The importance of understanding how our genes change

Extract from article by Cort Johnson:

Epigenetics refers to the changes in sites in our DNA that are susceptible to change over time which can modify the expression of our genes.  Our genetic heritage, it turns out, only sets the tableau for how our genes express themselves. Just because you’re borne with a genetic  makeup that suggests, say, your immune system will immediately jump on and take out any pathogen that dares disturb you, that doesn’t mean it’s going to stay that way.

Epigenetics has provided an entirely new slant on genetics and gene expression. Things happen as you age that will change how your genes respond to events. Epigenetics isn’t so much an ‘if’ as it is a ‘how much’.  These processes occur in our body all the time. The older we get the less we are our mother’s and father’s sons and daughters and the more our genetic makeup takes on an identity of its own.

Twin studies indicating identical twins are epigenetically indistinguishable at first but diverge widely over time indicate how malleable our patterns of gene expression are. How this change in gene expression over time occurs and the implications it has for health and disease is what epigenetics is all about.  In a short time it’s become an enormous field. There’s no question epigenetic modifications play a role in  disease – the only question is how much of a role.

A couple of years ago the National Institutes of Health was interested enough in the possible effects of epigenetic changes on aging, heart disease, and mental illness to devote 190 million dollars to its study. Some researchers think epigenetics will end up having a greater impact on disease than genetics.

Epigenetic modifications of immune genes have been implicated in autoimmune and other inflammatory diseases as well as neurodegenerative diseases. Researchers are now arguing which factor – genes, the environment, or epigenetics – plays the biggest role in autoimmunity.  A recent review paper described probable epigenetic effects on neuroinflammation…

Cort goes on to discuss research findings for changes in gene expression in CFS (referring to Patrick McGowan’s research), FM and Rheumatic diseases, and the issues for future research: Epigenetics Study Highlights Immune Issues in Chronic Fatigue Syndrome 

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How Corinne built a house without harmful chemicals

Flame retardants, formaldehyde and volatile organic compounds shouldn’t be in any of our houses, but for those with Multiple Chemical Sensitivities (MCS), they are a disaster. The tiny house concept has been a godsend for not a few people suffering from MCS, Chronic Fatigue Syndrome (CFS/ME), Fibromyalgia and other auto-immune illnesses; it gives them a chance to live in a home that is built without any of the paints, glues, plastics and chemicals that they react to, usually in a place far away from pollution and other irritants.

It’s not easy to do. Corinne suffers from severe reactions to chemicals, and built her own tiny house out of carefully selected and tested materials. It is a lovely modern design, but it is also really healthy. She not only researched all the materials, tested them, and built a house out of them, but she has created a terrific blog documenting it, with extensive resources for others suffering from the same sensitivities. None of this was easy.

Read more: Woman builds herself a gorgeous, tiny, healthy, “chemical free” house

 

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ME Cover up – Severe ME Day August 8th 2014

the ME cover up

Many people with ME feel they are invisible to the outside world and that ME is not taken seriously.

“We may not be able to present ourselves to the world because of severe ill health but we want to be listened to and heard by the appropriate authorities and to receive services, and appropriate help.

We would also like to see more biomedical research undertaken, and cognisance taken of the body of biomedical research that exists at present.

We want the medical profession and general public to understand the seriousness of the illness and remember that underneath the sheet there is still a human being.”

 

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DSQ is valid tool for assessing symptoms in ME/CFS

Abstract

Background:

The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is complex and largely based on self-reported symptom profiles. The field lacks consensus for a singular case definition and heterogeneous samples make comparability across studies difficult.

Purpose:

The present study sought to validate a comprehensive self-report measure of ME/CFS symptomatology to aid in clinical and research assessment.

Methods:

Exploratory factor analysis (EFA) was used to establish the underlying factor structure of the DePaul Symptom Questionnaire (DSQ) using a well-characterized sample of individuals (92.6% met the Fukuda et al. criteria and/or the Clinical Canadian Criteria) and this structure was then tested on a less stringently recruited sample of individuals utilizing a confirmatory factor analysis (CFA). Convergent and discriminant validity of the DSQ were also examined utilizing alternative measures of symptomatology and functioning.

Results:

A three-factor solution was found using EFA (Neuroendocrine, Autonomic, and Immune Symptoms; Neurological/Cognitive Dysfunction; Post-Exertional Malaise) and the fit of this factor structure was adequate for the second sample. The DSQ was found to have good convergent and discriminant validity.

Conclusions:

The DSQ is a valid tool for assessing ME/CFS symptoms. There may be two core ME/CFS symptom clusters: post-exertional malaise and cognitive dysfunction.

Validating a measure of myalgic encephalomyelitis/chronic fatigue syndrome symptomatology by Abigail A. Brown & Leonard A. Jason in Fatigue: Biomedicine, Health & Behavior Volume 2, Issue 3, 2014

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Is CFS an autoimmune disorder with vasoactive neuropeptide dysfunction?

Abstract

Chronic fatigue syndrome is a disorder characterised by prolonged fatigue and debility and is mostly associated with post-infection sequelae although ongoing infection is unproven.

Immunological aberration is likely and this may prove to be associated with an expanding group of vasoactive neuropeptides in the context of molecular mimicry and inappropriate immunological memory.

Vasoactive neuropeptides including vasoactive intestinal peptide (VIP) and pituitary adenylate activating polypeptide (PACAP) belong to the secretin/glucagon superfamily and act as hormones, neurotransmitters, immune modulators and neurotrophes. They are readily catalysed to smaller peptide fragments by antibody hydrolysis. They and their binding sites are immunogenic and are known to be associated with a range of autoimmune conditions.

Vasoactive neuropeptides are widely distributed in the body particularly in the central, autonomic and peripheral nervous systems and have been identified in the gut, adrenal gland, reproductive organs, vasculature, blood cells and other tissues. They have a vital role in maintaining vascular flow in organs, and in thermoregulation, memory and concentration. They are co-transmitters for acetylcholine, nitric oxide, endogenous opioids and insulin, are potent immune regulators with primarily anti-inflammatory activity, and have a significant role in protection of the nervous system to toxic assault, promotion of neural development and the maintenance of homeostasis.

This paper describes a biologically plausible mechanism for the development of CFS based on loss of immunological tolerance to the vasoactive neuropeptides following infection, significant physical exercise or de novo. It is proposed that release of these substances is accompanied by a loss of tolerance either to them or their receptor binding sites in CFS. Such an occurrence would have predictably serious consequences resulting from compromised function of the key roles these substances perform.

All documented symptoms of CFS are explained by vasoactive neuropeptide compromise, namely fatigue and nervous system dysfunction through impaired acetylcholine activity, myalgia through nitric oxide and endogenous opioid dysfunction, chemical sensitivity through peroxynitrite and adenosine dysfunction, and immunological disturbance through changes in immune modulation.

Perverse immunological memory established against these substances or their receptors may be the reason for the protracted nature of this condition. The novel status of these substances together with their extremely small concentrations in blood and tissues means that clinical research into them is still in its infancy.

A biologically plausible theory of CFS causation associated with vasoactive neuropeptide dysfunction would promote a coherent and systematic approach to research into this and other possibly associated disabling conditions.

Is chronic fatigue syndrome an autoimmune disorder of endogenous neuropeptides, exogenous infection and molecular mimicry? by DR Staines in Med Hypotheses; 62(5): 646-52, 2004.

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‘Flowers’ in the blood – abnormally shaped red blood cells in CFS

CASE REPORT Abstract

 

Introduction:

Chronic fatigue syndrome is a debilitating condition characterized by persistent fatigue, post-exertional malaise, myalgia, arthralgia, lymph node tenderness, impaired memory and concentration, autonomic irregularities, and other specific symptoms affecting multiple body systems.

Diverse hypotheses have been investigated to ascertain the disease etiology. Some of these include metabolic and mitochondrial deficiencies, exposure to environmental toxins, dysautonomia associated with orthostatic intolerance, autoimmune reactions, neuroendocrine aberrations, and chronic viral infections.

However, a consistently observed biomarker for chronic fatigue has not been identified. A comprehensive, standardized strategy for accurate diagnosis and successful treatment remains elusive.

 

Case Report:

A 28-year-old Caucasian female presented with chronic fatigue persisting for nine months following infectious mononucleosis.

Laboratory evaluation excluded classic causes of fatigue. Peripheral blood smear examination revealed numerous pairs of unusual nondiscocytic C-shaped erythrocytes [red blood cells], coupled in perpendicular crosses resembling four-petalled flowers.

The presence of the erythrocyte pairs abated with the patient’s recovery from chronic fatigue syndrome over a 24-month period. This erythrocyte arrangement has not been reported elsewhere in medical literature.

Conclusion:

A novel erythrocyte “flower” formation was identified in a patient with chronic fatigue syndrome. The presence of this arrangement paralleled the course of the illness and was no longer observed upon recovery.

The physiological relevance of the structure remains a subject for future research. Several hypotheses are suggested, including enhanced membrane deformability resulting from elevated catecholamine levels, and immunemediated agglutination, possibly stemming from viral infection.

 

“Flowers” in the blood: A novel paired erythrocyte arrangement in a patient with chronic fatigue syndrome following infectious mononucleosis by Carrie E Burdzinski, in Int J Case Rep Images 2014 [provisional article]

NB Dr Les Simpson from New Zealand reported in the 1980s about his discovery of abnormally shaped blood cells in people with ME.

Nondiscocytic erythrocytes in myalgic encephalomyelitis

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Take responsibility for your own health says Health Minister

In a speech today, Mark Drakeford will call on the people of Wales to become ‘custodians’ of their own health

A “new bargain” needs to be struck between the people of Wales and the health service if the NHS is to continue to to thrive during and beyond the age of austerity, Health Minister Mark Drakeford will warn today.

Speaking at the NHS Confederation’s conference in Liverpool, Prof Drakeford will call on people in Wales to take more responsibility for their own health, instead of merely handing over ownership of their problems to the health service to deal with. He will say that while it is the role of the Welsh Government to create the right conditions for people to live healthier lives, members of the public must take advantage of this and fulfil their “duty” to look after themselves, becoming “custodians” of their own health.

He will tell delegates: “Governments have a responsibility to create the right conditions in which individuals can live full and healthy lives, taking responsibility for their own health.

“Each of us has a duty to look after ourselves – we must all become custodians of our own health, instead of handing ownership of our health to the nearest professional as we have traditionally done. “The NHS is there to help us in our time of need but with that comes a responsibility to use its resources wisely. The NHS is free from charge but not free from obligation.

“This then is the new bargain in this ongoing age of austerity – it is the bargain of co-production at an individual and population level. “At an individual level, the health professional and patient must work together, rather than the patient putting their health problem in the hand of the nurse, GP or consultant. The conversation we have with patients cannot always open with the question ‘What can I do for you?’ as though the encounter is one in which the health service takes onto its own shoulders the whole of the responsibility for that encounter.

“On a population level, the new bargain means that everyone accepts responsibility for their own health and a responsibility for managing demand on the NHS while the Welsh Government helps create an environment where it is easier to make healthier decisions while also safeguarding an NHS which remains firm to Bevan’s founding principles of universality, equity and free at the point of delivery.”

His comments come just weeks after the latest Welsh Health Survey showed the number of adults classed as overweight or obese stands at 58%, with 22% of people in the “obese” category alone. Meanwhile, the number of people drinking more alcohol than recommended stands at 42% and 26% of people admit binge-drinking. Just 29% of people do 30 minutes of exercise five times a week and only 33% of people eat five fruit or vegetables a day. But the survey showed some progress in tackling the rates of smoking as prevalence fell from 23% to 21% between 2012 and 2013.

Prof Drakeford’s speech will also echo his commitment to the idea of prudent healthcare, which he first outlined in January and follows the principle that the NHS should focus on what would work best for patients and make the most effective use of available resources.

He is set to highlight examples of where Wales has led the way in terms of improving public health including becoming the first in the UK to vote in favour of banning smoking in enclosed public places and introducing a mandatory food hygiene rating scheme.

He will also point to further proposals outlined in the Welsh Government’s public health white paper, which was published earlier this year. The measures include the introduction of a minimum price for alcohol of 50p per unit to tackle alcohol-related harm and for Wales to become the first in the UK to introduce a ban on e-cigarettes in public places.

Other proposals, which will be subject to consultation until June 24, include whether to make it an offence to deliver a tobacco product ordered online to someone under 18, even if the item was ordered by an adult, and introducing a national register for businesses providing cosmetic piercing, tattooing, semi-permanent skin colouring, acupuncture and electrolysis hair removal.

He will say: “Wales has a strong history of responding to citizens’ concerns and introducing practical regulations which make a positive contribution to protecting health “Taking concerted, collective action to address public health concerns remains one of the most powerful contributions any government can make to the welfare and wellbeing of its population. And I’m very proud that Wales has a long and progressive tradition when it comes to taking action to protect public health in Wales.

“For the nay-sayers, any attempt to protect public health is met with the inevitable cries of nanny-statism but our proposals, such as those outlined in our public health white paper, take a preventative approach by seeking to intervene at points which have most potential for long-term benefits, both in the health of individuals and in helping avoid higher, long-term societal and financial costs associated with avoidable ill health.”

New bargain’ to be struck between public and health service for NHS to thrive in austerity, warns Health Minister Mark Drakeford by Julia McWatt in Wales Online

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Do coping strategies improve health in CFS?

Abstract

OBJECTIVE/Hypothesis
The objective of this study was to examine sub-types of individuals with chronic fatigue syndrome based on variables that are associated with the energy envelope theory and to examine the role of coping strategies in explaining the differences found between the subtypes.

METHODS
Cluster analysis was used. Grouping variables included physical functioning, post-exertional malaise severity, and the extent to which an individual was outside of the energy envelope. These clusters were evaluated using discriminant function analysis to determine whether they could be differentiated based on coping styles.

RESULTS
Cluster analysis identified three groups. Clusters 1 and 2 were consistent with the energy envelope theory. However, Cluster 3 was characterized by patients with the most impairment, but they were to a lesser extent exceeding their energy envelope. Coping strategies explained a small percentage (10%) of the variance in differentiating the clusters.

DISCUSSION
Energy maintenance may be associated with improved functioning and less severe symptoms for some. However, patients in Cluster 3 were closer to remaining within their energy envelope and also used higher levels of adaptive coping but were more impaired than Cluster 2.

This suggests that adaptive coping strategies were not associated with improved health, as members of Cluster 3 were severely limited in functioning.

Examining the energy envelope and associated symptom patterns in chronic fatigue syndrome: does coping matter? by AA Brown, MA Evans, LA Jason in Chronic Illness,  12 April 2013

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Couples’ experiences of interacting with outside others in CFS

Abstract

OBJECTIVES

Social isolation and stigma are frequently reported by patients with chronic fatigue syndrome/myalgic encephalomyelitis and relationships in the home environment with those close to the patients (their ‘significant others’) may thus be particularly important. Rather little attention has yet been paid to the beliefs and experiences of ‘significant others’ themselves in this context. This study sought to explore in-depth the beliefs and experiences of both patients and ‘significant others’ in relation to chronic fatigue syndrome/myalgic encephalomyelitis.

METHODS

In-depth interviews using a semi-structured interview schedule designed around the core constructs of the Common-Sense Model of self-regulation were conducted with two patients with chronic fatigue syndrome/myalgic encephalomyelitis and their spouses. Interpretative Phenomenological Analysis was used to analyse interview data.

RESULTS

Experiences of social interactions in relation to chronic fatigue syndrome/myalgic encephalomyelitis with others outside of the relationship dyad emerged as a key issue for all participants when reflecting on their experiences of living with the condition. These concerns are presented under two themes: interactions with healthcare professionals and interactions with the social world.

CONCLUSIONS

It is evident that significant others play an important role in the lived experience of chronic fatigue syndrome/myalgic encephalomyelitis. For both patients and significant others, the wider social world and interactions with outside others may be important influences on dyadic coping in chronic fatigue syndrome/myalgic encephalomyelitis. Both future research and treatment interventions could usefully include a ‘significant other’ perspective.

Couples’ experiences of interacting with outside others in chronic fatigue syndrome: a qualitative study, by Joanna Brooks, Nigel King, Alison Wearden in Chronic Illness, e-pub ahead of print 12 April, 2013

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Distinguishing fatigue in different conditions

Abstract

CONTEXT: Unexplained fatigue states are prevalent, with uncertain diagnostic boundaries.

OBJECTIVE: Patients with fatigue-related illnesses were investigated by questionnaire and a novel semistructured interview to identify discriminatory features.

METHODS: Cross-sectional samples of women from specialist practices with chronic fatigue syndrome (n = 20), postcancer fatigue (PCF; n = 20), or major depression (n = 16) were recruited. Additionally, two longitudinal samples were studied: women with fatigue associated with acute infection who subsequently developed postinfective fatigue syndrome (n = 20) or recovered uneventfully (n = 21), and women undergoing adjuvant therapy for breast cancer experiencing treatment-related fatigue who subsequently developed PCF (n = 16) or recovered uneventfully (n = 16). Patients completed self-report questionnaires, and trained interviewers applied the Semi-structured Clinical Interview for Neurasthenia. The receiver operating characteristics curves of the interview were measured against clinician-designated diagnoses. Cluster analyses were performed to empirically partition participants by symptom characteristics.

RESULTS: The interview had good internal consistency (Cronbach α “fatigue” = .83), and diagnostic sensitivity and specificity for chronic fatigue syndrome (100% and 83%) and major depression (100% and 72%), with reasonable parameters for PCF (72% and 58%). Empirical clustering by “fatigue” or “neurocognitive difficulties” items allocated most patients to one group, whereas “mood disturbance” items correctly classified patients with depression only.

CONCLUSIONS: The Semi-structured Clinical Interview for Neurasthenia offers reliable diagnostic use in assessing fatigue-related conditions. The symptom domains of fatigue and neurocognitive difficulties are shared across medical and psychiatric boundaries, whereas symptoms of depression such as anhedonia are distinguishing.

Characterization of Fatigue States in Medicine and Psychiatry by Structured Interview, by BK Bennett in Psychosom Med. 2014 May 6. [Epub ahead of print]

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