Epigenetic and miRNA Expression Changes in People with Pain: A Systematic Review

Accumulating evidence suggests that epigenetic mechanisms may hold great potential in the field of pain. We systematically reviewed the literature exploring epigenetic mechanisms in people with pain. Four databases have been interrogated: MEDLINE, The Cochrane Central Register of Controlled Trial, Scopus, and Web of Science, following PRISMA guidelines in conducting study selection and assessment. Thirty-seven studies were included. Studies explored epigenetics in conditions such as fibromyalgia, CRPS, neuropathies, or osteoarthritis. Research focussed on genome-wide and gene-specific DNA methylation, and miRNA expression. Bioinformatics analyses exploring miRNA-associated molecular pathways were also performed. Several genes already known for their role in pain (BDNF, HDAC4, PRKG1, IL-17, TNFRSF13B, etc.), and several miRNAs linked to inflammatory regulation, nociceptive signalling and protein kinases functions have been found to differ significantly between people with chronic pain and healthy controls. Although the studies included were cross-sectional in nature, and no conclusion on causal links between epigenetic changes and pain could be drawn, we summarised the large amount of data available in literature on the topic, highlighting results that have been replicated by independent investigations. The field of pain epigenetics appears very exciting and has all the potential to lead to remarkable scientific advances. However, high-quality, well-powered, longitudinal studies are warranted.PerspectiveThough more high-quality research is needed, available research exploring epigenetic mechanisms or miRNAs in people with pain shows that genes regulating synaptic plasticity and excitability, protein kinases, and elements of the immune system might hold great potential in understanding the pathophysiology of different conditions.     

Perceived Short- and Long-Term Effects of Bereavement Support Group Participation at the Hospice of Petaluma

Fatigue is a symptom that is frequently found in chronic pain patients with low back pain and/or neck pain. At the present time, no specific psychopharmacological treatment for this problem has been identified. Modafinil is a wakefulness-promoting agent that the FDA has approved for the treatment of excessive daytime sleepiness associated with narcolepsy. There have been reports on the use of modafinil for the treatment of fatigue in various neurological syndromes. This literature is reviewed. As such, modafinil treatment was initiated for a patient with severe fatigue associated with chronic low back pain and neck pain. There was dramatic improvement in fatigue and associated function. This case is described. It is the first such case report in the literature. The significance of this finding to the treatment of pain-associated fatigue is discussed.     

Modafinil for the treatment of pain-associated fatigue: review and case report

Fatigue is a symptom that is frequently found in chronic pain patients with low back pain and/or neck pain. At the present time, no specific psychopharmacological treatment for this problem has been identified. Modafinil is a wakefulness-promoting agent that the FDA has approved for the treatment of excessive daytime sleepiness associated with narcolepsy. There have been reports on the use of modafinil for the treatment of fatigue in various neurological syndromes. This literature is reviewed. As such, modafinil treatment was initiated for a patient with severe fatigue associated with chronic low back pain and neck pain. There was dramatic improvement in fatigue and associated function. This case is described. It is the first such case report in the literature. The significance of this finding to the treatment of pain-associated fatigue is discussed.     

外周T细胞淋巴瘤的表观遗传机制及治疗进展

外周T细胞淋巴瘤(PTCL)是一组高度异质且预后极差的恶性肿瘤,基因异常和分子生物学改变是其发生、发展的重要因素.目前,PTCL的治疗仍然借鉴侵袭性B细胞淋巴瘤的化疗方案,但是疗效并不显著.表观遗传学作为一门涉及基因表达调控的新兴学科,为PTCL的发生、发展机制的研究与临床诊断治疗提供了新的思路.同时,针对PTCL的新型表观遗传学靶向药物的研发及新药联合应用方案的研究亦在进行中.因此,表观遗传学调控为PTCL的诊断及治疗提供了新的治疗切入点.笔者拟就PTCL的表观遗传学机制研究及相关靶向新药的应用前景进行综述.     

The challenge of evaluating fatigue

Fatigue, though a common complaint, presents a challenge to nurse practitioners who must evaluate its significance in the primary care setting. Fatigue is described as a multidimensional phenomenon and is classified as physiologic, acute, or chronic. A distinction is made between chronic fatigue and chronic fatigue syndrome (CFS). The use of the Piper Fatigue Scale is suggested in order to objectively quantify this symptom in clinical practice. In this article, the Habit and Lifestyle Form for the Evaluation of Fatigue is presented as a way to assist the provider in considering simple and obvious causes of fatigue that may otherwise be overlooked. Finally, an algorithm for the evaluation of fatigue is presented.     

Psychometric Properties of Instruments Used to Measure Fatigue in Children and Adolescents With Cancer: A Systematic Review

ContextDespite the recognized distressing symptom of fatigue in children with cancer, little information is available to assist in the selection of an instrument to be used to measure fatigue.ObjectivesThe objectives of this study were to 1) describe the instruments that have been used to measure cancer-related fatigue in children and adolescents and 2) summarize the psychometric properties of the most commonly used instruments used to measure fatigue in children and adolescents with cancer.MethodsFive major electronic databases were systematically searched for studies using a fatigue measurement scale in a population of children or adolescents with cancer. Fatigue scales used in those studies were included in the review.ResultsFrom a total of 1753 articles, 25 were included. We identified two main fatigue measurement instruments used in a pediatric oncology population: 1) the Fatigue Scale-Child/Fatigue Scale-Adolescent and the proxy report versions for parents and staff and 2) the PedsQL? Multidimensional Fatigue Scale. These two scales show similar attributes with reasonably good internal consistency and responsiveness.ConclusionEither the Fatigue Scale or PedsQL Multidimensional Fatigue Scale can be incorporated into clinical research. Future research should focus on identifying specific fatigue measures more suited to different purposes such as comparative trials or identification of high-risk groups.     

The Measurement of Fatigue in Chronic Illness: A Systematic Review of Unidimensional and Multidimensional Fatigue Measures

Fatigue is a common symptom associated with a wide range of chronic diseases. A large number of instruments have been developed to measure fatigue. An assessment regarding the reliability, validity, and utility of fatigue measures is time-consuming for the clinician and researcher, and few reviews exist on which to draw such information. The aim of this article is to present a critical review of fatigue measures, the populations in which the scales have been used, and the extent to which the psychometric properties of each instrument have been evaluated to provide clinicians and researchers with information on which to base decisions. Seven databases were searched for all articles that measured fatigue and offered an insight into the psychometric properties of the scales used over the period 1980–2007. Criteria for judging the “ideal” measure were developed to encompass scale usability, clinical/research utility, and the robustness of psychometric properties. Twenty-two fatigue measures met the inclusion criteria and were evaluated. A further 17 measures met some of the criteria, but have not been tested beyond initial development, and are reviewed briefly at the end of the article. The review did not identify any instrument that met all the criteria of an ideal instrument. However, a small number of short instruments demonstrated good psychometric properties (Fatigue Severity Scale [FSS], Fatigue Impact Scale [FIS], and Brief Fatigue Inventory [BFI]), and three comprehensive instruments demonstrated the same (Fatigue Symptom Inventory [FSI], Multidimensional Assessment of Fatigue [MAF], and Multidimensional Fatigue Symptom Inventory [MFSI]). Only four measures (BFI, FSS, FSI, and MAF) demonstrated the ability to detect change over time. The clinician and researcher also should consider the populations in which the scale has been used previously to assess its validity with their own patient group, and assess the content of a scale to ensure that the key qualitative aspects of fatigue of the population of interest are covered.     

Fatigue and rheumatoid arthritis.

Fatigue is a common complaint among patients with rheumatoid arthritis (RA) and is regarded as an extra-articular symptom of the disease. Little attention has been paid by health professional teams to the multidimensional nature of RA-related fatigue and its wide-ranging consequences for quality of life. Unlike normal tiredness, fatigue is chronic, typically not related to overexertion and poorly relieved by rest. The prevalence is high and several RA-related components have been reported as predictors of fatigue. RA-related fatigue appeared to be strongly associated with psychosocial factors. Fatigue assessment and management are complex because psychological and physiological factors may be involved. Several instruments that have been used in RA to assess fatigue. They have involved a self-reporting format. Some are brief, quantitative and symptom-focused questionnaires. Others provide a multidimensional assessment. DMARD therapy, especially anti-TNF decreased disease activity and alleviates fatigue. An additional direct effect is hypothetical. The non-pharmacological management includes behavioral therapy or self-management courses and physical exercise. Finally, the importance and relevance of fatigue as an outcome measure is becoming highlighted by research groups and should lead to improved management of fatigue in usual medical practice.     

表观遗传调控在白血病发生中作用的研究进展——MicroRNA与白血病

表观遗传是指DNA序列不发生变化但基因的表达却发生了可遗传的改变,表观遗传调控与白血病的发生密切相关。随着发现一类新的非编码的微小RNA(microRNA)参与基因表达的转录后和翻译水平的调节,异常的microRNA的表达在白血病的发生中起着重要的作用。作为表观遗传研究范畴的microRNA,已成为了白血病发病机制中的异常表观遗传调控研究的新热点。本文就表现遗传调控与白血病的发生、miRNA的表达异常在白血病发生中的作用、miRNA在白血病诊断、分类、治疗和预后判断中的应用前景进行了综述。     

Neuroendocrine and Immune Contributors to Fatigue

Central fatigue, a persistent and subjective sense of tiredness, generally correlates poorly with traditional markers of disease. It is frequently associated with psychosocial factors, such as depression, sleep disorder, anxiety, and coping style, which suggest that dysregulation of the body's stress systems may serve as an underlying mechanism in the maintenance of chronic fatigue (CF). This article addresses the endocrine, neural, and immune factors that contribute to fatigue and describes research regarding the role of these factors in chronic fatigue syndrome as a model for addressing the biology of CF. In general, hypoactivity of the hypothalamic-pituitary-adrenal axis, autonomic nervous system alterations characterized by sympathetic overactivity and low vagal tone, as well as immune abnormalities, may contribute to the expression of CF. Noninvasive methods for evaluating endocrine, neural, and immune function are also discussed. Simultaneous evaluation of neuroendocrine and immune systems with noninvasive techniques will help elucidate the underlying interactions of these systems, their role in disease susceptibility, and progression of stress-related disorders.     

Fatigue in chronic illness: the experience of individuals with chronic obstructive pulmonary disease and with asthma

Although fatigue has been identified as a major problem for individuals with chronic obstructive pulmonary disease and with asthma, no research was found in which the symptom was directly studied in persons with these conditions. From studies carried out on various patient populations, it appears that fatigue has some specificity to disease state. Thus, it is important to describe the experience of fatigue within patient populations. To expand theoretical understanding of fatigue, qualitative research methods need to be applied. The purpose of this study therefore was to describe and compare the fatigue experiences of persons with chronic obstructive pulmonary disease (n=17) and with asthma (n=19). Data were obtained by use of a semi-structured questionnaire and were content analysed for categories and themes. There were many similarities between the fatigue experiences of the two groups. Fatigue is inextricably linked to laboured breathing. Although it interferes with their ability to carry out meaningful activities, the majority of individuals with chronic obstructive pulmonary disease or asthma cope well with it. The informants identified two types of coping strategies they use to manage their situation, which may be categorized as: problem-focused, including energy conservation, utilization and restoration; and emotion-focused, including being positive, accepting the physical limitations, distracting and normalizing.     

Fatigue after stroke: relationship to mobility, fitness, ambulatory activity, social support, and falls efficacy.

Fatigue is common and persistent in stroke survivors, yet it is not known how mobility deficits, fitness, or other factors, such as social support, relate to fatigue severity, or whether subjective fatigue contributes to reduced ambulatory activity. The severity of fatigue in a sample of 53 community-dwelling subjects with chronic hemiparetic stroke was examined, and relationships among fatigue and mobility deficit severity, cardiovascular-metabolic fitness, ambulatory activity, social support, and self-efficacy for falls were identified. Measures included the Fatigue Severity Scale, timed 10-meter walks, the Berg Balance Scale, submaximal and peak VO2, total daily step activity derived from microprocessor-linked Step Activity Monitors, the Medical Outcomes Study Social Support Survey, and the Falls Efficacy Scale. Forty-six percent of the sample had severe fatigue. Fatigue showed no relationship to ambulatory activity. Fatigue severity was associated with the Berg Balance Scale (p < .01) and falls efficacy (p < .01), but not with cardiovascular fitness variables. Patients with elevated fatigue severity scores had lower social support (p < .05) and poorer falls efficacy scores (p < .05) than patients reporting less fatigue. Only falls efficacy was predictive of fatigue severity (r2 = 0.216, p < .01). Further studies are needed to evaluate whether rehabilitation strategies that include not only fitness and mobility interventions, but also social/behavioral and self-efficacy components, are associated with reduced fatigue and increased ambulation.     

Fatigue associated with stroke and other neurologic conditions: Implications for stroke rehabilitation

OBJECTIVES: To examine the general phenomenon of fatigue in stroke and other neurologic disorders and to review what is currently known about its occurrence, including its frequency, duration, severity, and associated factors, to develop a strategy for treatment. DATA SOURCES: Computerized databases (eg, PubMed, PsycInfo, Science Citation Index, Ovid EMBASE, Ovid MEDLINE) searched from inception to May 2002. Additional references were identified from bibliographies of pertinent articles and books. STUDY SELECTION: Over 1000 articles were identified as relevant to fatigue experienced by patients with neurologic or nonneurologic disorders. Articles on fatigue in stroke and neurologic disorders, mechanisms, and/or treatment were selected for inclusion. DATA EXTRACTION: Authors reviewed the articles and assessed the purpose, study design, and conclusions for validity and relevance to the topic of fatigue in stroke. DATA SYNTHESIS: Fatigue is a common complaint among patients with neurologic disorders including stroke. Few studies have documented the high frequency of fatigue in poststroke patients and its negative impact on daily functioning and quality of life. Little is known about associated factors or about therapeutic strategies that may be used to alleviate it. Examination of fatigue in other neurologic populations suggests common characteristics and associated factors that may be useful in the development of potential therapeutic strategies. Pharmacologic and nonpharmacologic therapeutic interventions, such as stimulants, amantadine, or sleep and stress-management education, have been used with some success in neurologic and other patient populations (eg, multiple sclerosis, human immunodeficiency virus, acquired immune deficiency syndrome, cancer), but evidence of effectiveness based on randomized clinical trials is rare. CONCLUSIONS: Poststroke fatigue is common. Therapeutic strategies have been used to treat fatigue in other patient populations, but it is unclear whether these will be beneficial to poststroke patients. Frequency, severity, duration, impact, predisposing factors, and causes of poststroke fatigue, as well as the development of effective treatment, require further research. Criteria for assessment of fatigue and potential therapeutic interventions are outlined as a first step for stimulating further research.     

Fatigue in palliative care patients -- an EAPC approach

Fatigue is one of the most frequent symptoms in palliative care patients, reported in .80% of cancer patients and in up to 99% of patients following radio- or chemotherapy. Fatigue also plays a major role in palliative care for noncancer patients, with large percentages of patients with HIV, multiple sclerosis, chronic obstructive pulmonary disease or heart failure reporting fatigue.This paper presents the position of an expert working group of the European Association for Palliative Care (EAPC), evaluating the available evidence on diagnosis and treatment of fatigue in palliative care patients and providing the basis for future discussions. As the expert group feels that culture and language influence the approach to fatigue in different European countries, a focus was on cultural issues in the assessment and treatment of fatigue in palliative care. As a working definition, fatigue was defined as a subjective feeling of tiredness, weakness or lack of energy. Qualitative differences between fatigue in cancer patients and in healthy controls have been proposed, but these differences seem to be only an expression of the overwhelming intensity of cancer-related fatigue. The pathophysiology of fatigue in palliative care patients is not fully understood. For a systematic approach, primary fatigue, most probably related to high load of proinflammatory cytokines and secondary fatigue from concurrent syndromes and comorbidities may be differentiated. Fatigue is generally recognized as a multidimensional construct, with a physical and cognitive dimension acknowledged by all authors. As fatigue is an inherent word only in the English and French language, but not in other European languages, screening for fatigue should include questions on weakness as a paraphrase for the physical dimension and on tiredness as a paraphrase for the cognitive dimension. Treatment of fatigue should include causal interventions for secondary fatigue and symptomatic treatment with pharmacological and nonpharmacological interventions. Strong evidence has been accumulated that aerobic exercise will reduce fatigue levels in cancer survivors and patients receiving cancer treatment. In the final stage of life, fatigue may provide protection and shielding from suffering for the patient and thus treatment may be detrimental. Identification of the time point, where treatment of fatigue is no longer indicated is important to alleviate distress at the end of life.     

The fatigue experience: persons with HIV infection

Fatigue is a frequently reported symptom by persons with HIV infection and one that has an adverse impact on activities of daily living and overall quality of life. Although the concept of fatigue has been studied extensively and discussed in the literature, little is known about the experience of fatigue by persons with HIV infection. A hermeneutic phenomenological study was conducted to investigate the subjective experience of HIV-associated fatigue and to describe the management of fatigue in the context of daily life. In-depth interviews were done with 10 adult patients of an outpatient HIV/AIDS clinic. Thematic analysis identified three concerns that represented the meaning of fatigue for the participants. The first concern was 'Fatigue as a signal of AIDS'. A second concern was 'The mind, the body, the social experience of fatigue'. The third concern was 'Choosing ways to live with fatigue and addiction'. The findings provide insights for nursing practice regarding the subjective meaning of fatigue for patients with HIV and the need for nurses to explore this topic with patients.     

Modèle animaux d’obésité

Animal models provide major contribution to our understanding of the physiological, environmental, genetic and epigenetic bases of obesity. Most rodent models of obesity have been investigated since the early fifties, but it??s only more recently that the mechanisms underlying their phenotype were identified, thanks to the development of molecular biology. This article reviews various models of rodent obesity, naturally occurring or created by researchers: nutritional obesity induced by a high fat diet, hypothalamic obesity resulting from lesions in areas controlling food intake and genetic obesity due to spontaneous mutations in crucial genes for energy balance, such as leptin and leptin receptor genes. Each model provides information related to specific aspects of human obesity, particularly in the field of monogenic obesities that are rare but often severe as in leptin-deficient patients. Models of obese rodents represent precious and necessary tools to explore the complexity of energy balance regulation and for innovative therapeutic intervention in obesity, of which the success of leptin treatment for leptin-deficient patients is a striking example.     

恶性血液病的表观遗传学研究进展

表观遗传学是研究可遗传的、基因DNA序列不发生改变的基因表达调控的一门新学科.近年来,诸多研究结果均表明,表观遗传学异常改变在恶性血液病的发生、发展过程中起着十分重要的作用.相关基因异常甲基化是骨髓增生异常综合征(MDS)发生、发展的重要因素之一,并且与MDS患者的预后相关;微小RNA (miRNA)的异常甲基化与急性髓细胞白血病(AML)相关;zeste基因增强子同源物(EZH)2基因通过突变、缺失或过表达,甲基化下游靶基因调控其转录水平,从而与淋巴瘤等多种恶性血液病相关.针对表观遗传学异常改变的治疗方案给恶性血液病的免疫治疗赋予更广的内涵.笔者拟就表观遗传学异常改变在恶性血液病中的最薪研究进展,以及针对表观遗传学异常改变的免疫治疗方案的相关研究与应用前景进行综述.     

Complex disease, gender and epigenetics

Gender differences in susceptibility to complex disease such as asthma, diabetes, lupus, autism and major depression, among numerous other disorders, represent one of the hallmarks of non-Mendelian biology. It has been generally accepted that endocrinological differences are involved in the sexual dimorphism of complex disease; however, specific molecular mechanisms of such hormonal effects have not been elucidated yet. This paper will review evidence that sex hormone action may be mediated via gene-specific epigenetic modifications of DNA and histones. The epigenetic modifications can explain sex effects at DNA sequence polymorphisms and haplotypes identified in gender-stratified genetic linkage and association studies. Hormone-induced DNA methylation and histone modification changes at specific gene regulatory regions may increase or reduce the risk of a disease. The epigenetic interpretation of sexual dimorphism fits well into the epigenetic theory of complex disease, which argues for the primary pathogenic role of inherited and/or acquired epigenetic misregulation rather than DNA sequence variation. The new experimental strategies, especially the high throughput microarray-based epigenetic profiling, can be used for testing the epigenetic hypothesis of gender effects in complex diseases.