An adrenalectomy mouse model reflecting clinical features for CFS

Posted on 02/06/2020 by wames

An adrenalectomy mouse model reflecting clinical features for Chronic Fatigue Syndrome, by  Jin-Seok Lee, Yoo-Jin Jeon, Samuel-Young Park and Chang-Gue Son in Biomolecules 2020, 10(1), 71; [https://doi.org/10.3390/biom10010071] (This article belongs to the Special Issue Inflammation as Target treatment for Chronic Diseases)

 

Research abstract:

Chronic fatigue syndrome (CFS) is one of the most intractable diseases and is characterized by severe central fatigue that impairs even daily activity. To date, the pathophysiological mechanisms are uncertain and no therapies exist. Therefore, a proper animal model reflecting the clinical features of CFS is urgently required.

We compared two CFS animal models most commonly used, by injection with lipopolysaccharide (LPS from Escherichia coli O111:B4) or polyinosinic: polycytidylic acid (poly I:C), along with bilateral adrenalectomy (ADX) as another possible model. Both LPS- and poly I:C-injected mice dominantly showed depressive behaviors, while ADX led to fatigue-like performances with high pain sensitivity.

In brain tissues, LPS injection notably activated microglia and the 5-hydroxytryptamine (HT)1A receptor in the prefrontal cortex and hippocampus. Poly I:C-injection also remarkably activated the 5-HT transporter and 5-HT1A receptor with a reduction in serotonin levels in the brain. ADX particularly activated astrocytes and transforming growth factor beta (TGF-β) 1 in all brain regions.

Our results revealed that LPS and poly I:C animal models approximate depressive disorder more closely than CFS. We suggest that ADX is a possible method for establishing a mouse model of CFS reflecting clinical features, especially in neuroendocrine system.

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Welsh Government proposes new advisory group for ME/CFS & pain

Posted on 02/06/2020 by wames

New Welsh Government Advisory Group for ME/CFS and pain

 

2014 Task & Finish Group Report

It is five years since the Welsh Government published a Task & Finish Report giving Health Boards an action plan for improving services for ME/CFS and Fibromyalgia.

WAMES has been a member of the national advisory group for the T&FG Report – the All Wales Implementation Group (AWIG) – which has met 4 times a year with representatives from Health Boards and government.

WAMES has also been actively challenging individual Health Boards to implement the recommendations, with little success. Health Boards have repeatedly ignored calls from patients and government to take ME service planning seriously.

New advisory group

The Welsh Government has now decided to take a different approach and merge three groups (Persistent Pain, Arthritis and ME/CFS and FM) into one advisory group. The aim will be to report to the Chief Medical Officer on issues the conditions share and bespoke issues relating to specific conditions. Established channels of communication will then be used to engage with Health Boards.

It is hoped the new group will be established by April 2020 and the new structure will be monitored for effectiveness after sufficient time has passed.

In addition Health Education and Improvement Wales (HEIW) will be in attendance at the new group so they understand the issues surrounding education, training and workforce development.

The Welsh Government research and development team – Health and Care Research Wales –  have confirmed funding is available for well designed research projects.

Patient representation

WAMES has questions about whether this new group will be more effective in enlisting Health Board commitment to providing care for people with ME than previous approaches, but we are pleased that the Welsh Government recognises the need to find a better way of working.

Kevin Francis, the Policy lead for ME in the Welsh Government is happy to meet with groups who support people living with ME, FM and pain conditions. He wishes to better understand the issues for those living with these conditions.  Please let Jan know if you wish to take up this offer. jan@wames.og.uk

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Conceptualising illness & disease: reflections on Sharpe & Greco

Posted on 02/06/2020 by wames

Conceptualising illness and disease: reflections on Sharpe and Greco (2019), by Carolyn Wilshire , Tony Ward in BMJ …Medical Humanities [Published Online First: 11 December 2019] doi: 10.1136/medhum-2019-011756

 

Article abstract:

In a recent paper, Sharpe and Greco suggest that chronic fatigue syndrome/myalgic encephalomyelitis (MECFS) can be viewed as an instance of “illness without disease”, and consequently, treatment should be directed towards altering the patient’s experience of, and response to, their symptoms.

We discuss two broad issues that arise from Sharpe and Greco’s article, one relating to the assumptions they make about MECFS and its treatment specifically, and the other relating to their conceptualisation of the illness/disease dichotomy. We argue that the term “illness without disease”, in the sense that Sharpe and Greco use it, is problematic because it can lead to unwarranted causal assumptions.

Following these critical comments, we present a new framework for conceptualising the relationship between explanatory disease models and the experience of illness.

Read full paper

Excerpt:

We have argued here that, in medicine, it is not appropriate to make claims about causation on the basis of non-specific observations, in which direction of causation has not been clearly established, or simply because there is a lack of anything better.17

Causal claims that are phrased at a psychological level of description need to be subjected to the same tests as any other causal claim.

Treatments founded on unsubstantiated claims—even psychological ones—can do harm, no matter how well intentioned they are.  Even if patients are not directly harmed by the treatment, they may bear other costs. For example, they may feel personally responsible if they fail to recover. Also, any concerns they do raise may be dismissed, or even caricatured.

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Cell danger response biology – the new science that connects environmental health with mitochondria & the rising tide of chronic illness

Posted on 02/04/2020 by wames

Perspective: Cell danger response biology the new science that connects environmental health with mitochondria and the rising tide of chronic illness, by Robert K Naviaux in Mitochondrion Vol 51, March 2020, Pages 40-45 [Available online 23 December 2019] https://doi.org/10.1016/j.mito.2019.12.005

 

Highlights

  • Mitochondria regulate the cell danger response (CDR) that controls innate immunity and healing.

  • Chemical pollutants in the environment lower the threshold for CDR activation.

  • Persistent activation of CDR inhibits healing and leads to chronic illness.

  • Metabolomics and exposomics can help guide new policies to lower the risk of chronic illness.

 

Research abstract:

This paper is written for non-specialists in mitochondrial biology to provide access to an important area of science that has broad implications for all people.

The cell danger response (CDR) is a universal response to environmental threat or injury. Once triggered, healing cannot be completed until the choreographed stages of the CDR are returned to an updated state of readiness. Although the CDR is a cellular response, it has the power to change human thought and behavior, child development, physical fitness and resilience, fertility, and the susceptibility of entire populations to disease.

Mitochondria regulate the CDR by monitoring and responding to the physical, chemical, and microbial conditions within and around the cell. In this way, mitochondria connect cellular health to environmental health.

Over 7,000 chemicals are now made or imported to the US for industrial, agricultural, and personal care use in amounts ranging from 25,000 to over 1 million pounds each year, and plastic waste now exceeds 83 billion pounds/year. This chemical load creates a rising tide of manmade pollutants in the oceans, air, water, and food chain. Fewer than 5% of these chemicals have been tested for developmental toxicity.

In the 1980s, 5–10% of children lived with a chronic illness. As of 2018, 40% of children, 50% of teens, 60% of adults under age 65, and 90% of adults over 65 live with a chronic illness. Several studies now report the presence of dozens to hundreds of manmade chemicals and pollutants in placenta, umbilical cord blood, and newborn blood spots.

Fig. 1. Chronic Health Disorders that have Increased 2-100 times since the 1980s

New methods in metabolomics and exposomics allow scientists to measure thousands of chemicals in blood, air, water, soil, and the food chain. Systematic measurements of environmental chemicals can now be correlated with annual and regional patterns of childhood illness. These data can be used to prepare a prioritized list of molecules for congressional action, ranked according to their impact on human health.

“When a deep injury is done to us, we never heal until we forgive.” -Nelson Mandela (1918-2013)

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Neuroinflammation, oxidative stress & neurogenesis in a mouse model of CFS, & the treatment with Kampo medicine

Posted on 02/03/2020 by wames

Neuroinflammation, oxidative stress, and neurogenesis in a mouse model of Chronic Fatigue Syndrome, and the treatment with Kampo medicine, by Qiang He, Mio Sawada, Naruhiro Yamasaki, Sumiyo Akazawa, Hisakazu Furuta, Hiroaki Uenishi, Xiangjin Meng, Takeshi Nakahashi, Yasuhito Ishigaki, Junji Moriya in Biological and Pharmaceutical Bulletin Vol 43 (2020) no. 1, pp 110-115 [DOI https://doi.org/10.1248/bpb.b19-00616]

 

Research abstract:

The diagnosis of chronic fatigue syndrome (CFS) is mainly symptom-based, and the etiology is still unclear. Here, we evaluated the pathological changes in the brain of a mouse model of CFS and studied the effects of Kampo medicine.

A mouse model of CFS was established through six repeated injections of Brucella abortus (BA) every two weeks for a period of 12 weeks. Neuroinflammation was measured by estimating interleukin (IL)-1β, IL-6, and interferon-gamma (IFN-γ), and oxidative stress by nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) 6 weeks after the last injection. Hippocampal neurogenesis was evaluated through Ki-67, doublecortin (DCX), and 5-bromodeoxyuridine (BrdU) assays.

The effects of Kampo medicines (Hochuekkito (TJ-41) and Hachimijiogan (TJ-7)) on neuroinflammation during CFS were studied. The wheel-running activity of mice was decreased by about 50% compared to baseline at 6 weeks after the last BA injection. The levels of IL-1β, IL-6, 3-NT, and 4-HNE were increased in both the cortex and the hippocampus of CFS mice at 6 weeks after the last BA injection. Hippocampal neurogenesis was unchanged in CFS mice. Treatment with TJ-41 and TJ-7 reduced the expressions of IL-1β, IL-6, and IFN-γ in the hippocampus but not in the cortex.

The results of the present study indicate that neuroinflammation and oxidative stress play important roles in the pathogenesis of CFS. The data further suggest that treatment with TJ-41 and TJ-7 could help reduce the inflammation associated with CFS in the hippocampus, but failed to improve the symptoms in CFS mice.

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Left out – a Norwegian documentary about ME & research

Posted on 02/02/2020 by wames

Left out – a documentary about ME

The documentary Left Out (De Bortgjemte) was shown on national TV in Norway in 2018 and now has its international release on YouTube with English subtitles, 29 January 2020.

Director Paul Schaathun followed some ME patients and Dr Oystein Fluge’s RituxME trial  for 2 years. The resulting film is both informative and touching.

When they realised she had ME they just let go of us. “Sorry, it’s ME, we can’t do any more. We had to fend for ourselves.                                  Anne Karen, Emile’s mother

Watch the film

 

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Comprehensive circulatory metabolomics in ME/CFS reveals disrupted metabolism of acyl lipids & steroids

Posted on 01/30/2020 by wames

Comprehensive circulatory metabolomics in ME/CFS reveals disrupted metabolism of acyl Lipids and steroids, by Arnaud Germain, Dinesh K Barupal, Susan M Levine and Maureen R Hanson in Metabolites 2020, 10(1), 34; 14 January 2020 [doi.org/10.3390/metabo10010034]

 

Research abstract:

The latest worldwide prevalence rate projects that over 65 million patients suffer from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), an illness with known effects on the functioning of the immune and nervous systems. We performed an extensive metabolomics analysis on the plasma of 52 female subjects, equally sampled between controls and ME/CFS patients, which delivered data for about 1750 blood compounds spanning 20 super-pathways, subdivided into 113 sub-pathways.

Statistical analysis combined with pathway enrichment analysis points to a few disrupted metabolic pathways containing many unexplored compounds. The most intriguing finding concerns acyl cholines, belonging to the fatty acid metabolism sub-pathway of lipids, for which all compounds are consistently reduced in two distinct ME/CFS patient cohorts.

We compiled the extremely limited knowledge about these compounds and regard them as promising in the quest to explain many of the ME/CFS symptoms. Another class of lipids with far-reaching activity on virtually all organ systems are steroids; androgenic, progestin, and corticosteroids are broadly reduced in our patient cohort.

We also report on lower dipeptides and elevated sphingolipids abundance in patients compared to controls. Disturbances in the metabolism of many of these molecules can be linked to the profound organ system symptoms endured by ME/CFS patients.

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Systematic review of randomized controlled trials for CFS/ME

Posted on 01/29/2020 by wames

Systematic review of randomized controlled trials for chronic fatigue syndrome/ myalgic encephalomyelitis (CFS/ME), by Do-Young Kim, Jin-Seok Lee, Samuel-Young Park, Soo-Jin Kim & Chang-Gue Son in Journal of Translational Medicine vol 18, no. 7 (2020)

 

Research abstract:

Background:
Although medical requirements are urgent, no effective intervention has been proven for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). To facilitate the development of new therapeutics, we systematically reviewed the randomized controlled trials (RCTs) for CFS/ME to date.

Methods:
RCTs targeting CFS/ME were surveyed using two electronic databases, PubMed and the Cochrane library, through April 2019. We included only RCTs that targeted fatigue-related symptoms, and we analyzed the data in terms of the characteristics of the participants, case definitions, primary measurements, and interventions with overall outcomes.

Results:
Among 513 potentially relevant articles, 55 RCTs met our inclusion criteria; these included 25 RCTs of 22 different pharmacological interventions, 28 RCTs of 18 non-pharmacological interventions and 2 RCTs of combined interventions. These studies accounted for a total of 6316 participants (1568 males and 4748 females, 5859 adults and 457 adolescents). CDC 1994 (Fukuda) criteria were mostly used for case definitions (42 RCTs, 76.4%), and the primary measurement tools included the Checklist Individual Strength (CIS, 36.4%) and the 36-item Short Form health survey (SF-36, 30.9%).

Eight interventions showed statistical significance: 3 pharmacological (Staphypan Berna, Poly(I):poly(C12U) and CoQ10 + NADH) and 5 non-pharmacological therapies (cognitive-behavior-therapy-related treatments, graded-exercise-related therapies, rehabilitation, acupuncture and abdominal tuina). However, there was no definitely effective intervention with coherence and reproducibility.

Conclusions:
This systematic review integrates the comprehensive features of previous RCTs for CFS/ME and reflects on their limitations and perspectives in the process of developing new interventions.

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The prevalence of pediatric ME/CFS in a community‑based sample

Posted on 01/28/2020 by wames

The prevalence of pediatric Myalgic Encephalomyelitis/Chronic Fatigue Syndrome  in a community‑based sample, by Leonard A Jason, Ben Z Katz, Madison Sunnquist, Chelsea Torres, Joseph Cotler & Shaun Bhatia in Child & Youth Care Forum, 23 January 2020 [doi.org/10.1007/s10566-019-09543-3]

 

Research abstract:

Background:
Most pediatric prevalence studies of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have been based upon data from tertiary care centers, a process known for systematic biases such as excluding youth of lower socioeconomic status and those less likely to have access to health care. In addition, most pediatric ME/CFS epidemiologic studies have not included a thorough medical and psychiatric examination. The purpose of this study was to determine the prevalence of pediatric ME/CFS from an ethnically and sociodemographically diverse community-based random sample.

Method:
A sample of 10,119 youth aged 5–17 from 5622 households in the Chicagoland area were screened. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for three selected case definitions. A probabilistic, multi-stage formula was used for final prevalence calculations.

Results:
The prevalence of pediatric ME/CFS was 0.75%, with a higher percentage being African American and Latino than Caucasian. Of the youth diagnosed with ME/CFS, less than 5% had been previously diagnosed with the illness.

Conclusions:
Many youth with the illness have not been previously diagnosed with ME/CFS. These findings point to the need for better ways to identify and diagnose youth with this illness.

Read full paper

Press release: Study finds many youth living with undiagnosed chronic fatigue syndrome

DePaul researchers unmask misunderstood chronic illness

Simon McGrath: Leonard Jason research finds that many young people have ME/CFS

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Health-related quality of life in patients with ME/CFS: an Australian cross-sectional study

Posted on 01/27/2020 by wames

Health-related quality of life in patients with myalgic encephalomyelitis/chronic fatigue syndrome: an Australian cross-sectional study, by N Eaton-Fitch, SC Johnston, P Zalewski, D Staines & S Marshall-Gradisnik in Quality of Life Research, 22 January 2020

 

Research abstract:

Background:
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and debilitating disorder associated with significant disruptions in daily life including. This study aimed to examine the impact of sociodemographic and patient symptom characteristics on health-related quality of life (HRQoL) of Australians with ME/CFS.

Methods:
Self-reported data collected from 480 individuals diagnosed with ME/CFS were obtained between August 2014 and August 2018. This cross-sectional survey analysed sociodemographic, symptom characteristics and HRQoL according to the 36-Item Health Survey (SF-36). Multivariate linear regression models were used to determine ME/CFS symptoms associated with eight domains of HRQoL.

Results:
Reported HRQoL was significantly impaired in ME/CFS patients across all domains compared with the general population. Scores were the lowest for physical role (4.11 ± 15.07) and energy/fatigue (13.54 ± 13.94). Associations with females, higher body mass index (BMI), employment status, cognitive difficulties, sensory disturbances and cardiovascular symptoms were observed in the physical functioning domain. Impaired pain domain scores were associated with high BMI, annual visits to their general practitioner, flu-like symptoms and fluctuations in body temperature. Reduced well-being scores were associated with smoking status, psychiatric comorbidity, cognitive difficulties, sleep disturbances and gastrointestinal difficulties.

Conclusion:
This study provides evidence that ME/CFS has a profound and negative impact on HRQoL in an Australian cohort.

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