic and empirical evidence, but is this view shared outside of academia?

    PubMed

    Wutzke, Sonia; Morrice, Emily; Benton, Murray; Wilson, Andrew

    2016-07-15

    There is a need and desire to improve chronic disease prevention efforts across Australia. Increasingly, scientists are urging the use of systems thinking and its methods to significantly shift the way we think about, and intervene in, chronic diseases. This research aimed to examine the convergence between the systems science literature and the views of those working in and advocating for prevention, in relation to the value of systems thinking and its methods for the prevention of chronic diseases. Individual and small-group semistructured interviews were undertaken with 29 individuals across Australia. The interviewees reflected a diverse cross-section of senior public health managers and program implementation staff from state and territory health departments, and senior thought leaders and public health advocates. Interviews were audio recorded and coded into key themes. Feedback from informants illustrated that, among those working in and advocating for prevention, there is a mix of support for systems thinking for chronic disease prevention, and some healthy scepticism. The lack of consistent confluence between those promoting the value of systems science, and those responsible for working in and advocating for prevention indicates a level of confusion about language and definitions. It also reflects a desire for published evidence about systems methods that have proven effectiveness. Systems thinking and its methods have a promising and important role to play in creating a robust, effective and sustainable strategy for prevention of chronic diseases throughout Australia. However, the method requires further development and refinement, and promotion of case studies of effectiveness. We also need to heed lessons learnt overseas.

  16. Effective behavioral intervention strategies using mobile health applications for chronic disease management: a systematic review.

    PubMed

    Lee, Jung-Ah; Choi, Mona; Lee, Sang A; Jiang, Natalie

    2018-02-20

    Mobile health (mHealth) has continuously been used as a method in behavioral research to improve self-management in patients with chronic diseases. However, the evidence of its effectiveness in chronic disease management in the adult population is still lacking. We conducted a systematic review to examine the effectiveness of mHealth interventions on process measures as well as health outcomes in randomized controlled trials (RCTs) to improve chronic disease management. Relevant randomized controlled studies that were published between January 2005 and March 2016 were searched in six databases: PubMed, CINAHL, EMBASE, the Cochrane Library, PsycINFO, and Web of Science. The inclusion criteria were RCTs that conducted an intervention using mobile devices such as smartphones or tablets for adult patients with chronic diseases to examine disease management or health promotion. Of the 12 RCTs reviewed, 10 of the mHealth interventions demonstrated statistically significant improvement in some health outcomes. The most common features of mHealth systems used in the reviewed RCTs were real-time or regular basis symptom assessments, pre-programed reminders, or feedbacks tailored specifically to the data provided by participants via mHealth devices. Most studies developed their own mHealth systems including mobile apps. Training of mHealth systems was provided to participants in person or through paper-based instructions. None of the studies reported the relationship between health outcomes and patient engagement levels on the mHealth system. Findings from mHealth intervention studies for chronic disease management have shown promising aspects, particularly in improving self-management and some health outcomes.

  17. Acute and Chronic Kidney Injury in a Non-Human Primate Model of Partial-Body Irradiation with Bone Marrow Sparing.

    PubMed

    Cohen, Eric P; Hankey, Kim G; Bennett, Alexander W; Farese, Ann M; Parker, George A; MacVittie, Thomas J

    2017-12-01

    The development of medical countermeasures against acute and delayed multi-organ injury requires animal models predictive of the human response to radiation and its treatment. Late chronic injury is a well-known feature of radiation nephropathy, but acute kidney injury has not been reported in an appropriate animal model. We have established a single-fraction partial-body irradiation model with minimal marrow sparing in non-human primates. Subject-based medical management was used including parenteral fluids according to prospective morbidity criteria. We show herein that 10 or 11 Gy exposures caused both acute and chronic kidney injury. Acute and chronic kidney injury appear to be dose-independent between 10 and 11 Gy. Acute kidney injury was identified during the first 50 days postirradiation and appeared to resolve before the occurrence of chronic kidney injury, which was progressively more severe up to 180 days postirradiation, which was the end of the study. These findings show that mitigation of the acute radiation syndrome by medical management will unmask delayed late effects that occur months after partial-body irradiation. They further emphasize that both acute and chronic changes in kidney function must be taken into account in the use and timing of mitigators and medical management for acute radiation syndrome and delayed effects of acute radiation exposure (DEARE).

  18. Can maternal DHA supplementation offer long-term protection against neonatal hyperoxic lung injury?

    PubMed

    Lingappan, Krithika; Moorthy, Bhagavatula

    2015-12-15

    The effect of adverse perinatal environment (like maternal infection) has long-standing effects on many organ systems, including the respiratory system. Use of maternal nutritional supplements is an exciting therapeutic option that could be used to protect the developing fetus. In a recent issue of the journal, Ali and associates (Ali M, Heyob KM, Velten M, Tipple TE, Rogers LK. Am J Physiol Lung Cell Mol Physiol 309: L441-L448, 2015) specifically look at maternal docosahexaenoic acid (DHA) supplementation and its effect on chronic apoptosis in the lung in a mouse model of perinatal inflammation and postnatal hyperoxia. Strikingly, the authors show that pulmonary apoptosis was augmented even 8 wk after the hyperoxia-exposed mice had been returned to room air. This effect was significantly attenuated in mice that were subjected to maternal dietary DHA supplementation. These findings are novel, significantly advance our understanding of chronic effects of adverse perinatal and neonatal events on the developing lung, and thereby offer novel therapeutic options in the form of maternal dietary supplementation with DHA. This editorial reviews the long-term effects of adverse perinatal environment on postnatal lung development and the protective effects of dietary supplements such as DHA. Copyright © 2015 the American Physiological Society.

  19. Effectiveness of knowledge translation tools addressing multiple high-burden chronic diseases affecting older adults: protocol for a systematic review alongside a realist review

    PubMed Central

    Kastner, Monika; Perrier, Laure; Hamid, Jemila; Tricco, Andrea C; Cardoso, Roberta; Ivers, Noah M; Liu, Barbara; Marr, Sharon; Holroyd-Leduc, Jayna; Wong, Geoff; Graves, Lisa; Straus, Sharon E

    2015-01-01

    Introduction The burden of chronic disease is a global phenomenon, particularly among people aged 65 years and older. More than half of older adults have more than one chronic disease and their care is not optimal. Chronic disease management (CDM) tools have the potential to meet this challenge but they are primarily focused on a single disease, which fails to address the growing number of seniors with multiple chronic conditions. Methods and analysis We will conduct a systematic review alongside a realist review to identify effective CDM tools that integrate one or more high-burden chronic diseases affecting older adults and to better understand for whom, under what circumstances, how and why they produce their outcomes. We will search MEDLINE, EMBASE, CINAHL, AgeLine and the Cochrane Library for experimental, quasi-experimental, observational and qualitative studies in any language investigating CDM tools that facilitate optimal disease management in one or more high-burden chronic diseases affecting adults aged ≥65 years. Study selection will involve calibration of reviewers to ensure reliability of screening and duplicate assessment of articles. Data abstraction and risk of bias assessment will also be performed independently. Analysis will include descriptive summaries of study and appraisal characteristics, effectiveness of each CDM tool (meta-analysis if appropriate); and a realist programme theory will be developed and refined to explain the outcome patterns within the included studies. Ethics and dissemination Ethics approval is not required for this study. We anticipate that our findings, pertaining to gaps in care across high-burden chronic diseases affecting seniors and highlighting specific areas that may require more research, will be of interest to a wide range of knowledge users and stakeholders. We will publish and present our findings widely, and also plan more active dissemination strategies such as workshops with our key stakeholders. Trial registration number Our protocol is registered with PROSPERO (registration number CRD42014014489). PMID:25649215

  20. Elucidation of innovative antibiofilm materials.

    PubMed

    Marcano, Aracelys; Ba, Ousmane; Thebault, Pascal; Crétois, Raphaël; Marais, Stéphane; Duncan, Anthony C

    2015-12-01

    It is known for roughly a decade that bacterial communities (called biofilms) are responsible for significant enhanced antibiotherapy resistance. Biofilms are involved in tissue persistent infection, causing direct or collateral damage leading to chronic wounds development and impairing natural wound healing. In this study, we are interested in the development of supported protein materials which consist of asymmetric membranes as reservoir supports for the incorporation and controlled release of biomolecules capable of dissolving biofilms (or preventing their formation) and their use as wound dressing for chronic wound treatment. In a first step, polyhydroxyalkanoates (PHAs) asymmetric membranes were prepared using wet phase inversion technique. Scanning microscopy (SEM) analysis has showed the influence of different processing parameters. In a second step, the porous side of the membranes were functionalized with a surface treatment and then loaded with the antibiofilm agent (dispersin B). In a third step, the properties and antibiofilm performance of the loaded-membranes were evaluated. Exposure of Staphylococcus epidermidis biofilms to such systems weakly inhibited biofilm formation (weak preventive effect) but caused their detachment and disaggregation (strong curative effect). These initial results are promising since they open the way to a new generation of effective tools in the struggle against persistent bacterial infections exhibiting enhanced antibiotherapy resistance, and in particular in the case of infected chronic wounds. Copyright © 2015. Published by Elsevier B.V.

  1. Chronic Stress in Adolescents and Its Neurobiological and Psychopathological Consequences: An RDoC Perspective.

    PubMed

    Sheth, Chandni; McGlade, Erin; Yurgelun-Todd, Deborah

    2017-01-01

    The Research Domain Criteria (RDoC) initiative provides a strategy for classifying psychopathology based on behavioral dimensions and neurobiological measures. Neurodevelopment is an orthogonal dimension in the current RDoC framework; however, it has not yet been fully incorporated into the RDoC approach. A combination of both a neurodevelopmental and RDoC approach offers a multidimensional perspective for understanding the emergence of psychopathology during development. Environmental influence (e.g., stress) has a profound impact on the risk for development of psychiatric illnesses. It has been shown that chronic stress interacts with the developing brain, producing significant changes in neural circuits that eventually increase the susceptibility for development of psychiatric disorders. This review highlights effects of chronic stress on the adolescent brain, as adolescence is a period characterized by a combination of significant brain alterations, high levels of stress, and emergence of psychopathology. The literature synthesized in this review suggests that chronic stress-induced changes in neurobiology and behavioral constructs underlie the shared vulnerability across a number of disorders in adolescence. The review particularly focuses on depression and substance use disorders; however, a similar argument can also be made for other psychopathologies, including anxiety disorders. The summarized findings underscore the need for a framework to integrate neurobiological findings from disparate psychiatric disorders and to target transdiagnostic mechanisms across disorders.

  2. Stage 1 development of a patient-reported experience measure (PREM) for chronic obstructive pulmonary disease (COPD).

    PubMed

    Walker, Susan; Andrew, Sharon; Hodson, Matthew; Roberts, C Michael

    2017-07-24

    The study aimed to explore patients' experience of living with chronic obstructive pulmonary disease and their perspective of their community healthcare for chronic obstructive pulmonary disease to extract affective responses in order to develop potential items for a patient-reported experience measure for chronic obstructive pulmonary disease. Qualitative face-face interviews were conducted, in the community, with 64 patients with chronic obstructive pulmonary disease recruited from General Practices and Breathe-Easy community groups in the Outer North East, East and City areas of London and Essex, UK. A two phase analysis of the qualitative data was conducted to identify themes arising from patients' description of living with chronic obstructive pulmonary disease and their perceptions of their community healthcare and subsequently the affective responses underlying the themes raised by patients, which gave emotional colour to the themes, bringing the thematic analysis closer to the subjective patient experience. Five themes were identified from the interview data: 'Journey to diagnosis'; 'Smoking'; 'Usual care'; 'My everyday life'; and 'Exacerbations'. Twenty-one affective responses were identified and categorised as either 'negative', 'positive' or 'bivalent'. 'Frustration', a negative affective response was prevalent in four themes. 'Gratitude', 'hope' and 'happiness/enjoyment' were among the more positive responses more prevalent across several themes. By conducting a novel two-way analysis (thematic and affective) it was possible to identify themes and affective responses that were aligned to those themes. This enabled the development of 38 chronic obstructive pulmonary disease-specific experience items to take forward for further testing including item reduction and validity and reliability in the next stage of the patient-reported experience measure development. GIVING IMPORTANCE TO PATIENTS' EMOTIONS: An exploration of patient perceptions of living with chronic lung disease will help develop a new patient reported experience scale. Healthcare services are aiming to provide effective patient-centered care for those with chronic obstructive pulmonary disease (COPD). Such care strategies require structured, validated patient feedback scales to facilitate accurate communication between patients, carers and healthcare professionals. Susan Walker at Anglia Ruskin University in Chelmsford, UK, and co-workers analyzed qualitative data from interviews with 64 COPD patients in London and Essex regarding their emotions and perceptions of living with COPD, with the aim of creating a patient reported experience measure, or PREM. Initial results identified five themes-including 'journey to diagnosis' and 'everyday life'-and twenty-one affective responses, ranging from negative to positive. The team will take these results forward for further validation.

  3. Chronic airflow limitation in developing countries: burden and priorities

    PubMed Central

    Aït-Khaled, Nadia; Enarson, Donald A; Ottmani, Salah; Sony, Asma El; Eltigani, Mai; Sepulveda, Ricardo

    2007-01-01

    Respiratory disease has never received priority in relation to its impact on health. Estimated DALYs lost in 2002 were 12% globally (similar for industrialized and developing countries). Chronic airflow limitation (due mainly to asthma and COPD) alone affects more than 100 million persons in the world and the majority of them live in developing countries. International guidelines for management of asthma (GINA) and COPD (GOLD) have been adopted and their cost-effectiveness demonstrated in industrialized countries. As resources are scarce in developing countries, adaptation of these guidelines using only essential drugs is required. It remains for governments to set priorities. To make these choices, a set of criteria have been proposed. It is vital that the results of scientific investigations are presented in these terms to facilitate their use by decision-makers. To respond to this emerging public health problem in developing countries, WHO has developed 2 initiatives: “Practical Approach to Lung Health (PAL)” and the Global Alliance Against Chronic Respiratory Diseases (GARD)”, and the International Union Against Tuberculosis and Lung Diseases (The Union) has launched a new initiative to increase affordability of essential asthma drugs for patients in developing countries termed the “Asthma Drug Facility” (ADF), which could facilitate the care of patients living in these parts of the world. PMID:18044686

  4. Chronic airflow limitation in developing countries: burden and priorities.

    PubMed

    Aït-Khaled, Nadia; Enarson, Donald A; Ottmani, Salah; El Sony, Asma; Eltigani, Mai; Sepulveda, Ricardo

    2007-01-01

    Respiratory disease has never received priority in relation to its impact on health. Estimated DALYs lost in 2002 were 12% globally (similar for industrialized and developing countries). Chronic airflow limitation (due mainly to asthma and COPD) alone affects more than 100 million persons in the world and the majority of them live in developing countries. International guidelines for management of asthma (GINA) and COPD (GOLD) have been adopted and their cost-effectiveness demonstrated in industrialized countries. As resources are scarce in developing countries, adaptation of these guidelines using only essential drugs is required. It remains for governments to set priorities. To make these choices, a set of criteria have been proposed. It is vital that the results of scientific investigations are presented in these terms to facilitate their use by decision-makers. To respond to this emerging public health problem in developing countries, WHO has developed 2 initiatives: "Practical Approach to Lung Health (PAL)" and the Global Alliance Against Chronic Respiratory Diseases (GARD)", and the International Union Against Tuberculosis and Lung Diseases (The Union) has launched a new initiative to increase affordability of essential asthma drugs for patients in developing countries termed the "Asthma Drug Facility" (ADF), which could facilitate the care of patients living in these parts of the world.

  5. Air pollution and chronic airway diseases: what should people know and do?

    PubMed

    Jiang, Xu-Qin; Mei, Xiao-Dong; Feng, Di

    2016-01-01

    The health effects of air pollution remain a public health concern worldwide. Exposure to air pollution has many substantial adverse effects on human health. Globally, seven million deaths were attributable to the joint effects of household and ambient air pollution. Subjects with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are especially vulnerable to the detrimental effects of air pollutants. Air pollution can induce the acute exacerbation of COPD and onset of asthma, increase the respiratory morbidity and mortality. The health effects of air pollution depend on the components and sources of pollutants, which varied with countries, seasons, and times. Combustion of solid fuels is a major source of air pollutants in developing countries. To reduce the detrimental effects of air pollution, people especially those with COPD or asthma should be aware of the air quality and take extra measures such as reducing the time outdoor and wearing masks when necessary. For reducing the air pollutants indoor, people should use clean fuels and improve the stoves so as to burn fuel more efficiently and vent emissions to the outside. Air cleaners that can improve the air quality efficiently are recommended.

  6. Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis.

    PubMed

    Okumura, Takako; Murata, Yoko; Taniguchi, Kana; Murase, Akio; Nii, Aisuke

    2008-06-01

    Prostaglandin E2 (PGE2) produced by cyclooxygenase (COX) is a potent pro-inflammatory mediator. We have recently discovered CJ-023,423, a highly selective antagonist of EP4 receptors, one of the PGE2 receptors. This agent is suitable for exploring the effects of blocking EP4 receptors following oral administration in rats. In this study, CJ-023,423 was used in rats with adjuvant-induced arthritis (AIA) to investigate the role of the EP4 receptor in chronic inflammation and bone destruction. These effects were compared with those of rofecoxib, a selective COX-2 inhibitor. CJ-023,423 had significant inhibitory effects on paw swelling, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats. In particular, the inhibitory effect on paw swelling in AIA rats was comparable to that of rofecoxib. These results suggest that PGE2 acting via the EP4 receptor is involved in the development of chronic inflammation and bone destruction, particularly with respect to oedema in AIA rats. This is the first study to confirm the in-vivo effects of EP4 receptor blockade on inflammation and bone destruction in AIA rats with a small-molecule compound.

  7. Air pollution and chronic airway diseases: what should people know and do?

    PubMed Central

    Jiang, Xu-Qin; Feng, Di

    2016-01-01

    The health effects of air pollution remain a public health concern worldwide. Exposure to air pollution has many substantial adverse effects on human health. Globally, seven million deaths were attributable to the joint effects of household and ambient air pollution. Subjects with chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are especially vulnerable to the detrimental effects of air pollutants. Air pollution can induce the acute exacerbation of COPD and onset of asthma, increase the respiratory morbidity and mortality. The health effects of air pollution depend on the components and sources of pollutants, which varied with countries, seasons, and times. Combustion of solid fuels is a major source of air pollutants in developing countries. To reduce the detrimental effects of air pollution, people especially those with COPD or asthma should be aware of the air quality and take extra measures such as reducing the time outdoor and wearing masks when necessary. For reducing the air pollutants indoor, people should use clean fuels and improve the stoves so as to burn fuel more efficiently and vent emissions to the outside. Air cleaners that can improve the air quality efficiently are recommended. PMID:26904251

  8. The effects of assertiveness training in patients with schizophrenia: a randomized, single-blind, controlled study.

    PubMed

    Lee, Tso-Ying; Chang, Shih-Chin; Chu, Hsin; Yang, Chyn-Yng; Ou, Keng-Liang; Chung, Min-Huey; Chou, Kuei-Ru

    2013-11-01

    In this study, we investigated the effects of group assertiveness training on assertiveness, social anxiety and satisfaction with interpersonal communication among patients with chronic schizophrenia. Only limited studies highlighted the effectiveness of group assertiveness training among inpatients with schizophrenia. Given the lack of group assertiveness training among patients with schizophrenia, further development of programmes focusing on facilitating assertiveness, self-confidence and social skills among inpatients with chronic schizophrenia is needed. This study used a prospective, randomized, single-blinded, parallel-group design. This study employed a prospective, randomized, parallel-group design. Seventy-four patients were randomly assigned to experimental group receiving 12 sessions of assertiveness training, or a supportive control group. Data collection took place for the period of June 2009-July 2010. Among patients with chronic schizophrenia, assertiveness, levels of social anxiety and satisfaction with interpersonal communication significantly improved immediately after the intervention and at the 3-month follow-up in the intervention group. The results of a generalized estimating equation (GEE) indicated that: (1) assertiveness significantly improved from pre- to postintervention and was maintained until the follow-up; (2) anxiety regarding social interactions significantly decreased after assertiveness training; and (3) satisfaction with interpersonal communication slightly improved after the 12-session intervention and at the 3-month follow-up. Assertivenss training is a non-invasive and inexpensive therapy that appears to improve assertiveness, social anxiety and interpersonal communication among inpatients with chronic schizophrenia. These findings may provide a reference guide to clinical nurses for developing assertiveness-training protocols. © 2013 Blackwell Publishing Ltd.

  9. Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia.

    PubMed

    De Schutter, Tineke M; Behets, Geert J; Geryl, Hilde; Peter, Mirjam E; Steppan, Sonja; Gundlach, Kristina; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Neven, Ellen

    2013-06-01

    Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification.

  10. Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia

    PubMed Central

    De Schutter, Tineke M; Behets, Geert J; Geryl, Hilde; Peter, Mirjam E; Steppan, Sonja; Gundlach, Kristina; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Neven, Ellen

    2013-01-01

    Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification. PMID:23486515

  11. Canadian guideline for safe and effective use of opioids for chronic noncancer pain

    PubMed Central

    Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

    2011-01-01

    Abstract Objective To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. Quality of evidence Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. Main message Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. Conclusion Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety. PMID:22084455

  12. Canadian guideline for safe and effective use of opioids for chronic noncancer pain: clinical summary for family physicians. Part 1: general population.

    PubMed

    Kahan, Meldon; Mailis-Gagnon, Angela; Wilson, Lynn; Srivastava, Anita

    2011-11-01

    To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain, developed by the National Opioid Use Guideline Group. Researchers for the guideline conducted a systematic review of the literature on the effectiveness and safety of opioids for chronic noncancer pain, and drafted a series of recommendations. A panel of 49 clinicians from across Canada reviewed the draft and achieved consensus on 24 recommendations. Screening for addiction risk is recommended before prescribing opioids. Weak opioids (codeine and tramadol) are recommended for mild to moderate pain that has not responded to first-line treatments. Oxycodone, hydromorphone, and morphine can be tried in patients who have not responded to weaker opioids. A low initial dose and slow upward titration is recommended, with patient education and close monitoring. Physicians should watch for the development of complications such as sleep apnea. The optimal dose is one which improves function or decreases pain ratings by at least 30%. For by far most patients, the optimal dose will be well below a 200-mg morphine equivalent dose per day. Tapering is recommended for patients who have not responded to an adequate opioid trial. Opioids play an important role in the management of chronic noncancer pain, but careful prescribing is needed to limit potential harms. The new Canadian guideline provides much-needed guidance to help physicians achieve a balance between optimal pain control and safety.

  13. The Effectiveness of Mindfulness-Based Stress Reduction on Perceived Pain Intensity and Quality of Life in Patients With Chronic Headache.

    PubMed

    Bakhshani, Nour Mohammad; Amirani, Ahmadreza; Amirifard, Hamed; Shahrakipoor, Mahnaz

    2015-08-06

    The aim of this study was to determine the effectiveness of Mindfulness-Based Stress reduction (MBSR) on perceived pain intensity and quality of life in patients with chronic headache. Thus, forty patients based on the diagnosis of a neurologist and diagnostic criteria of the International Headache Society (IHS) for migraine and chronic tension-type headache were selected and randomly assigned to the intervention group and control group, respectively. The participants completed the Pain and quality of life (SF-36) questionnaire. The intervention group enrolled in an eight-week MBSR program that incorporated meditation and daily home practice, per week, session of 90-minutes. Results of covariance analysis with the elimination of the pre-test showed significantly improvement of pain and quality of life in the intervention group compared with the control group. The findings from this study revealed that MBSR can be used non-pharmacological intervention for improvement the quality of life and development of strategies to cope with pain in patients with chronic headache. And can be used in combination with other therapies such as pharmacotherapy.

  14. Drug delivery systems and materials for wound healing applications.

    PubMed

    Saghazadeh, Saghi; Rinoldi, Chiara; Schot, Maik; Kashaf, Sara Saheb; Sharifi, Fatemeh; Jalilian, Elmira; Nuutila, Kristo; Giatsidis, Giorgio; Mostafalu, Pooria; Derakhshandeh, Hossein; Yue, Kan; Swieszkowski, Wojciech; Memic, Adnan; Tamayol, Ali; Khademhosseini, Ali

    2018-04-05

    Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Role of the inflammasome in chronic obstructive pulmonary disease (COPD).

    PubMed

    Colarusso, Chiara; Terlizzi, Michela; Molino, Antonio; Pinto, Aldo; Sorrentino, Rosalinda

    2017-10-10

    Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), a pulmonary disorder characterized by chronic bronchitis, chronic airway obstruction, emphysema, associated to progressive and irreversible decline of lung function. Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. So far, scientific evidence has focused on nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome, a specialized inflammatory signaling platform that governs the maturation and secretion of IL-1-like cytokines through the regulation of caspase-1-dependent proteolytic processing. Some studies revealed that it is involved during airway inflammation typical of COPD. Based on the influence of cigarette smoke in various respiratory diseases, including COPD, in this view we report its effects in inflammatory and immune responses in COPD mouse models and in human subjects affected by COPD. In sharp contrast to what reported on experimental and clinical studies, randomized clinical trials show that indirect inflammasome inhibitors did not have any beneficial effect in moderate to severe COPD patients.

  16. [Latex ligation in treatment of chronic hemorrhoids].

    PubMed

    Ektov, V N; Somov, K A

    2015-01-01

    We analyzed the results of treatment of 432 patients with chronic hemorrhoids using different variants of latex ligation. New technique including ligation of mucosa and submucosa of low-ampullar rectum providing ligation of hemorrhoidalvessels, lifting and recto-anal repair is developed and suggested. This method is advisable to use in case of chronic internal hemorrhoids stages I and II. The authors recommend simultaneous combined ligation of mucosa of low-ampullar rectum and internal hemorrhoids for stages III and IV. Different variants of latex ligation with external hemorrhoids excision were used in 103 patients. Pointed variants of latex ligation preserve important advantages including mini-invasiveness, simplicity and wide availability, low cost. Good remote results were obtained after these procedures in 87.3% of observations. Suggested tactics extends use of latex ligation and increases its effectiveness in treatment of different stages and forms of chronic hemorrhoids.

  17. [THE ROLE OF SYSTEM QUORUM SENSING UNDER CHRONIC UROGENITAL CHLAMYDIA INFECTION].

    PubMed

    2015-10-01

    It is established that system quorum sensing (QS) assure social behavior of bacteria in regulation of genes of virulence and generalization of inflectional inflammatory process under chronic urogenital chlamydia infection. The techniques of gas chromatography and mass-spectrometry were applied to detect molecular markers of generalization of infectious process under urogenital chlamydiasis--activators of QS microbes (lactones, quinolones, furan ethers). The developed diagnostic gas chromatography and mass-spectrometry criteria of indexation of molecular markers under chronic urogenital chlamydia infection have high level of diagnostic sensitivity, specificity and prognostic value of positive and negative result. The application of techniques of gas chromatography and mass-spectrometry permits enhancing effectiveness of diagnostic of chronic inflectional inflammatory diseases of urogenital system of chlamydia etiology with identification of prognostic criteria of generalization of infectious process and subsequent prescription of timely and appropriate therapy

  18. Development of a conceptual framework for understanding financial barriers to care among patients with cardiovascular-related chronic disease: a protocol for a qualitative (grounded theory) study.

    PubMed

    Campbell, David J T; Manns, Braden J; Hemmelgarn, Brenda R; Sanmartin, Claudia; King-Shier, Kathryn M

    2016-01-01

    Patients with cardiovascular-related chronic diseases may face financial barriers to accessing health care, even in Canada, where universal health care insurance is in place. No current theory or framework is adequate for understanding the impact of financial barriers to care on these patients or how they experience financial barriers. The overall objective of this study is to develop a framework for understanding the role of financial barriers to care in the lives of patients with cardiovascular-related chronic diseases and the impact of such barriers on their health. We will perform an inductive qualitative grounded theory study to develop a framework to understand the effect of financial barriers to care on patients with cardiovascular-related chronic diseases. We will use semistructured interviews (face-to-face and telephone) with a purposive sample of adult patients from Alberta with at least 1 of hypertension, diabetes, heart disease or stroke. We will analyze interview transcripts in triplicate using grounded theory coding techniques, including open, focused and axial coding, following the principle of constant comparison. Interviews and analysis will be done iteratively to theoretical saturation. Member checking will be used to enhance rigour. A comprehensive framework for understanding financial barriers to accessing health care is instrumental for both researchers and clinicians who care for patients with chronic diseases. Such a framework would enable a better understanding of patient behaviour and nonadherence to recommended medical therapies and lifestyle modifications.

  19. Monoamine Transporter Inhibitors and Substrates as Treatments for Stimulant Abuse

    PubMed Central

    Howell, Leonard L.; Negus, S. Stevens

    2015-01-01

    The acute and chronic effects of abused psychostimulants on monoamine transporters and associated neurobiology have encouraged development of candidate medications that target these transporters. Monoamine transporters in general, and dopamine transporters in particular, are critical molecular targets that mediate abuse-related effects of psychostimulants such as cocaine and amphetamine. Moreover, chronic administration of psychostimulants can cause enduring changes in neurobiology reflected in dysregulation of monoamine neurochemistry and behavior. The current review will evaluate evidence for the efficacy of monoamine transporter inhibitors and substrates to reduce abuse-related effects of stimulants in preclinical assays of stimulant self-administration, drug discrimination and reinstatement. In considering deployment of monoamine transport inhibitors and substrates as agonist-type medications to treat stimulant abuse, the safety and abuse liability of the medications are an obvious concern, and this will also be addressed. Future directions in drug discovery should identify novel medications that retain efficacy to decrease stimulant use but possess lower abuse liability, and evaluate the degree to which efficacious medications can attenuate or reverse neurobiological effects of chronic stimulant use. PMID:24484977

  20. Sodium channel γENaC mediates IL-17 synergized high salt induced inflammatory stress in breast cancer cells

    PubMed Central

    Amara, Suneetha; Ivy, Michael T; Myles, Elbert L; Tiriveedhi, Venkataswarup

    2015-01-01

    Chronic inflammation is known to play a critical role in the development of cancer. Recent evidence suggests that high salt in the tissue microenvironment induces chronic inflammatory milieu. In this report, using three breast cancer-related cell lines, we determined the molecular basis of the potential synergistic inflammatory effect of sodium chloride (NaCl) with interleukin-17 (IL-17). Combined treatment of high NaCl (0.15 M) with sub-effective IL-17 (0.1 nM) induced enhanced growth in breast cancer cells along with activation of reactive nitrogen and oxygen (RNS/ROS) species known to promote cancer. Similar effect was not observed with equi-molar mannitol. This enhanced of ROS/RNS activity correlates with upregulation of γENaC an inflammatiory sodium channel. The similar culture conditions have also induced expression of pro-inflammatory cytokines such as IL-6, TNFα etc. Taken together, these data suggest that high NaCl in the cellular microenvironment induces a γENaC mediated chronic inflammatory response with a potential pro-carcinogenic effect. PMID:26723502

  1. The evolution of the surgical treatment of chronic pancreatitis.

    PubMed

    Andersen, Dana K; Frey, Charles F

    2010-01-01

    To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis.

  2. Therapeutic Role of Functional Components in Alliums for Preventive Chronic Disease in Human Being

    PubMed Central

    Li, Yuping; Yang, Jiazhen; Pu, Xiaoying; Du, Juan; Yang, Xiaomeng; Yang, Tao; Yang, Shuming

    2017-01-01

    Objectives. Functional components in alliums have long been maintained to play a key role in modifying the major risk factors for chronic disease. To obtain a better understanding of alliums for chronic disease prevention, we conducted a systematic review for risk factors and prevention strategies for chronic disease of functional components in alliums, based on a comprehensive English literature search that was conducted using various electronic search databases, especially the PubMed, ISI Web of Science, and CNKI for the period 2007–2016. Allium genus especially garlic, onion, and Chinese chive is rich in organosulfur compounds, quercetin, flavonoids, saponins, and others, which have anticancer, preventive cardiovascular and heart diseases, anti-inflammation, antiobesity, antidiabetes, antioxidants, antimicrobial activity, neuroprotective and immunological effects, and so on. These results support Allium genus; garlic and onion especially may be the promising dietotherapeutic vegetables and organopolysulfides as well as quercetin mechanism in the treatment of chronic diseases. This review may be used as scientific basis for the development of functional food, nutraceuticals, and alternative drugs to improve the chronic diseases. PMID:28261311

  3. CHRONIOUS: a wearable platform for monitoring and management of patients with chronic disease.

    PubMed

    Bellos, Christos; Papadopoulos, Athanassios; Rosso, Roberto; Fotiadis, Dimitrios I

    2011-01-01

    The CHRONIOUS system has been developed based on an open architecture design that consists of a set of subsystems which interact in order to provide all the needed services to the chronic disease patients. An advanced multi-parametric expert system is being implemented that fuses information effectively from various sources using intelligent techniques. Data are collected by sensors of a body network controlling vital signals while additional tools record dietary habits and plans, drug intake, environmental and biochemical parameters and activity data. The CHRONIOUS platform provides guidelines and standards for the future generations of "chronic disease management systems" and facilitates sophisticated monitoring tools. In addition, an ontological information retrieval system is being delivered satisfying the necessities for up-to-date clinical information of Chronic Obstructive pulmonary disease (COPD) and Chronic Kidney Disease (CKD). Moreover, support tools are being embedded in the system, such as the Mental Tools for the monitoring of patient mental health status. The integrated platform provides real-time patient monitoring and supervision, both indoors and outdoors and represents a generic platform for the management of various chronic diseases.

  4. The effects of obesity on doctor-diagnosed chronic diseases in Africa: empirical results from Senegal and South Africa.

    PubMed

    Asfaw, Abay

    2006-01-01

    While inadequate food and communicable infectious diseases have been a concern of researchers and policy makers in Africa, little attention has been given to obesity and chronic, non-communicable diseases. Africa is not usually associated with obesity and chronic diseases. Yet there has been a sharp rise in the incidence of obesity and chronic diseases, a major public health problem in many countries. The paper examines the impact of obesity on the prevalence of four doctor-diagnosed chronic diseases in Senegal and South Africa. The results reveal that obese respondents were 4.7, 2.8, and 4.8% more likely to face the risks of arthritis, diabetes, and heart diseases in South Africa and 6.5 and 7.4% more likely to face the risks of heart disease and asthma in Senegal than their lean counterparts. Obesity imposes a real and substantial danger, affecting the prevalence of chronic diseases. Unchecked it can be a major public health problem, impose a serious challenge to the health sector, and can jeopardize future developments.

  5. Time dependent effect of chronic embryonic exposure to ethanol on zebrafish: Morphology, biochemical and anxiety alterations.

    PubMed

    Ramlan, Nurul Farhana; Sata, Nurul Syafida Asma Mohd; Hassan, Siti Norhidayah; Bakar, Noraini Abu; Ahmad, Syahida; Zulkifli, Syaizwan Zahmir; Abdullah, Che Azurahanim Che; Ibrahim, Wan Norhamidah Wan

    2017-08-14

    Exposure to ethanol during critical period of development can cause severe impairments in the central nervous system (CNS). This study was conducted to assess the neurotoxic effects of chronic embryonic exposure to ethanol in the zebrafish, taking into consideration the time dependent effect. Two types of exposure regimen were applied in this study. Withdrawal exposure group received daily exposure starting from gastrulation until hatching, while continuous exposure group received daily exposure from gastrulation until behavioural assessment at 6dpf (days post fertilization). Chronic embryonic exposure to ethanol decreased spontaneous tail coiling at 24hpf (hour post fertilization), heart rate at 48hpf and increased mortality rate at 72hpf. The number of apoptotic cells in the embryos treated with ethanol was significantly increased as compared to the control. We also measured the morphological abnormalities and the most prominent effects can be observed in the treated embryos exposed to 1.50% and 2.00%. The treated embryos showed shorter body length, larger egg yolk, smaller eye diameter and heart edema as compared to the control. Larvae received 0.75% continuous ethanol exposure exhibited decreased swimming activity and increased anxiety related behavior, while withdrawal ethanol exposure showed increased swimming activity and decreased anxiety related behavior as compared to the respective control. Biochemical analysis exhibited that ethanol exposure for both exposure regimens altered proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. Our results indicated that time dependent effect of ethanol exposure during development could target the biochemical processes thus leading to induction of apoptosis and neurobehavioral deficits in the zebrafish larvae. Thus it raised our concern about the safe limit of alcohol consumption for pregnant mother especially during critical periods of vulnerability for developing nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Chronic disease management and the home-care alternative in Ontario, Canada.

    PubMed

    Tsasis, Peter

    2009-08-01

    The pressure on our health-care system to deliver efficient, quality and cost-effective care is increasing. The debate on its sustainability is also expanding. These challenges can be managed with revisions to our health-care policy frameworks governing how and what public health-care services are delivered. Chronic disease management and home care can together ease many of the present and future pressures facing the health-care system. However, the current level of investment and the present policy are not effectively supporting movement in this direction. Updating the Canada Health Act to reflect the realities of our health-care system, and developing policies to support the areas of interdisciplinary teamwork and system integration are needed to facilitate chronic disease management and home care in Canada. This article lays out the challenges, highlights the impending issues and suggests a framework for moving forward.

  7. Asthma Management in the Era of Smart-Medicine: Devices, Gadgets, Apps and Telemedicine.

    PubMed

    Katwa, Umakanth; Rivera, Estefania

    2018-03-10

    Asthma is the most common chronic pediatric condition. Effective asthma management requires a proactive and inclusive approach that controls the patient's symptoms and prevents recurrence of exacerbations. Clinicians should encourage patients to become involved in their management since self-management approaches have proven to be an effective means for chronic illness treatment. Novel forms of self-monitoring and management are technological interventions. In the last decade, novel technology has been developed and used to improve asthma control since it is a powerful agent that addresses a variety of challenges in chronic disease management such as education, communication and adherence. A myriad of technology-based strategies are available although many of these are not evidence based and further studies are needed to evaluate their efficacy in specific asthma-control endpoints. Herein, authors present a review of current and future technology-based options for asthma management and a comparison between them.

  8. Chronic Viral Hepatitis in Malaysia: "Where are we now?"

    PubMed

    Raihan, Ruksana; Mohamed, Rosmawati; Radzi Abu Hassan, Muhammad; Md Said, Rosaida

    2017-01-01

    Malaysia is a country where an estimated 1 million people are chronically infected with hepatitis B virus (HBV) and an estimated 2.5% of the adult population are positive for antibody to hepatitis C virus (HCV). Effective nationwide vaccine coverage seems to be a highly effective measure to prevent new HBV infection. Treatment of HCV infection is also a regular practice in Malaysia. These measures highlight the possibility to reach the World Health Organization elimination target by 2030. To achieve this target, the Health Ministry and other nongovernmental organizations, such as My Commitment to Cure (MyC2C) are working together to develop a strategic road map to reach the global elimination target in Malaysia by 2030. How to cite this article: Raihan R, Mohamed R, Hasan MRA, Rosaida MS. Chronic Viral Hepatitis in Malaysia: "Where are we now?" Euroasian J Hepato-Gastroenterol 2017;7(1):65-67.

  9. Long-term ingestion of cassava (tapioca) does not produce diabetes or pancreatitis in the rat model.

    PubMed

    Mathangi, D C; Deepa, R; Mohan, V; Govindarajan, M; Namasivayam, A

    2000-06-01

    Cassava (tapioca, manihot) is consumed as a staple food in some developing countries. The intake of cassava has been linked to several diseases including fibrocalculous pancreatic diabetes (tropical calcific pancreatitis). There are few long-term studies on the effect of cassava ingestion on the pancreas in animal models. This article reports on the long-term (up to 1 yr) effects of cassava in the rat model. We found that cassava did not produce diabetes in the rat even after a year of cassava feeding. There were transient changes in serum insulin and lipase levels, but the significance of these findings are not clear. There was no histopathological evidence of either acute or chronic pancreatitis, but there were changes of toxic hepatitis in the liver. In conclusion, chronic cassava ingestion up to a year does not lead to either diabetes or chronic pancreatitis in the rat model.

  10. Traumatic brain injury: a risk factor for neurodegenerative diseases.

    PubMed

    Gupta, Rajaneesh; Sen, Nilkantha

    2016-01-01

    Traumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages.

  11. Effects of a sustained-release naloxone pellet on luteinizing hormone secretion in female rats.

    PubMed

    Gabriel, S M; Simpkins, J W

    1983-11-01

    Studies were undertaken to develop a naloxone implant capable of chronically blocking opioid receptors for several weeks in an effort to evaluate the effect of this prolonged narcotic antagonism on luteinizing hormone (LH) secretion in female rats. Antagonism of opiate receptors was achieved with a tablet formulation which contained 75 mg naloxone free base and a high content of the insoluble binding material, Mg stearate. Subcutaneous placement of this implant prevented morphine-induced analgesia for 2 weeks and antagonized the LH suppressory effects of morphine (15 or 30 mg/kg) administration. Thus, this naloxone delivery system is capable of chronically occupying the opioid receptors which mediate morphine's effects on analgesia and LH secretion. Despite this, the naloxone pellet only moderately enhanced the initial rate of increase in LH secretion following ovariectomy (day 1) and was ineffective in further augmenting LH secretion at 3 and 7 days after implantation. In rats which were ovariectomized and implanted immediately with estradiol-containing Silastic capsules, the naloxone pellet was ineffective in altering LH secretion 1, 3 or 7 days later. Thus, while chronic exposure to naloxone persistently antagonizes the pharmacologic actions of morphine, the naloxone pellet only transiently blocked the tonic inhibitory effect of endogenous opioid peptides. The mechanism by which the LH secretory effects of naloxone are lost following chronic exposure to the antagonist are at present unknown, but may involve the activation of compensatory mechanisms which are inhibitory to LH secretion.

  12. Health, "illth," and economic growth: medicine, environment, and economics at the crossroads.

    PubMed

    Egger, Garry

    2009-07-01

    Economic growth has been the single biggest contributor to population health since the Industrial Revolution. The growth paradigm, by definition, is dynamic, implying similar diminishing returns on investment at both the macro- and the micro-economic levels. Changes in patterns of health in developing countries, from predominantly microbial-related infectious diseases to lifestyle-related chronic diseases (e.g., obesity, type 2 diabetes) beyond a point of economic growth described as the epidemiologic transition, suggest the start of certain declining benefits from further investment in the growth model. These changes are reflected in slowing improvements in some health indices (e.g., mortality, infant mortality) and deterioration in others (e.g., disability-associated life years, obesity, chronic diseases). Adverse environmental consequences, such as climate change from economic development, are also related to disease outcomes through the development of inflammatory processes due to an immune reaction to new environmental and lifestyle-related inducers. Both increases in chronic disease and climate change can be seen as growth problems with a similar economic cause and potential economic and public health-rather than personal health-solutions. Some common approaches for dealing with both are discussed, with a plea for greater involvement by health scientists in the economic and environmental debates in order to deal effectively with issues like obesity and chronic disease.

  13. Self-management programs for Aboriginal and Torres Strait Islander Peoples with chronic conditions: A rapid review.

    PubMed

    Moore, Ellie; Lawn, Sharon; Oster, Candice; Morello, Andrea

    2017-01-01

    Objectives Review the evidence for the effectiveness of chronic condition self-management programs applied to Aboriginal and Torres Strait Islander Peoples. Methods A rapid review methodology was followed to develop an evidence summary from peer-reviewed and grey literature. Results Only seven peer-reviewed studies were identified. The evidence indicated that group programs, particularly the Stanford Program, and structured individual chronic condition self-management programs were of good quality for Aboriginal and Torres Strait Islander Peoples, although these need to be integrated into practice in order to see the greatest benefits. The Flinders Program showed promise as a standardised program with content designed specifically with and for these populations. Numerous grey literature sources were identified, many using strong participatory approaches developed locally within Aboriginal and Torres Strait Islander Peoples. However, few of these programs have been subject to rigorous evaluation. Discussion Despite the significant focus on chronic condition self-management programs to help address the burden of disease for Aboriginal and Torres Strait Islander Peoples, few studies exist that have been properly evaluated. The Closing the Gap Principles developed by the Australian Institute of Health and Welfare offer important guidance for how to proceed to maximise engagement, cultural appropriateness and ownership of program initiatives.

  14. COMPARING THE EFFECTS OF RETINOIC ACID ON AMPHIBIAN LIMB DEVELOPMENT AND LETHALITY: CHRONIC EXPOSURE RESULTS IN LETHALITY NOT LIMB MALFORMATIONS

    EPA Science Inventory

    Recently, high frequencies of malformations have been reported in amphibians across the United States. It has been suggested that the malformations may be the result of xenobiotic disruption of retinoid signaling pathways during embryogenesis and tadpole development. Therefore, a...

  15. Understanding alcohol use disorders with neuroelectrophysiology

    PubMed Central

    RANGASWAMY, MADHAVI; PORJESZ, BERNICE

    2015-01-01

    Neurocognitive deficits associated with impairments in various brain regions and neural circuitries, particularly involving frontal lobes, have been associated with chronic alcoholism, as well as with a predisposition to develop alcohol use and related disorders (AUDs). AUD is a multifactorial disorder caused by complex interactions between behavioral, genetic, and environmental liabilities. Neuroelectrophysiological techniques are instrumental in understanding brain and behavior relationships and have also proved very useful in evaluating the genetic diathesis of alcoholism. This chapter describes findings from neuroelectrophysiological measures (electroencephalogram, event-related potentials, and event-related oscillations) related to acute and chronic effects of alcohol on the brain and those that reflect underlying deficits related to a predisposition to develop AUDs and related disorders. The utility of these measures as effective endophenotypes to identify and understand genes associated with brain electrophysiology, cognitive networks, and AUDs has also been discussed. PMID:25307587

  16. Developing a nurse-led clinic using transformational leadership.

    PubMed

    Gousy, Mamood; Green, Kim

    2015-03-25

    Nurses are at the forefront of implementing and managing change, given constantly changing healthcare services and the increase in demand for health care. Therefore, it is important to identify the best style of leadership to engage nurses in implementing service-led improvements. This article explores the effects of transformational leadership in bringing about service-led improvements in health care, using the example of setting up a nurse-led acupuncture clinic to optimise the care of patients with chronic pain. Transformational leadership was used throughout the project - from the initial local planning, training and development, through to liaising with the appropriate staff and deciding on an evaluation strategy. Transformational leadership proved to be an effective way to engage and empower nurses and other members of the chronic pain team to enable them to achieve the project aims.

  17. Effectiveness of Citrus Fruits on Helicobacter pylori

    PubMed Central

    2017-01-01

    It is known that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects of the treatment regimens and the development of antimicrobial resistance, a number of natural compounds have been tested as potential alternatives. In this review, we will examine the current knowledge on the effect of Citrus fruits and their derivatives against H. pylori, highlighting the remaining outstanding questions on the development of novel therapeutic strategies. PMID:28408943

  18. Association between microRNA polymorphisms and chronic pancreatitis.

    PubMed

    Wang, Zhaozhi; Li, Diangeng; Jin, Jianjun; Wang, Qianshou; Zhao, Shuangqin; Bai, Yanli

    2016-01-01

    MicroRNAs play important roles in the development and progression of many human diseases. mir-146a could significantly suppress the induction of proinflammatory cytokines IL-1β, IL-6, TNF-α, NF-κB and chemokine MCP-1, which might play important roles in chronic pancreatitis. This study was conducted to evaluate the association between mir-146a rs2910164, a functional polymorphism in the pre-mir-146a, and chronic pancreatitis risk. The rs2910164 genotypes were determined in 165 patients with chronic pancreatitis and 200 healthy controls who were frequency matched for age and gender. One single nucleotide polymorphism (rs2910164) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). The frequency of individuals who carried [G] allele was significantly higher in cases (62.7%) than in controls (53.7%, p = 0.015), which resulted in a statistically significant pathogenic effect associated with this variant allele (OR: 1.448, CI: 1.076-1.950; p = 0.015). The GC and GG genotypes showed strong and significant increased risk for complication of chronic pancreatitis (OR = 3.668, 95%CI = 1.233-10.916, p = 0.019; OR = 5.667, 95%CI = 1.852-17.336, p = 0.002). The individuals carrying G allele confer a lower expression level of mature mir-146a. These findings suggest that the mir-146a rs2910164 may contribute to genetic susceptibility to chronic pancreatitis, and that mir-146a might be involved in chronic pancreatitis development. Copyright © 2016. Published by Elsevier India Pvt Ltd.

  19. A Chronic Disease Management Student-Faculty Collaborative Practice: Educating Students on Innovation in Health Care Delivery.

    PubMed

    Remus, Kristin E; Honigberg, Michael; Tummalapalli, Sri Lekha; Cohen, Laura P; Fazio, Sara; Weinstein, Amy R

    2016-07-01

    In the current transformative health care landscape, it is imperative that clinician educators inspire future clinicians to practice primary care in a dynamic environment. A focus on patient-centered, goal-oriented care for patients with chronic conditions is critical. In 2009, Harvard Medical School founded the Crimson Care Collaborative, a student-faculty collaborative practice (SFCP) network. With the aim of expanding clinical and educational opportunities for medical students and improving patient control of chronic disease (i.e., hypertension, obesity, and diabetes) in an innovative learning environment, in 2012, the authors developed a novel SFCP at their hospital-based academic primary care practice. In this SFCP, students learn to explore patient priorities, provide focused counseling and education, and assist patients with self-management goals during clinical visits. From 2012 to 2014, 250 student volunteers participated in the SFCP as clinicians, innovators, educators, and leaders, with between 80 and 95 medical students engaging each semester. Between January 2012 and March 2014, there were 476 urgent care or chronic disease management visits. Patients with chronic diseases were seen at least twice on average, and by 2014, chronic disease management visits accounted for approximately 74% of visits. Work is under way to create assessment tools to evaluate the practice's educa tional impact and student understanding of the current health care system, develop interdisciplinary care teams, expand efforts in registry management and broaden the patient recruitment scope, further emphasize patient engage ment and retention, and evaluate chronic disease management and patient satisfaction effectiveness.

  20. Chronic baclofen desensitizes GABA(B)-mediated G-protein activation and stimulates phosphorylation of kinases in mesocorticolimbic rat brain.

    PubMed

    Keegan, Bradley M T; Beveridge, Thomas J R; Pezor, Jeffrey J; Xiao, Ruoyu; Sexton, Tammy; Childers, Steven R; Howlett, Allyn C

    2015-08-01

    The GABAB receptor is a therapeutic target for CNS and neuropathic disorders; however, few preclinical studies have explored effects of chronic stimulation. This study evaluated acute and chronic baclofen treatments on GABAB-activated G-proteins and signaling protein phosphorylation as indicators of GABAB signaling capacity. Brain sections from rats acutely administered baclofen (5 mg/kg, i.p.) showed no significant differences from controls in GABAB-stimulated GTPγS binding in any brain region, but displayed significantly greater phosphorylation/activation of focal adhesion kinase (pFAK(Tyr397)) in mesocorticolimbic regions (caudate putamen, cortex, hippocampus, thalamus) and elevated phosphorylated/activated glycogen synthase kinase 3-β (pGSK3β(Tyr216)) in the prefrontal cortex, cerebral cortex, caudate putamen, nucleus accumbens, thalamus, septum, and globus pallidus. In rats administered chronic baclofen (5 mg/kg, t.i.d. for five days), GABAB-stimulated GTPγS binding was significantly diminished in the prefrontal cortex, septum, amygdala, and parabrachial nucleus compared to controls. This effect was specific to GABAB receptors: there was no effect of chronic baclofen treatment on adenosine A1-stimulated GTPγS binding in any region. Chronically-treated rats also exhibited increases in pFAK(Tyr397) and pGSK3β(Tyr216) compared to controls, and displayed wide-spread elevations in phosphorylated dopamine- and cAMP-regulated phosphoprotein-32 (pDARPP-32(Thr34)) compared to acutely-treated or control rats. We postulate that those neuroadaptive effects of GABAB stimulation mediated by G-proteins and their sequelae correlate with tolerance to several of baclofen's effects, whereas sustained signaling via kinase cascades points to cross-talk between GABAB receptors and alternative mechanisms that are resistant to desensitization. Both desensitized and sustained signaling pathways should be considered in the development of pharmacotherapies targeting the GABA system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Candida albicans chronic colonisation in cystic fibrosis may be associated with inhaled antibiotics.

    PubMed

    Noni, Maria; Katelari, Anna; Kaditis, Athanasios; Theochari, Ioanna; Lympari, Ioulia; Alexandrou-Athanassoulis, Helen; Doudounakis, Stavros-Eleftherios; Dimopoulos, George

    2015-07-01

    Candida albicans is increasingly recognised as a coloniser of the respiratory tract in cystic fibrosis (CF) patients. Yet, the potential role, if any, of the micro-organism in the progress of the disease remains unclear. In this study, we investigated the association between inhaled antibiotics and C. albicans chronic colonisation in patients with CF. A cohort of 121 CF patients born from 1988 to 1996 was, respectively, studied. The medical records of each patient were reviewed from the first time they attended the CF Centre until the occurrence of C. albicans chronic colonisation or their last visit for the year 2010. Chronic colonisation was defined as the presence of C. albicans in more than 50% of cultures in a given year. A number of possible confounders were included in the multivariate logistic regression analysis to identify an independent association between inhaled antibiotics and C. albicans chronic colonisation. Fifty-four (44.6%) of the 121 patients enrolled in the study developed chronic colonisation by the micro-organism. Multivariate logistic regression analysis determined the independent effect of inhaled antibiotic treatment on the odds of chronic colonisation (OR 1.112, 95% CI [1.007-1.229], P = 0.036). Candida albicans chronic colonisation may be associated with the duration of inhaled antibiotic treatment. © 2015 Blackwell Verlag GmbH.

  2. Chronic stress sensitizes rats to pancreatitis induced by cerulein: Role of TNF-α

    PubMed Central

    Binker, Marcelo G; Binker-Cosen, Andres A; Richards, Daniel; Gaisano, Herbert Y; de Cosen, Rodica H; Cosen-Binker, Laura I

    2010-01-01

    AIM: To investigate chronic stress as a susceptibility factor for developing pancreatitis, as well as tumor necrosis factor-α (TNF-α) as a putative sensitizer. METHODS: Rat pancreatic acini were used to analyze the influence of TNF-α on submaximal (50 pmol/L) cholecystokinin (CCK) stimulation. Chronic restraint (4 h every day for 21 d) was used to evaluate the effects of submaximal (0.2 μg/kg per hour) cerulein stimulation on chronically stressed rats. RESULTS: In vitro exposure of pancreatic acini to TNF-α disorganized the actin cytoskeleton. This was further increased by TNF-α/CCK treatment, which additionally reduced amylase secretion, and increased trypsin and nuclear factor-κB activities in a protein-kinase-C δ and ε-dependent manner. TNF-α/CCK also enhanced caspases’ activity and lactate dehydrogenase release, induced ATP loss, and augmented the ADP/ATP ratio. In vivo, rats under chronic restraint exhibited elevated serum and pancreatic TNF-α levels. Serum, pancreatic, and lung inflammatory parameters, as well as caspases’activity in pancreatic and lung tissue, were substantially enhanced in stressed/cerulein-treated rats, which also experienced tissues’ ATP loss and greater ADP/ATP ratios. Histological examination revealed that stressed/cerulein-treated animals developed abundant pancreatic and lung edema, hemorrhage and leukocyte infiltrate, and pancreatic necrosis. Pancreatitis severity was greatly decreased by treating animals with an anti-TNF-α-antibody, which diminished all inflammatory parameters, histopathological scores, and apoptotic/necrotic markers in stressed/cerulein-treated rats. CONCLUSION: In rats, chronic stress increases susceptibility for developing pancreatitis, which involves TNF-α sensitization of pancreatic acinar cells to undergo injury by physiological cerulein stimulation. PMID:21105189

  3. Prevention and management of chronic disease: a litmus test for health-systems strengthening in low-income and middle-income countries.

    PubMed

    Samb, Badara; Desai, Nina; Nishtar, Sania; Mendis, Shanti; Bekedam, Henk; Wright, Anna; Hsu, Justine; Martiniuk, Alexandra; Celletti, Francesca; Patel, Kiran; Adshead, Fiona; McKee, Martin; Evans, Tim; Alwan, Ala; Etienne, Carissa

    2010-11-20

    National health systems need strengthening if they are to meet the growing challenge of chronic diseases in low-income and middle-income countries. By application of an accepted health-systems framework to the evidence, we report that the factors that limit countries' capacity to implement proven strategies for chronic diseases relate to the way in which health systems are designed and function. Substantial constraints are apparent across each of the six key health-systems components of health financing, governance, health workforce, health information, medical products and technologies, and health-service delivery. These constraints have become more evident as development partners have accelerated efforts to respond to HIV, tuberculosis, malaria, and vaccine-preventable diseases. A new global agenda for health-systems strengthening is arising from the urgent need to scale up and sustain these priority interventions. Most chronic diseases are neglected in this dialogue about health systems, despite the fact that non-communicable diseases (most of which are chronic) will account for 69% of all global deaths by 2030 with 80% of these deaths in low-income and middle-income countries. At the same time, advocates for action against chronic diseases are not paying enough attention to health systems as part of an effective response. Efforts to scale up interventions for management of common chronic diseases in these countries tend to focus on one disease and its causes, and are often fragmented and vertical. Evidence is emerging that chronic disease interventions could contribute to strengthening the capacity of health systems to deliver a comprehensive range of services-provided that such investments are planned to include these broad objectives. Because effective chronic disease programmes are highly dependent on well-functioning national health systems, chronic diseases should be a litmus test for health-systems strengthening. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. The hypothalamic–pituitary–adrenal axis and sex hormones in chronic stress and obesity: pathophysiological and clinical aspects

    PubMed Central

    Pasquali, Renato

    2012-01-01

    Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment. PMID:22612409

  5. Toxoplasma gondii and schizophrenia: a review of published RCTs.

    PubMed

    Chorlton, Sam D

    2017-07-01

    Over the last 60 years, accumulating evidence has suggested that acute, chronic, and maternal Toxoplasma gondii infections predispose to schizophrenia. More recent evidence suggests that chronically infected patients with schizophrenia present with more severe disease. After acute infection, parasites form walled cysts in the brain, leading to lifelong chronic infection and drug resistance to commonly used antiparasitics. Chronic infection is the most studied and closely linked with development and severity of schizophrenia. There are currently four published randomized controlled trials evaluating antiparasitic drugs, specifically azithromycin, trimethoprim, artemisinin, and artemether, in patients with schizophrenia. No trials have demonstrated a change in psychopathology with adjunctive treatment. Published trials have either selected drugs without evidence against chronic infection or used them at doses too low to reduce brain cyst burden. Furthermore, trials have failed to achieve sufficient power or account for confounders such as previous antipsychotic treatment, sex, age, or rhesus status on antiparasitic effect. There are currently no ongoing trials of anti-Toxoplasma therapy in schizophrenia despite ample evidence to justify further testing.

  6. Association of Sleep Duration with Chronic Diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

    PubMed Central

    von Ruesten, Anne; Weikert, Cornelia; Fietze, Ingo; Boeing, Heiner

    2012-01-01

    Background In view of the reduced number of hours devoted to sleep in modern western societies the question arises what effects might result from sleep duration on occurrence of chronic diseases. Methods Data from 23 620 middle-aged participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, that were recruited between 1994–1998, were analyzed by using Cox proportional hazard regression to examine the association between self-reported sleep duration at baseline and incidence of chronic diseases, such as diabetes, myocardial infarction, stroke, and cancer. Results During a mean follow-up period of 7.8 years 841 incident cases of type 2 diabetes, 197 cases of myocardial infarction, 169 incident strokes, and 846 tumor cases were observed. Compared to persons sleeping 7-<8 h/day, participants with sleep duration of <6 h had a significantly increased risk of stroke (Hazard Ratio (HR) = 2.06, 95% confidence interval (CI): 1.18–3.59), cancer (HR = 1.43, 95% CI: 1.09–1.87), and overall chronic diseases (HR = 1.31, 95% CI: 1.10–1.55) in multivariable adjusted models. Self-reported daytime sleep at baseline was not associated with incident chronic diseases in the overall study sample. However, there had been an effect modification of daytime sleep by hypertension showing that daytime sleep was inversely related to chronic disease risk among non-hypertensive participants but directly related to chronic diseases among hypertensives. Conclusion Sleep duration of less than 6 h is a risky behavior for the development of chronic diseases, particularly stroke and cancer, and should be therefore addressed in public health campaigns. PMID:22295122

  7. Association of sleep duration with chronic diseases in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study.

    PubMed

    von Ruesten, Anne; Weikert, Cornelia; Fietze, Ingo; Boeing, Heiner

    2012-01-01

    In view of the reduced number of hours devoted to sleep in modern western societies the question arises what effects might result from sleep duration on occurrence of chronic diseases. Data from 23 620 middle-aged participants of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, that were recruited between 1994-1998, were analyzed by using Cox proportional hazard regression to examine the association between self-reported sleep duration at baseline and incidence of chronic diseases, such as diabetes, myocardial infarction, stroke, and cancer. During a mean follow-up period of 7.8 years 841 incident cases of type 2 diabetes, 197 cases of myocardial infarction, 169 incident strokes, and 846 tumor cases were observed. Compared to persons sleeping 7-<8 h/day, participants with sleep duration of <6 h had a significantly increased risk of stroke (Hazard Ratio (HR) = 2.06, 95% confidence interval (CI): 1.18-3.59), cancer (HR = 1.43, 95% CI: 1.09-1.87), and overall chronic diseases (HR = 1.31, 95% CI: 1.10-1.55) in multivariable adjusted models. Self-reported daytime sleep at baseline was not associated with incident chronic diseases in the overall study sample. However, there had been an effect modification of daytime sleep by hypertension showing that daytime sleep was inversely related to chronic disease risk among non-hypertensive participants but directly related to chronic diseases among hypertensives. Sleep duration of less than 6 h is a risky behavior for the development of chronic diseases, particularly stroke and cancer, and should be therefore addressed in public health campaigns.

  8. [A retrospective study on the incidence of chronic renal failure in the Department of Internal Medicine and Nephrology at University Hospital of Antananarivo (the capital city of Madagascar)].

    PubMed

    Ramilitiana, Benja; Ranivoharisoa, Eliane Mikkelsen; Dodo, Mihary; Razafimandimby, Evanirina; Randriamarotia, Willy Franck

    2016-01-01

    Chronic renal failure is a global public health problem. In developed countries, this disease occurs mainly in the elderly, but in Africa it rather affects active young subjects. This disease need for expensive treatments in a low income country, because of its costs. Our aim is to describe the epidemiology of new cases of chronic renal failure in Madagascar. This is a retrospective, descriptive study of 239 patients with chronic renal failure over a 3 year period, starting from 1 January 2007 to 31 December 2009, in the Department of Internal Medicine and Nephrology at University Hospital of Antananarivo. The incidence was 8.51% among patients hospitalized in the Department. The average age of patients was 45.4 years with extremes of 16 and 82 years and a sex ratio 1,46. The main antecedent was arterial hypertension (59.8%). Chronic renal failure was terminal in 75.31% of the cases (n=180). The causes of chronic renal failure were dominated by chronic glomerulonephritis (40.1%), nephroangiosclerosis (35.5%). Hemodialysis was performed in 3 patients (1.26%), no patient was scheduled for a renal transplantation. Mortality rate in the Department was 28.87%. Chronic renal failure is a debilitating disease with a dreadful prognosis which affects young patients in Madagascar. Its treatment remains inaccessible to the majority of patients. The focus must be mainly on prevention, especially on early effective management of infections, arterial hypertension and diabetes to reduce its negative impacts on the community and public health. The project on renal transplantation: living donor, effective and less expensive treatment compared to hemodialysis could also be a good solution for these Malagasy young subjects.

  9. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by medical...

  10. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of chronic renal disease. 79.57... disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... conclusion that a claimant developed chronic renal disease must be supported by medical documentation. (b) A...

  11. 28 CFR 79.67 - Proof of chronic renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of chronic renal disease. 79.67... renal disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... claimant. A conclusion that a claimant developed chronic renal disease must be supported by medical...

  12. 28 CFR 79.57 - Proof of chronic renal disease.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of chronic renal disease. 79.57... disease. (a) In determining whether a claimant developed chronic renal disease following pertinent... conclusion that a claimant developed chronic renal disease must be supported by medical documentation. (b) A...

  13. Midlife stress alters memory and mood-related behaviors in old age: Role of locally activated glucocorticoids.

    PubMed

    Wheelan, Nicola; Kenyon, Christopher J; Harris, Anjanette P; Cairns, Carolynn; Al Dujaili, Emad; Seckl, Jonathan R; Yau, Joyce L W

    2018-03-01

    Chronic exposure to stress during midlife associates with subsequent age-related cognitive decline and may increase the vulnerability to develop psychiatric conditions. Increased hypothalamic-pituitary-adrenal (HPA) axis activity has been implicated in pathogenesis though any causative role for glucocorticoids is unestablished. This study investigated the contribution of local glucocorticoid regeneration by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), in persisting midlife stress-induced behavioral effects in mice. Middle-aged (10 months old) 11β-HSD1-deficient mice and wild-type congenic controls were randomly assigned to 28 days of chronic unpredictable stress or left undisturbed (non-stressed). All mice underwent behavioral testing at the end of the stress/non-stress period and again 6-7 months later. Chronic stress impaired spatial memory in middle-aged wild-type mice. The effects, involving a wide spectrum of behavioral modalities, persisted for 6-7 months after cessation of stress into early senescence. Enduring effects after midlife stress included impaired spatial memory, enhanced contextual fear memory, impaired fear extinction, heightened anxiety, depressive-like behavior, as well as reduced hippocampal glucocorticoid receptor mRNA expression. In contrast, 11β-HSD1 deficient mice resisted both immediate and enduring effects of chronic stress, despite similar stress-induced increases in systemic glucocorticoid activity during midlife stress. In conclusion, chronic stress in midlife exerts persisting effects leading to cognitive and affective dysfunction in old age via mechanisms that depend, at least in part, on brain glucocorticoids generated locally by 11β-HSD1. This finding supports selective 11β-HSD1 inhibition as a novel therapeutic target to ameliorate the long-term consequences of stress-related psychiatric disorders in midlife. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Circuit and synaptic mechanisms of repeated stress: Perspectives from differing contexts, duration, and development.

    PubMed

    Bath, Kevin G; Russo, Scott J; Pleil, Kristen E; Wohleb, Eric S; Duman, Ronald S; Radley, Jason J

    2017-12-01

    The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was "Stress and the Synapse: New Concepts and Methods" and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress) on synaptic function, neurodevelopment, and behavioral outcomes. One of the goals of the symposium was to highlight the mechanisms accounting for how the nervous system responds to stress and their impact on outcome measures with converging effects on the development of pathological behavior. Dr. Kevin Bath's presentation focused on the impact of disruptions in early maternal care and its impact on the timing of hippocampus maturation in mice, finding that this form of stress drove accelerated synaptic and behavioral maturation, and contributed to the later emergence of risk for cognitive and emotional disturbance. Dr. Scott Russo highlighted the impact of chronic social defeat stress in adolescent mice on the development and plasticity of reward circuity, with a focus on glutamatergic development in the nucleus accumbens and mesolimbic dopamine system, and the implications of these changes for disruptions in social and hedonic response, key processes disturbed in depressive pathology. Dr. Kristen Pleil described synaptic changes in the bed nuclei of the stria terminalis that underlie the behavioral consequences of allostatic load produced by repeated cycles of alcohol binge drinking and withdrawal. Dr. Eric Wohleb and Dr. Ron Duman provided new data associating decreased mammalian target of rapamycin (mTOR) signaling and neurobiological changes in the synapses in response to chronic unpredictable stress, and highlighted the potential for the novel antidepressant ketamine to rescue synaptic and behavioral effects. In aggregate, these presentations showcased how divergent perspectives provide new insights into the ways in which stress impacts circuit development and function, with implications for understanding emergence of affective pathology.

  15. Population based screening for chronic kidney disease: cost effectiveness study.

    PubMed

    Manns, Braden; Hemmelgarn, Brenda; Tonelli, Marcello; Au, Flora; Chiasson, T Carter; Dong, James; Klarenbach, Scott

    2010-11-08

    To determine the cost effectiveness of one-off population based screening for chronic kidney disease based on estimated glomerular filtration rate. Cost utility analysis of screening with estimated glomerular filtration rate alone compared with no screening (with allowance for incidental finding of cases of chronic kidney disease). Analyses were stratified by age, diabetes, and the presence or absence of proteinuria. Scenario and sensitivity analyses, including probabilistic sensitivity analysis, were performed. Costs were estimated in all adults and in subgroups defined by age, diabetes, and hypertension. Publicly funded Canadian healthcare system. Large population based laboratory cohort used to estimate mortality rates and incidence of end stage renal disease for patients with chronic kidney disease over a five year follow-up period. Patients had not previously undergone assessment of glomerular filtration rate. Lifetime costs, end stage renal disease, quality adjusted life years (QALYs) gained, and incremental cost per QALY gained. Compared with no screening, population based screening for chronic kidney disease was associated with an incremental cost of $C463 (Canadian dollars in 2009; equivalent to about £275, €308, US $382) and a gain of 0.0044 QALYs per patient overall, representing a cost per QALY gained of $C104 900. In a cohort of 100 000 people, screening for chronic kidney disease would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 675 to 657. In subgroups of people with and without diabetes, the cost per QALY gained was $C22 600 and $C572 000, respectively. In a cohort of 100 000 people with diabetes, screening would be expected to reduce the number of people who develop end stage renal disease over their lifetime from 1796 to 1741. In people without diabetes with and without hypertension, the cost per QALY gained was $C334 000 and $C1 411 100, respectively. Population based screening for chronic kidney disease with assessment of estimated glomerular filtration rate is not cost effective overall or in subgroups of people with hypertension or older people. Targeted screening of people with diabetes is associated with a cost per QALY that is similar to that accepted in other interventions funded by public healthcare systems.

  16. Quantification of Urbanization in Relation to Chronic Diseases in Developing Countries: A Systematic Review

    PubMed Central

    Foster, Charlie; Hutchinson, Lauren; Arambepola, Carukshi

    2008-01-01

    During and beyond the twentieth century, urbanization has represented a major demographic shift particularly in the developed world. The rapid urbanization experienced in the developing world brings increased mortality from lifestyle diseases such as cancer and cardiovascular disease. We set out to understand how urbanization has been measured in studies which examined chronic disease as an outcome. Following a pilot search of PUBMED, a full search strategy was developed to identify papers reporting the effect of urbanization in relation to chronic disease in the developing world. Full searches were conducted in MEDLINE, EMBASE, CINAHL, and GLOBAL HEALTH. Of the 868 titles identified in the initial search, nine studies met the final inclusion criteria. Five of these studies used demographic measures (such as population density) at an area level to measure urbanization. Four studies used more complicated summary measures of individual and area level data (such as distance from a city, occupation, home and land ownership) to define urbanization. The papers reviewed were limited by using simple area level summary measures (e.g., urban rural dichotomy) or having to rely on preexisting data at the individual level. Further work is needed to develop a measure of urbanization that treats urbanization as a process and which is sensitive enough to track changes in “urbanicity” and subsequent emergence of chronic disease risk factors and mortality. Electronic supplementary material The online version of this article doi:10.1007/s11524-008-9325-4 contains supplementary material, which is available to authorized users. PMID:18931915

  17. Erythropoietin, but not the correction of anemia alone, protects from chronic kidney allograft injury.

    PubMed

    Cassis, Paola; Gallon, Lorenzo; Benigni, Ariela; Mister, Marilena; Pezzotta, Anna; Solini, Samantha; Gagliardini, Elena; Cugini, Daniela; Abbate, Mauro; Aiello, Sistiana; Rocchetta, Federica; Scudeletti, Pierangela; Perico, Norberto; Noris, Marina; Remuzzi, Giuseppe

    2012-05-01

    Anemia can contribute to chronic allograft injury by limiting oxygen delivery to tissues, particularly in the tubulointerstitium. To determine mechanisms by which erythropoietin (EPO) prevents chronic allograft injury we utilized a rat model of full MHC-mismatched kidney transplantation (Wistar Furth donor and Lewis recipients) with removal of the native kidneys. EPO treatment entirely corrected post-transplant anemia. Control rats developed progressive proteinuria and graft dysfunction, tubulointerstitial damage, inflammatory cell infiltration, and glomerulosclerosis, all prevented by EPO. Normalization of post-transplant hemoglobin levels by blood transfusions, however, had no impact on chronic allograft injury, indicating that EPO-mediated graft protection went beyond the correction of anemia. Compared to syngeneic grafts, control allografts had loss of peritubular capillaries, higher tubular apoptosis, tubular and glomerular oxidative injury, and reduced expression of podocyte nephrin; all prevented by EPO treatment. The effects of EPO were associated with preservation of intragraft expression of angiogenic factors, upregulation of the anti-apoptotic factor p-Akt in tubuli, and increased expression of Bcl-2. Inhibition of p-Akt by Wortmannin partially antagonized the effect of EPO on allograft injury and tubular apoptosis, and prevented EPO-induced Bcl-2 upregulation. Thus non-erythropoietic derivatives of EPO may be useful to prevent chronic renal allograft injury.

  18. Optimizing patient treatment decisions in an era of rapid technological advances: the case of hepatitis C treatment.

    PubMed

    Liu, Shan; Brandeau, Margaret L; Goldhaber-Fiebert, Jeremy D

    2017-03-01

    How long should a patient with a treatable chronic disease wait for more effective treatments before accepting the best available treatment? We develop a framework to guide optimal treatment decisions for a deteriorating chronic disease when treatment technologies are improving over time. We formulate an optimal stopping problem using a discrete-time, finite-horizon Markov decision process. The goal is to maximize a patient's quality-adjusted life expectancy. We derive structural properties of the model and analytically solve a three-period treatment decision problem. We illustrate the model with the example of treatment for chronic hepatitis C virus (HCV). Chronic HCV affects 3-4 million Americans and has been historically difficult to treat, but increasingly effective treatments have been commercialized in the past few years. We show that the optimal treatment decision is more likely to be to accept currently available treatment-despite expectations for future treatment improvement-for patients who have high-risk history, who are older, or who have more comorbidities. Insights from this study can guide HCV treatment decisions for individual patients. More broadly, our model can guide treatment decisions for curable chronic diseases by finding the optimal treatment policy for individual patients in a heterogeneous population.

  19. Gastrocnemius recession for recalcitrant plantar fasciitis in overweight and obese patients.

    PubMed

    Ficke, Brooks; Elattar, Osama; Naranje, Sameer M; Araoye, Ibukunoluwa; Shah, Ashish B

    2017-06-07

    Plantar fasciitis is a common foot pathology that is typically treated non-operatively. However, a minority of patients fail non-operative management, develop chronic symptoms, and request a surgical option. Gastrocnemius recession has recently been shown to be effective for the treatment of chronic plantar fasciitis. The purpose of this paper is to present evidence that gastrocnemius recession is safe and effective in the subset of chronic plantar fasciitis patients who are overweight and obese. We retrospectively reviewed 18 cases (17 patients) of chronic plantar fasciitis in overweight or obese patients who underwent gastrocnemius recession (mean age=46years, mean body mass index=34.7kg/m 2 , mean follow-up=20months). Data was gathered regarding pre-operative and post-operative pain (visual analog scale, 0-10), Foot Function Index score, and complications. Mean Foot Function Index score improved from 66.4 (range, 32.3-97.7) preoperatively to 26.5 (range, 0-89.4) postoperatively (p<0.01). Mean pain score improved from 8.3 (range, 5-10) preoperatively to 2.4 (range, 0-7) at final follow-up (p<0.01). Gastrocnemius recession improved foot function and pain symptoms in overweight and obese patients with chronic plantar fasciitis. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  20. Optimizing Patient Treatment Decisions in an Era of Rapid Technological Advances: The Case of Hepatitis C Treatment

    PubMed Central

    Liu, Shan; Goldhaber-Fiebert, Jeremy D.; Brandeau, Margaret L.

    2015-01-01

    How long should a patient with a treatable chronic disease wait for more effective treatments before accepting the best available treatment? We develop a framework to guide optimal treatment decisions for a deteriorating chronic disease when treatment technologies are improving over time. We formulate an optimal stopping problem using a discrete-time, finite-horizon Markov decision process. The goal is to maximize a patient’s quality-adjusted life expectancy. We derive structural properties of the model and analytically solve a three-period treatment decision problem. We illustrate the model with the example of treatment for chronic hepatitis C virus (HCV). Chronic HCV affects 3–4 million Americans and has been historically difficult to treat, but increasingly effective treatments have been commercialized in the past few years. We show that the optimal treatment decision is more likely to be to accept currently available treatment—despite expectations for future treatment improvement—for patients who have high-risk history, who are older, or who have more comorbidities. Insights from this study can guide HCV treatment decisions for individual patients. More broadly, our model can guide treatment decisions for curable chronic diseases by finding the optimal treatment policy for individual patients in a heterogeneous population. PMID:26188961

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