Tuesday, December 8, 2015

10th Invest in ME International ME Conference Report

http://www.investinme.eu/IIMEC10.shtml#report
http://www.investinme.eu/Documents/IIMEC10/IIMEC10%20Conference%20Report.pdf

Invest in ME
PO Box 561, Eastleigh SO5O OGQ, Hampshire, UK
Telephone: 02380 251719 – 07759 349743
Web: www.investinme.org
Email: info@investinme.org

10th Invest in ME International ME Conference

INVEST IN ME – 10th International Conference
29th May 2015, London

Rosamund Vallings MB BS


I was privileged to attend the 10th Invest in ME conference in London
on 29th May 2015 following on from the 2-day colloquium attended by 60
invited delegates from around the world.

Participants from 17 countries were welcomed to the conference opening
by Invest in ME and the chair was then taken by Dr Ian Gibson.

The keynote speech was given by Professor Ian Charles (Norwich, UK).
He has recently been appointed by the Institute of Food Research to
lead the programme to develop the UK's new centre for Food and Health
based at Norwich Research Park. This is a large complex incorporating:
The Institute of Food Research, The University of East Anglia, the
Norfolk and Norwich University Hospital and the Genome Analysis
Centre. There will be interdisciplinary approaches to address many
complex problems.

He discussed the gut microbiome, explaining that we have ten times
more bacteria than cells. He asked the questions: "Do alterations in
intestinal barrier integrity and microbiota exist in ME?" and "Is
there evidence of immune exposure and reactivity to commensal microbes
in ME patients?" He will be working within an interdisciplinary model,
which will become an international hub for food and health research,
with top class scientists appointed. Many departments will be working
together.

This new approach will be holistic, systematic and integrated to
deliver faster innovation. It will be a site of excellence and will
liaise with government. The aim is to lead to personalized nutrition
to benefit the individual microbiome.

The first presentation was given by Mady Hornig (Columbia, USA). She
discussed markers of immunity and metabolism in ME. She described a
3-strikes hypothesis regarding development of the illness, involving
genes, environment and timing. These affect brain outcomes, and she
discussed the effects of the mother's own immune system on the
developing foetal brain. Her cytokine profile could be implicated in
the risks of the infant developing nervous system disorders, even
years later. The microbiome of the mother also influences the
offspring's immune system with potential risks. Many disorders of the
nervous system may stem from immune-mediated pathogenesis.

She then described how there is an increase in plasma levels of
pro-inflammatory cytokines associated with recent illness in ME, and
as the illness progresses, these levels fall. A striking finding is
the very high level of IFN-gamma in short duration illness. It is
possible that different cytokine profiles may affect the potential
benefit of different types of therapies. Therapies may need to be
different at different stages of the illness.

Looking at the cerebrospinal fluid (CSF) comparing ME, MS and
controls, there were some similarities between ME and MS but the
controls had very different immune signatures.
The patterns of immune
molecules in the CSF of ME subjects, who largely had been ill for many
years, were similar to those Invest in ME

Page 2 of 8

observed in Hornig et al.'s immune profiling studies using blood from
ME subjects of long-standing duration.

Discussing metabolomics, she then described 7 classes of 180
metabolites. Alterations were found in a wide range of metabolites in
ME, including ADMA, which is associated with nitrosative stress, and
in tryptophan and serotonin. These metabolomic changes were found to
be correlated with changes in cytokines.

In the gut, there may be imbalances due to foods leading to bacterial
fermentation. Probiotics and faecal transfers do have potential, as
have been found to prevent encephalopathy in cirrhosis of the liver.

A question was asked as to whether the effects of SSRIs may be
affected by the serotonin levels and whether the duration of the
illness could be implicated here. It may be that patients will need to
be categorized according to illness duration, and there may be a
subgroup who will respond. But serotonin levels are not the only
mechanism. It is likely to be more complex than that.

Jonas Berquist (Uppsala, Sweden) describing himself as an analytical
chemist, discussed the Proteomics in ME/CFS. The first ever analytical
chemist was Tobern Olaf Bergman from Sweden. So there is a strong
Swedish tradition in this field. Berquist's lab does general research
and uses mass spectrometry looking at endogenous analytes. He
described proteomics as life's molecular machines – i.e. proteins
which carry out all functions of the body.

He looked at when, where, how proteins are expressed.
Post-translational modifications (PTMs) occur. This can be measured
using 3D gel electrophoresis, but nowadays "shotgun" proteomics is
used to separate them out. Many instruments are used and some of them
are very big machines, using high resolution mass spectrometry. It is
important to use the correct samples from serum and tissues. The tests
are extremely sensitive. He compared the small concentrations
measurable with these techniques as the amount found if a cup of
coffee is poured into a swimming pool.

When looking at the CSF, the total volume is about 150ml and 5-600ml
daily is produced. Sample handling needs to be extremely careful. His
labs have produced a 776 page list of the peptides in the CSF. There
are different ranges with overlaps in different conditions. The study
gives meaningful insights into the biological processes in ME/CFS.
There are significantly changed proteins involved in neurologic,
metabolic and immune diseases. He has looked at upstream and
downstream analysis.

The conclusion is that this work could lead to biomarkers, which maybe
diagnostic, prognostic and therapeutic.

Luis Nacul (London, UK) reviewed the epidemiological evidence on
ME/CFS looking at the current status and implications for research and
service delivery. He described it as a jigsaw coming together. He felt
that the symptoms of encephalitis were very similar to the symptoms of
ME, which MAY therefore BE indicative of neuro-inflammation. He said
that the diagnosis of ME SHOULD BE DISTINGUISHED FROM THAT OF Chronic
Fatigue Syndrome, AS usually the term ME was indicative of more
symptoms. He mentioned a variance in prevalence rates, with females
more commonly affected than males. Overall population estimates are
between 0.1% and 0.7%. Young adulthood is the commonest age of
incidence. In patients with ME/CFS, activity is significantly
diminished. He stressed that we need to look at specificity and
sensitivity, and risk ratio and risk difference. Specificity should
take precedence over sensitivity for validity.

The NICE guidelines ON MANAGEMENT were mentioned. There are LIMITED
effects shown in the clinical response to CBT. But the results may not
be valid as STUDIES USED IN THE META- ANALYSES ARE OF POOR QUALITY AND
A LARGE PROPORTION patients DID not complete a trial, and therefore
results may not be valid. It could be described as an additional
"coping" therapy, WHICH SHOULD NOT DISTRACT US FROM FINDING SPECIFIC
TREATMENTS FOR ME. Invest in ME

Page 3 of 8

We need to concentrate on biomarkers for the future, with case
stratification and intervention strategies. The current UK biobank has
500 participants, with 17,000 aliquots stored as of March 2015.

Amolak Bansal (Surrey, UK) gave an overview of the diagnosis and
differential diagnosis on ME. He explained how fatigue occurs in many
illnesses, but is the cardinal feature of ME/CFS. He said the
post-exertional malaise is hard to explain. He then went through the
various criteria being used to diagnose the illness. He discussed the
differences between the criteria (CDC, ICC etc.). He thinks that the
term SEID may be too simple. He talked of exclusion criteria,
including temporary exclusion criteria, such as hypothyroidism and
morbid obesity leading to sleep apnoea; and psychiatric exclusion
criteria. He mentioned comparisons which are made between the terms
CFS and ME.

He then went through the Sutton scoring system developed at his
clinic. The main symptoms have a "loaded" score: e.g. PEM scores 3
points, sleep problems 2 and all other symptoms 1 point. 8 or more
points out of 13 points is needed for a diagnosis. All patients must
have post exertional malaise. For subjects involved in research he
uses a score of 10+ from 13 to ensure a critically well-defined
population. Subjects with a significant depression or anxiety are
excluded from research but can still be diagnosed with ME/CFS for
management purposes if they have sufficient points and the depression
and anxiety is secondary to the ME/CFS. Treating the depression,
anxiety and ME/CFS are all critical to improvement in these people. It
is important to note that sensitivity to medication, and alcohol
intolerance are very common in ME/CFS. Fewer than 10% patients can
tolerate alcohol. Another unusual sign in 60 % patients is altered
pupillary reflexes (alternating dilatation and contraction while a
light is shined) and sighing respirations. Other physical signs
include: joint hypermobility (20%), increased respiratory rate (80%),
coldness of peripheries (70%). Conditions that can cause symptoms
similar to ME/CFS include: hypothyroidism, Addison's disease,
pituitary dysfunction, Sjogren's syndrome, gluten sensitivity,
persistent anxiety, primary sleep disorder, Ehlers Danlos Syndrome
joint/hypermobility type, cardiac dysfunction, Parkinson's disease and
temporo-mandibular joint disorder.

He then compared ME/CFS with depression and anxiety. The sleep
disturbance in ME/CFS is different to that in depression and the
former are also markedly hypersensitive to psychoactive medications.
Functionally those with ME/CFS can start a task, but then trend
downwards while those with depression cannot start a task as they have
reduced motivation, but once started they can often manage to complete
it. Those with ME/CFS rarely resort to alcohol, while those with
depression do frequently.
However chronic anxiety associated with
ME/CFS will deplete energy further, contribute to faintness, cognitive
difficulties and increased respiration.

He then talked about appropriate investigations. The basic blood
workup should be done as for all fatiguing illnesses and these are
sufficient to exclude other causes for chronic fatigue in the majority
of patients. Things to add in depending on history and symptoms may
be: ANA, CK, calcium, magnesium, tests for Addisons and on rare
occasions infection serology (Lyme, viral) and neurological
abnormalities (MRI, fMRI, PET scans). Other tests that are
occasionally considered include tilt table, ECG monitoring and
neuropsychological tests. Unfortunately in the UK searching for
triggering infections, such as viral, bacterial (incl spirochaetes),
protozoa and fungi (no evidence for involvement of candida) is rarely
rewarding in terms of offering specific therapeutic options. History
of immunisations on rare occasions may suggest a possible trigger and
there is recent controversy about the HPV vaccine.

Quite often it is a difficult question of how far to delve into issues
such as life events, stress, physical injuries, environmental toxins
and childhood trauma as there is at least some evidence that they may
all play a cofactor role in precipitating ME/CFS. He then discussed
the importance of the control population in ongoing ME/CFS Invest in
ME

Page 4 of 8

research. Although the ideal control group would be family members
this is often difficult and perhaps monitoring people with ME/CFS
through several periods of relapse and remission would be best way
forward.

Sonya Marshall-Gradisnik and Don Staines (Griffith University, Gold
Coast, Australia) presented their work on biomarkers in ME/CFS. They
had had two recent papers published –

http://www.la-press.com/examination-of-single-nucleotide-polymorphisms-snps-in-transient-recep-article-a4824

and

http://www.la-press.com/examination-of-single-nucleotide-polymorphisms-in-acetylcholine-recept-article-a4862

The two researchers highlighted these papers are from a series of
papers that will be released in the coming months.

These two papers discussed this important work on single nucleotide
polymorphisms (SNPs) in both transient receptor potential (TRP) ion
channel genes and acetylcholine (AChR) receptor genes. TRP and AChR
are part of the ancient or innate immune system. The TRP ion channels
respond to environmental threats, temperature, chemicals etc. They are
distributed throughout virtually all cells of the body. The range of
threats may lead to widespread symptoms. Imposed physical activity is
the wrong thing to be doing as it will likely exacerbate adverse
signaling in patients expressing these SNPs.

Acetyl choline is a major neurotransmitter seen throughout the entire
peripheral, autonomic and central nervous systems and is also part of
the non-neuronal signaling mechanisms of the ancient immune system.

SNPs may cause change in protein structure of translated protein and
therefore possibly change in function of these ion channels or
receptors.

280 people were recruited and screened using the CDC criteria and
exclusion criteria. 115 had ME/CFS, 90 were non-fatigued and 75 were
excluded. Those included were given questionnaires (SF36, FSS, KPS),
and included housebound patients. Bloods were taken for testing.

13 SNPs were associated with ME/CFS compared to controls (9 – TRPM3, 2
– TRPA1, 2 – TRPC4). TRPA1 is activated by exogenous and endogenous
inflammatory agents, leading to pain and inflammation.

It regulates neuropeptides and is a multiple chemical receptor. It is
associated with changes in neuropeptide receptors and inflammatory
cytokine profiles. TRPM3 is located on the pancreaticβ cells and in
the CNS. It is associated with pain. TRPC4 is associated with
vasomotor function and smooth muscle function.

17 SNPs were associated significantly with AChRs in ME/CFS patients (9
– mAChM3, 5 - nACh alpha 10, 1 -AChR alpha 5 and 1 - nAChR alpha 2

Collectively, AChR and TRP SNPs likely influence the gastrointestinal
tract involving insulin and glycogen secretion, B and T lymphocyte
development and proliferation, and neurological systems associated
with sleep, pain and arousal.

This research highlighted the possible role of TRP ion channels and
AChRs in the onset of ME/CFS.

Next Generation: A panel discussion then ensued involving 4 new
student researchers, and it was good to hear their involvement, which
bodes well for the future. The students were - Invest in ME

Page 5 of 8


- Bharat Harbham (UEA/IFR
- Fane Mensah (UCL
- Navena Navaneetharaja (UEA/IFR
- Daniel Vipond (IFR)

Jo Cambridge (London, UK) then talked about B cell biology and ME/CFS.
She gave some background history explaining that Rituximab had been
used in 1998 to treat Rheumatoid Arthritis and SLE. The work of Mella
and Fluge then further drove the hypothesis that B cell depletion
could be implicated in ME/CFS. Her group looked at B Cell biology,
biomarkers for response and relapse and other B cell directed
therapies. The B cell has a large number of markers. Markers tell the
age of the cell and other expressions. Every new B cell has a
different receptor. Adherence is involved. B cells move through plasma
cells to make antibodies. Antibodies are a form of B cell receptor,
and are released onto surfaces, and bind to help clear macrophages
from the body. They are made in the bone marrow and circulate to
lymphoid organs. Antibodies recognize the different stages on the
target bug. (e.g. antigen). IgM, IgA, IgG are all a different shape,
all recognize the same antigen, but bind to cells in different ways.
In a normal immune response, IgM is apparent in the first 7-10 days,
then IgG. Memory B cells also form to attack recurrent bugs. There is
interaction with T cells causing cytokines to help B cells make the
antigen.

Cytokines interleukin8 and interleukin5 are elevated in ME/CFS and
interleukin23 is down. There are also early and late effects in this
illness leading to different cytokine levels. Antibodies in disease
can form to "self" giving rise to immune complexes lodging in tissues
leading to inflammation (e.g. lupus, rheumatoid arthritis). The
antibodies bind and damage or change cell function. They can interfere
with communication between cells.

Rituximab works in diseases where there are antibodies, leading to B
cell depletion by recognising CD20 on the B cell. This in turn leads
to B cell destruction in the circulation. B cells can regenerate.
Changes occur in levels of Anti CCP after a single rituximab course.
It is very complicated.

In ME/CFS there were positive results from use of rituximab in Norway.
Patients do differ and there is no clear picture of the B cells. The B
cell phenotype can be compared to the ME/CFS demographics using flow
cytometry. One can look at complex things such as maturation, plasma
cells, percentage of B cells in the blood, associated demographics,
percentages of memory and naïve B cells etc.

CD24 is present on B cells associated with maturation (mainly on young
cells). CD38-CD21 – memory B cell subsets – high expression in
controls, less so in ME/CFS. Duration of illness gives different
levels, with B cells normalizing over time. There are no differences
in classical B cells.

Immune brain communication and relationship to inflammation induced
fatigue were discussed by Neil Harrison (Sussex, UK). He outlined the
symptoms associated with sickness behavior and listed the behavioural
changes that occur to protect the body. He explained how cytokines
injected into rodents led to symptoms of sickness behavior. Humans
given high doses of interferon-αto treat Hepatitis C also develop
sickness behavior and often experience severe fatigue. There is
immune-brain communication via a number of pathways, and in particular
via the vagus nerve. The microglia are also activated leading to brain
inflammation.

Typhoid vaccine was used as a bacterial mimic. The fMRI showed
activity++, and PET showed increased metabolism particularly within
immune-brain communication pathways. Inflammation induced insular
activity, which predicts fatigue. Interferon mediated fatigue is a
side effect of interferon-αtherapy (a viral mimic). MRI scans were
done before, and shortly after beginning Interferon-alpha therapy then
patients followed up for their 6-month duration of treatment. A
challenge with IFN lead to the onset of fatigue and Invest in ME

Page 6 of 8

MRI changes within 3 hours. One could also use changes observed on MRI
to predict which patients would subsequently develop the worst fatigue
during their 24 weeks of treatment. There are implications for
post-IFN fatigue and post viral fatigue. He asked the question "Do
structural brain abnormalities persist post-inflammatory challenge?".

John Chia (California, USA) updated us on his work with enteroviruses.
He explained that there are many illnesses associated with
enteroviruses. Most doctors are not trained to diagnose enterovirus
infection. They are difficult to recognize. In 1995 41% CFS patients
had positive serum enterovirus. He presented his research up to the
present. He worked initially with blood samples, but moved onto tissue
samples. In patients with persistent gastrointestinal symptoms, there
was no evidence of H Pylori. But there were positive abdominal tender
points, and focal gastritis on endoscopy (often mild).135 out of 165
patients were positive for VPI within the parietal cells, compared to
7 out of 34 controls. He tried to culture the viruses, but none
survived. In 2008, viruses were found in biopsies (Enterovirus capsid
protein) 81% showed VPI and 91% dRNA. Work with SCID mice showed
effects of enterovirus infection after injection. (66% positive
compared to 10% controls). He says that initial infection in the
stomach is not controlled by the immune response. Enteroviruses travel
via the vagus to the brainstem.

Claire Hutchinson (Leicester, UK) had looked at visual processing in
ME. She talked about how visual symptoms were commonly reported in the
63 patients studied, using questionnaires and free report of symptoms.
She wanted to map anomalous visual behavior onto the visual pathway,
and to provide evidence to support symptom reports. There was
experimental for the existence of visual stress/pattern glare in 20
patients compared to controls, which may reflect cortical
hyperexcitability. In a study looking at visual attention and the
ability to ignore background information (29 patients, 29 controls),
found basic visual processing speed was normal, but both divided
attention and selective attention were slow. She also presented data
showing that, under some conditions, eye movements are less accurate
in people with ME.

Betsy Keller (Ithaca,USA) went through activity guidelines to avoid
symptom flares. This was an active talk incorporating audience
participation. She talked about energy currency and post-exertional
malaise (PEM), describing short term anaerobic, long term anaerobic
and aerobic stages (>2 minutes) - the latter not being suitable for a
person with ME/CFS because this energy system fails to recover
normally. She described the abnormal recovery response, with ME/CFS
patients taking 3 days or longer to recover from 5-10 minutes on a
treadmill. PEM is the defining quality of this illness. It is easier
to avoid it than to recover from it. Her advice is to pre-empt PEM
with scheduled rest periods, do not wait for a crash, pace carefully,
know your triggers and avoid or minimize them. Exercise should be
redefined with focus on quality of life and use of the short-term
energy systems that do work. Yoga and Tai Chi are suitable forms of
exercise. The strategy for physical activity should use functional
movement that is restorative, with a goal to improve. Aim should be to
use the anaerobic energy systems with a work/rest ratio of 1:3, 1:4 or
more if needed. That is, 'work' for 30 seconds, recover for 90 seconds
(1:3).

She went on to explain the importance of core stability to conserve
energy. The core includes muscles, bones, connective tissue of the
trunk from the neck to hips- it connects the extremities. She
explained the weight of the head and how it increases if one slouches
(using extra energy unnecessarily). Warm up should begin with focused,
square or nose-breathing (4 sec inhale, 6-8 exhale). This will often
help symptoms too by better oxygenating the tissues.

5 steps to align core: 1) Contract pelvic floor (contract muscles that
stop flow of urine or Kegel), 2) draw in umbilicus (draw belly button
toward spine), 3) raise ribcage (rib cage points up toward ceiling or
umbrella diaphragm). 4) Lift shoulders up to ears then back and let
drop down, 5) retract chin. (Some of these exercises can be done lying
down). Back extension is important (lying on floor on belly). She then
ran through some exercises on the floor or Swiss ball straightening
arms and legs - alternate and opposite sides. These exercises
strengthen the core. It is important to assess how one feels the next
day to determine if the work/rest ratio is sufficient. If structured
activity works, core stability improves, movement Invest in ME

Page 7 of 8

becomes more efficient and less energy draining. Activities need to be
monitored and modified. The exercises should be very brief e.g. 30
seconds of activity, 90 seconds of rest, 3 times. The heart rate (HR)
can be monitored and should not exceed the anaerobic threshold, and
watch to see which exercises work at what HR. There is a perceived
exertion scale and the aim should be to stay at the bottom level.

She described structured activity as empowering, improving quality of
life, giving a sense of control and being off the rollercoaster.
Energy conservation involves pacing, body position, joint protection
and activity planning. There is need to think circularly not linearly
(use a work/rest ratio all day), acknowledge limitations, aim for core
stability and structure physical activity. She then outlined 10 simple
energy-saving tips shared with her by Staci Stevens of the Workwell
Foundation:

Make bed while you are in it or not at all
Take things around the house in a back pack.
Shower sitting down
Simplify clothes and hair
Use an answering machine
Pack groceries smartly ready for unpacking
Cook ahead
Get disabled car park
Prioritize chores
Learn to say No and Yes

Olav Mella (Bergen, Norway) brought us up to date discussing the Phase
2 and 3 studies of the rituximab trial. The Phase 2 study will be
published shortly. 20% patients had a transient worsening of symptoms.
There was marked improvement of physical function in 6 of 9 previous
placebo patients. Half of the original responders were still
responding at the end of follow up (36 months). The quality of life of
the responders was very good. Only 5 patients were as low as 30%.
During the trial levels of function were tested using a bicycle on a
ramp. Experience with measuring endothelial dysfunction was gained.
Maintenance therapy may sustain response

A new study is now underway. Patients recruited have been ill for 2-15
years. The Canadian criteria were used for diagnosis. 4 university
hospitals and a community hospital were involved. Patients were given
information and filled in the De Paul questionnaire. Biobank material
was withdrawn and frozen. Patients undergoing the ramp test may need
to wait 3 months before start of treatment to get back to their normal
level. The study is randomized, double blinded, placebo-controlled.
Study period will be 24 months, so results will be available in summer
2017, unless there are serious side effects. There will be no access
to randomisation. All monitoring will be external. The physicians
concerned will not see the patients. Rituximab 500mg/m2 will be given
on days 0 and 15, and then 500mg at 3, 6, 9 and 12 months. Patients
will monitor themselves. SF36 will be used every 3 months and FSS at
zero, 6, 12, 18 and 24 months. Electronic activity will be assessed at
zero and 18 months, using a wrist band. Blood samples will be drawn
regularly for biobank freezing.

The primary endpoint will be the level of fatigue over 24 months. The
secondary endpoint will be changes in QOL, and any effects of
toxicity.

Sub-studies will include endothelial dysfunction (large vessels -
ultrasound and microvessels - PORH analysis) – Is there correlation
between endothelial dysfunction and ME and improvement parallel to
endothelial dysfunction? Ergo spirometry can be used, if patient is
able, to see if there are changes in the anaerobic threshold.

Another sub-study will look at gastro-intestinal function. Invest in ME

Page 8 of 8

These are high quality studies hoping for good clinical response. One
must expect up to 20% placebo response, and hope for a 50% rituximab
response. One needs to look at clinical characteristics of the
responders. There may be a 4-5 month delayed response. The biobank
will be useful. There may be political impact. Another multicenter
trial elsewhere is needed. Toxicity also needs to be considered. Some
patients cannot tolerate the treatment.

A further new study using cyclophosphamide started in March 2015. This
is a cheaper immune-modulating drug. It shows major improvement in
treatment for breast cancer. 40 ME patients have been recruited with 6
infusions to be given every 4 weeks. There are 3 groups of patients:
those not treated with rituximab, previous non-responders to rituximab
and those who have recurred after rituximab. Patients with mild to
moderate illness are recruited and the trial will last 2 years. It
does not include young patients or those at risk of pregnancy. It will
be tried later on for 20 more severe patients.

The conference concluded with thanks to all speakers and closing
remarks from Dr Ian Gibson and Invest in ME, and all agreed it had
been the very best yet.

I would like to thank Invest in ME and ANZMES for making it possible
for me to attend this excellent event.

Rosamund Vallings MNZM, MBBS

www.investinme.org

              ---------------------------------------------
                Send posts to CO-CURE@listserv.nodak.edu
             Unsubscribe at http://www.co-cure.org/unsub.htm
    Co-Cure Archives: http://listserv.nodak.edu/archives/co-cure.html
              ---------------------------------------------
Co-Cure's purpose is to provide information from across the spectrum of
opinion concerning medical, research and political aspects of ME/CFS and/or

FMS. We take no position on the validity of any specific scientific or
political opinion expressed in Co-Cure posts, and we urge readers to
research the various opinions available before assuming any one
interpretation is definitive. The Co-Cure website <www.co-cure.org> has a
link to our complete archive of posts as well as articles of central
importance to the issues of our community.
              ---------------------------------------------

No comments: