I believe that a discussion of the cytokines related to the “cytokine storm” might prove useful.
In the post by anon_22 about the anti-avian influenza meeting she attended in Paris, there was an article discussed (PMID 15148370, thanks for posting it fredness!) which stated that there was an elevation in the cytokines TNF-alpha and induced protein 10 (IP10) in H5N1 patients.
Briefly, TNF-alpha is produced by a number of cells, notably T-cells and macrophages (T-cells being the immune cells which target infected cells of a specific type, in our discussion, cells which are infected by H5N1. Macrophages are involved in engulfing bacteria and other pathogens and cellular debris and aid in initiating T and B cell responses by “presenting” antigenic portions of pathogens to these immune cells, resulting in activation of T and B cells which “recognize” the antigens. It is a MUCH more complex process than I have just described, involving T-helper cells, other cytokines, etc.) Cells will produce TNF-alpha in response to viral or bacterial products, multiple cytokines (interleukins, etc.) and other stimuli. TNF-alpha will cause pro-inflammatory events including increased “stickiness” of vascular endothelium to increase neutrophil entry into the surrounding tissue (neutrophils are cells which are rapidly mobilized from the blood stream and can destroy invading pathogens early on). TNF-alpha can also destroy some pathogens directly and acts to increase production of other inflammatory cytokines. TNF-alpha will also help to initiate cell death in virally-infected cells (see below). Although I have not read them yet, the following review articles appear to give a promising introduction to this particular cytokine:
Review of TNF-alpha and viral pathogenesis (PMID 10719836) Review of modulation of TNF by microbial pathogens (PMID 16518473) Review of TNF receptors in cell death and antiviral responses (PMID 14532286)
I know little about IP10, but what I could glean from PubMed was the following: IP10 Is a T-cell chemoattractant. They also appear to stimulate T-helper cells which activate effector T-cells and B-cells (B-cells give rise to antibody-producing plasma cells). IP10 also appears to initiate apoptosis (a programmed sequence of events whereby a cell will commit suicide) in virally-infected cells (in this case Tet-On/HeLa cells infected with coxsakievirus B3) via a p53-mediated apoptotic pathway (PMID 15988033)
Other papers of interest note that there was an increase in IP10 in pediatric SARS patients (PMID 15781938) and that mast cells (causing much of the inflammatory response in asthma patients) will migrate to airway smooth muscle in culture in response to IP10 (PMID 15879427), perhaps having implications for other respiratory illnesses. One paper (PMID 16314440) lists neuronal precursor cells as constitutively (constantly) producing TNF-alpha receptors, which, when activated by TNF-alpha, result in production of IP10 via a p38 MAP kinase signaling pathway. IP10 production is also stimulated in various tissues by interferon-gamma and vascular endothelial growth factor. These findings imply that multiple cell types are capable of increasing IP10 levels directly or indirectly, with IP10 perhaps also regulated by TNF-alpha. TNF-alpha was also capable of inducing apoptosis in these neuronal precursor cells, so that multiple pathways leading to cell injury appear possible with these 2 cytokines.
Thanks to anon_22 and fredness for getting the ball rolling. Sorry about not being able to link to the articles. You should be able to access many of them via PubMed.
If you haven’t died of boredom from the above, anybody want to discuss cytokines??
The most important thing about cytokines IMHO is that statins appear to down-regulate them and so could be a good alternative to antivirals since most of the world would not have them. See this discussion for more details.
Off for breakfast and hit the coffee.
Statins “might be the only agents that could alter the course of a global pandemic”
Pandemic Influenza: A Potential Role for Statins in Treatment and Prophylaxis
Statins or any other single-point solution are only Wishful Thinking.
Its probably a less damaging option than steroids, but just as dyregulating as the cytokinic dysregulation that its attempting to correct.
You can’t really steer a boat if you can’t find the rudder. We don’t know where the rudder is right now on this boat.
Pursuing something like TNF-Alpha down-regulation is almost like pursuing THE provocative white mouse in a room of 800 white mice and 12 black. The TNF-alpha, its precursors, predecessors and upstream agents are widely featured throughout the body for much more than just viral attack.
We’re playing with fire again.
NS1.
The thing about statins is that they are not dangerous, like steroids.
And they are cheap, not like tamiflu.
And they are available, as generics, so potentially many millions can benefit.
I don’t think it is playing with fire to suggest we should take a closer look at statins as possible mitigation.
And in this context, because of its availability and low cost,neven if we are talking about a small improvement in survival, it has the potential to translate into millions of lives saved.
So, is it not fair to say that the C-storm is a bad thing and young donors are losing their lives at an alarming rate?
Mitigation is key and a look at recovered cases deserves greater inquiry as well.
Also, Is it fair to say that the “healthy immune system” is causing an increased infection rate?
To clarify…to say that the C-storm is a bad thing…
Or at the very least seems to be in this case.
How do you inhibit/alter/cease the natural course of a cytokine producing agent and just what is that?
Are there not TNF-A inhibitors on the market? (Imfliximab, etc.)? Monoclonal antibodies?
Good Questions, Mr White42 and Sarge. The problem is one of unintended consequences. The flaw with many experiments and treatments is that in stopping one thing, you oftentimes tigeer another which can give rise to even more problems. On the statin thread, I pointed to an article which shows that certain statins can increase INF-gamma production by T cells. INF-gamma is what triggers production of IP10, discussed above. Thus even the good have bad associated with them. Sarge, TNF stands for tumor necrosis factor, a substance which has a HUGE number of activities including helping to prevent tumor growth. You would have to knock-out the bad (cytokine storm) but keep the good (anti-tumor effects) and that COULD be done with a better understanding of cytokine interactions and especially of cytokine regulators. That is why I thought this thread might be useful to discuss options (such as the monoclonals you brought up) and what is known that could lead us down a good path or a bad one. I am gravely worried as NS1 point out that there may be too many unknowns, leading again to unintended consequences, but with H5N1 knocking at our door, I think we had better examine what we do know and hope we can find something to light our way. With luck, (as anon_22 hopes for statins)it will do more good than harm.
That should have read “trigger”…unintended consequences…
Gram-Positive Cell Walls: Teichoic Acids and Glycopeptide Cell Wall Fragments from Peptidoglycan Preview from Unit-1 http://tinyurl.com/r5bjb
In order to protect against infection, one of the things the body must initially do is detect the presence of microorganisms. The body does this by recognizing molecules unique to microorganisms that are not associated with human cells. These unique molecules are called pathogen-associated molecular patterns. Molecules unique to gram-positive cell walls, such as peptidoglycan monomers and teichoic acids, bind to pattern-recognition receptors on a variety of defense cells of the body causing them to synthesize and secrete a variety of proteins called cytokines. These cytokines can, in turn promote innate immune defenses such as inflammation, phagocytosis, activation of the complement pathways, and activation of the coagulation pathway.
Thalidomide-based TNF- inhibitors for neurodegenerative diseases
CYTOKINES:A wide variety of intercellular regulatory proteins produced by many different cells in the body which ultimately control every aspect of body defense. Cytokines activate and deactivate phagocytes and immune defense cells, increase or decrease the functions of the different immune defense cells, and promote or inhibit a variety of nonspecific body defenses.
Promote Or Inhibit. Okay, can we focus the response?
Can we regulate the regulator?
Can one artificially lower/raise the temp. of a patient and slow/control the cytokine response? Has anything been done for any other ailments to adjust the response?
An interferon—related cytokine storm in SARS patients http://tinyurl.com/rmeph Abstract:
Fourteen cytokines or chemokines were analyzed on 88 RT-PCR-confirmed severe acute respiratory syndrome (SARS) patients. IFN-, IL-18, TGF-, IL-6, IP-10, MCP-1, MIG, and IL-8, but not of TNF-, IL-2, IL-4, IL-10, IL-13, or TNFRI, were highly elevated in the acute phase sera of Taiwan SARS patients. IFN- was significantly higher in the Ab(+) group than in the Ab(-) group. IFN-, IL-18, MCP-1, MIG, and IP-10 were already elevated at early days post fever onset. Furthermore, levels of IL-18, IP-10, MIG, and MCP-1 were significantly higher in the death group than in the survival group. For the survival group, IFN- and MCP-1 were inversely associated with circulating lymphocytes count and monocytes count, but positively associated with circulating neutrophils count.
It is concluded that an interferon—related cytokine storm was induced post SARS coronavirus infection, and this cytokine storm might be involved in the immunopathological damage in SARS patients.
You can pick up more info as well as this at http://tinyurl.com/m38jl
<snip> The complex replication cycle for orthopoxviruses, and the pivotal role for viralspecific immunomodulatory proteins which contribute to escape from immunologic surveillance, provide many unique targets for therapeutic intervention. The “toxemia” of smallpox has been elucidated in part by variola-infected primate studies which revealed the central role of apoptosis and the evolution of a cytokine storm leading to hemorrhagic diathesis, resembling fulminent “black” smallpox.
From : Countermeasures to the Bioterrorist Threat of Smallpox http://tinyurl.com/g46d2
Me earlier;-/ Mr White42 – at 00:25 Can one artificially[or are there any means by which temp is major factor-,yes.] lower/raise the temp. of a patient and slow/control the cytokine response? Has anything been done for any other ailments to adjust the response?
Little is known about the effects of brain death on cytokine expression in peripheral solid organs. It has been suggested that organs experiencing warm ischemia resulting from hemodynamic deterioration of the brain-dead donor, followed by cold ischemia during storage, express higher levels of cytokines than those from ideal living donors.
Examination of the presence of soluble cytokines (interleukin [IL*]−1â, tumor necrosis factor [TNF]-á, and IL-6) in the circulation of brain-dead patients showed increased IL-6 levels only (47); up-regulation of transcriptional levels of TNF-á and IL-6 have been reported in association with episodes of transient focal cerebral ischemia (48). http://tinyurl.com/nzspb
Not to leave any “stone” unturned, marijuana is a powerful, cheap and ubiquitous immunomodulator, with mixed but primarily anti-inflammatory effects:
FROM Nature Reviews Immunology 5, 400–411 (2005); doi:10.1038/nri1602 Cannabinoids bias the immune response away from T helper 1 (TH1)-cell responses, by mechanisms that involve cannabinoid receptors. It is possible that signalling through these receptors, expressed by T cells, B cells or antigen-presenting cells, suppresses the expression of TH1-cell-promoting cytokines and increases the expression of TH2-cell-promoting cytokines
There are numerous reviews of the immunomodulatory effects of marijuana (often via cannabinoids, i.e. parts of the plant other than the psychoactive CB receptor agonist THC. It might be useful to discuss this in the context of cytokine storm mitigation.
“stone” unturned… Good one. Please provide a light, ahh, a link, D-soup.
also:Transcriptional and translational regulation of heat shock proteins in leukocytes of endurance runners Heat shock proteins (HSP) represent cell-protective and antioxidant systems that may be induced by reactive oxygen species, cytokines, and hyperthermia. In the present study, we evaluated the influence of heavy endurance exercise and training on HSP27 and HSP70 in peripheral leukocytes of 12 athletes (before and at 0, 3, and 24 h after a half-marathon) and 12 untrained controls on protein and mRNA levels by flow cytometry and RT/PCR, respectively. HSP transcripts increased significantly immediately after acute exertion accompanied by elevated levels of corresponding proteins. http://jap.physiology.org/cgi/content/full/89/2/704
Many Cats – at 23:27
Exactly, if we down-regulate TNF-alpha, then we will likely down-regulate the interferon response (already a target of H5N1). With no first level immune response from the interferon pathway and no commensuerate replication speed reduction, you will be looking at a patient with widespread lysis, rapid onset viremia and little to no immune response.
Remember, we are talking about H5N1 or another pandemic strain, novel and unknown to our systems, no immune memory, no immediate antibody-mediated response.
Try to managing TNF-alpha and you’re cutting the 911 emergency phone lines and emplacing barricades to stop the firefighters from entering the burning area.
NS1, am I barking up a tree that does not exsist?
NS1-
I believe you are correct. Imfliximab is licensed for Krohn’s disease and rheumatoid arthritis. However, if I recall, clinical experience has also found an elevated risk of lymphomas and tuberculosis - probably as a result of depressed immunological response.
Many Cats makes a valuable point - attempting to modulate the immune response can have many consequences. Few can be correctly anticipated and some may not even be found in carefully controlled clinicals.. Couple that with an dearth of information on the mechanism of virulence vis-a-vis H5N1, and we probably ought not go there.
Sarge me thinks you are probably correct. We seem to know so little about our immune systems that it might well take a few hundred more years before science reaches that threshold of knowledge. I doubt we’ll be there for this pandemic. Nevertheless, as they say any port in a storm and we shouldn’t necessarily discourage people who want to look at the possibilites. Any agent that gives even marginal protection against the killing rage of this disease is worth atleast speculating on. Personally, I think we already know enough to put some kind of simple plan into effect world-wide. At this juncture we know Tamiflu seems to work we don’t yet know how much is needed but it seems that knowledge will be in our hands soon. As to those who say the disease might mutate it’s way around Tamiflu and Relenza I say what other alternative can you offer? I think it’s worth the gamble to ramp up production of these drugs now on a massive scale and get them into as many hands as possible with a massive educational push on how to use them. It will take guts to do it and yes it’s a gamble but so is most everything else. This is a gamble that if it pays off saves millions of lives.
Mr. White
Keep barking and eventually we’ll find the right tree.
I appreciate that you are self-educating and then sharing the studies you find with all of us. Many are highly relevant to these topics; others may be studied as an adjunct according to the reader’s interest.
The Sarge – at 10:32
The TB and additional spectrum of observed infections post reduction treatment of TNF-alpha and / or NF-kappa is quite explainable as you mentioned due to immune arrest, but still a very real concern.
How many people are carriers of various long term diseases that my re-emerge should we de-activate the innate immune response. 85% of the American population is estimated to carry one of the 8 common forms of Herpesvirus. Consider the range of symptoms of an H5N1 infestation with concurrent HHV-6 or even expression of EBV.
A deeper concern is the considerable evidence of lymphoma.
We can’t conclusively state why lymphoma manifests after TNF-alpha reductive treatment; we don’t fully understand the mechanism. Lymphoma concerns me because of the labile nature of the syndrome . . . it seems to come and go freely in a subject. As such, we should know much more about it than we do, but our knowledge continues to be very limited. Many remissions occur without directed medical intervention.
These mysteries of lymphoma coupled with a therapy that increases lymphoma risk is too hot a box for me to offer my neighbor.
Something for the lay readers would be nice.
Melanie -
Maybe you shouldn’t have mentioned that the combat strength of available mods is down. ;)
Sarge
my novice understanding: is there away for our bodies to be taught to recognize the invading virus early before it reaches the lungs?
I realize that is what a vaccine does, but is there another way to supplement and kick off an early response before the killers t’s come out to do battle and kick our lobes?
is there a substance? enzyme ? that can be introduced to coat/stop the virus from taking hold?
Red yeast rice is a natural statin and it works just well, according to various online sources. It works for me with my diagnosed high cholesterol. I will gather more info to post.
Red yeast is the product of rice fermented with Monascus purpureus yeast. Red yeast supplements are different than red yeast rice sold in Chinese grocery stores. Supplements are manufactured by culturing M. purpureus on rice at carefully-controlled temperature and growing conditions to increase the concentration of mevinic acids. Red yeast contains ten mevinic acids, also known as monacolins, the highest concentration of which is constituted by lovastatin (also referred to as monacolin K or mevinolin). These compounds, which constitute about 0.4% of red rice, competitively inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, blocking cholesterol biosynthesis. Red yeast also contains sterols, including beta-sitosterol, campesterol, stigmasterol, and sapogenin; isoflavones and isoflavone glycosides; and monounsaturated fatty acids. Although the cholesterol lowering effect is likely partially caused by the lovastatin content, it is unclear to what extent. The overall cholesterol-lowering effect of red yeast is likely also the result of the combination of lovastatin, mevinic acids, and other constituents.
Red yeast that is not fermented correctly may contain citrinin. Citrinin is a toxin that may cause kidney failure.
Red yeast is the product of rice fermented with the Monascus purpureus yeast that contains monacolin K (lovastatin, mevinolin) and other HMG-CoA reductase inhibiting compounds. Cholestin (Pharmanex) was one of the most widely studied red yeast products. But the FDA now considers red yeast to be an unapproved drug because it contains a prescription-only statin. Cholestin has been reformulated and now contains policosanol as the active ingredient.
Red yeast should be treated as an HMG-CoA reductase inhibitor, with all the possible side effects, drug interactions, and precautions associated with this drug class. The American Heart Association has cautioned against using red yeast pending the results of long-term studies.
Chemical assay indicates that red yeast products vary considerably in content and concentration of monacolin K and other monocolins.
Source: The Natural Medicines Comprehensive
WOW…not sure exactly what ya’ll are talking about…but it sure sounds sexy. Is the bottom line when you do something to the immune system with statins you might be in more trouble than when you started?
Thanks for sharing your knowledge on this tricky subject.
If you system overreacts, which it will if you are a healthy 18 - 30ish year old. Your system will go into an instant sate of inflammation and cause a cytokines storm.
What a cytokines storm does to the body is essentially creates an absorbent amount of TNF alpha production, which results in the body having an over stimulated immune system. Cytokines are soluble hormone-like proteins that signal cell to cell. This situation causes the body to have a very negative anti-inflammatory reaction. A drug that can combat such as situation is prednisone, however many will not have the ability to receive this drug. Prednisone, a corticosteroid, is similar to a natural hormone produced by your adrenal glands. It often is used to replace this chemical when your body does not make enough of it. It relieves inflammation (swelling, heat, redness, and pain) and is used to treat certain forms of arthritis; skin, blood, kidney, eye, thyroid, and intestinal disorders (e.g., colitis); severe allergies; and asthma. Prednisone also is used with other drugs to prevent rejection of transplanted organs and to treat certain types of cancer. So you may want to know that research from the University of Texas and the National Institute of Health, it was reported that the use of a lei gong teng preparation showed that the herb has anti-inflammatory and immunosuppressive effect comparable to prednisone. Lei gong teng (radix tripterygii wilfordii) is a native plant that grows in many parts of China and Burma. However, be aware that the entire tripterygium plant of which this herb is derived from is highly toxic.
Stains can help suppress this overreaction, that is what all this mumbo jumbo is about. I hope that I helped, or is it still clear as mud …? Sexy….or NOT!?
Source: ME (American Pharmaceutical Association Certified), CDC Dr Friend, Homeland Security Friends, online source that is not longer up…
I want to clarify those posts (SPAM) were not from me, Killer Flu, please check ISP. Do not know this person. Good Luck
Thnaks KillerFlunet
What about doing more research on the use of the homeopathic remedies that the doctors in 1918 used? I read a report somewhere (sorry, don’t remember the source as it was a couple of months ago) that many doctors did not lose any patients or very few and they only used bedrest and homeopathic treatments such as gelsemium and byronium (sp?). The doctors that used aspirin lost a lot of patients (through misuse of the aspirin since it was so new and not realizing that aspirin prolonged clotting time and/or giving too much of it, etc. etc.). Maybe the homeopathics acted in the body by reducing effects of the cytokine storm?
Here’s my two cents:
By the time you think the symptoms are cytokine storm it’s too late to prevent. Science can’t autopsy the immunne system because it’s not an organ. The truth is some people have inherited strong immune system and others got shorted. The big lie is believing it can be controlled. Storm is a cascade effect..many drugs have targeted places in this quick moving event and the event just changes course and activates another pathway.
Anon 22 sees hope in statins for prevention…so far this is the only game in town if it checks out.
This is a teaser about the cytokine storm that affected the volunteers in Britian a few months back. NEJM http://tinyurl.com/gdq66. The full story comes out in September issue.
I have used Red Rice Yeast instead of Rx statins with excellant results. I was wondering if perhaps it might help. Thanks for the info.Will go buy a few more bottles, as I still take it regularly.
Leo7 – at 12:44 Here’s my two cents:
“By the time you think the symptoms are cytokine storm it’s too late to prevent. Science can’t autopsy the immunne system because it’s not an organ. The truth is some people have inherited strong immune system and others got shorted. The big lie is believing it can be controlled. Storm is a cascade effect..many drugs have targeted places in this quick moving event and the event just changes course and activates another pathway.”
THAT is worth a tad more than two cents, IMO.
Leo7.
“By the time you think the symptoms are cytokine storm it’s too late to prevent…”
On the whole, I agree with you…so the question is do animal models of SARS-like illnesses with a cytokine storm count for anything…maybe they do…maybe they don’t.
I’m sure anon 22 will keep an open mind but many medical practioners are too tunnel-visioned and short-sighted to see the whole picture.
If the statins are an effective preventative…great…
…If not I have found prednisolone in my animal model (cattle) to be highly effective at decreasing mortality and chronic sequelae which can be just as important for long-term quality of life.
I would suggest that the best thing medical researchers could do at the moment is talk to veterinary colleges and practising large animal veterinarians to get their opinions on treating the cytokine storm in reference to possible correlations for use in humans…
…the vast knowledge of veterinarians has been under-appreciated and as a result everyone loses in the end.
TOM - Here at the Wiki we think the DVMs are amongst the MOST important voices!! Especially you!!!! We are listening to every word you say!! and truly grateful for your time and contributions!!!!
gharris Thanks.
Tom:
I’m not sure how you’re advocating taking the drug…when? First symptoms? Before symptoms? If the cytokine storm begins I don’t think it can be interupted—no ventilator-no ICU-you die. No one will recover from this without intensive care period. If I saw people dying left and right, I would happily swallow prednislone to prevent it. (In fact if the statins don’t work out and I’m working on the job, I just might demand it).
However, I know it’s bad juju to be taking a steriod and meet a virus…like chicken pox, measles, shingles and flu. Steroids have also been know to reactivate dormant infections. These aren’t rosy scenario’s either in MHO, so I think how long you must take the drug and the dose per kg is crucial.
We need a clincal pharmacist to help us. Anyone here?
Animal models are studied and are often helpful for human use. But all a naysayer has to do these days is point to the experimental study in Britian. The animal studies just didn’t reveal these serious side effects. Do cattle have the same problems with taking steroids and having a close encounter with a virus?
There is one item I would like to discuss. We keep quoting the young age people died at in 1918. We extrapolate the 1918 situation to the present. The death of thousands of soldiers is the primary group that skewed the data. Here’s why; These days we know stress effects the immune system and multiple vaccinations change the immune response as well. Young soldiers going overseas to battle is a no brainer in stress. I’ve found articles stating anywhere from 14–25 vaccines were given to army recruits in 1918. The question being would multivaccines given at once cause the dip in the immune system combined with stress that made H1N1 so deadly to this age group? Could the T-cells have been busy recognizing and buiding defenses against the other antigens that H1N1 was allowed to slip through? Can the immune system get so pumped up from multivaccines that it reaches a ceiling—and there is a natural, temporary reduction of T-cells?
What I’m getting at isn’t antivaccine. I’m suggesting that maybe the C. storm was assisted then, and won’t be the same occurence in H5N1. I understand the frequency of c. storm in children and even in pregnant women. Children have no natural immunity and pregnant women have ramped up immune systems by virtue of being pregnant, and a new virus overwhelmed them. For example, I propose that at least some of the young women who died pregnant could’ve been engaged in a prior antibody-antigen reaction that was common between Rh negative women pregnant with Rh positve children prior to Rhogam (This group would have had a non existent response to flu due to over stimulation). Young people shouldn’t be more susceptible to cytokine storm in my opinion just by virtue of their age. I’m sorry it just doesn’t make sense to me and never has.
If we stay so focused on the 1918 scenario we will still be searching for something that turns off the immune response instead of something that turns on the immune response especially in people with depressed immune response.
I would appreciate any discussion on this topic. thanks
Leo7,
Just a quick answer that won’t do justice to your very insightful questions.
First of all, we are focused on the issue of cytokine storm not BECAUSE of 1918, but because of what is known about the pathophysiology of H5N1.
Secondly, I don’t think that they were given multiple vaccines in 1918. I’ve read some internet posts about that but nothing credible. Can you post your source/links so we can examine this carefully?
Third, you may actually be more right than you know about pregnant woman, but not in the way that you described. It is possible that pregnancies carry with them an alteration of immune responses. But alterations can be up-regulations as well as down-regulations. For example there are some immune-related conditions such as Chronic Fatigue syndrome that tend to get better while the person is pregnant, and then there are other autoimmune or allergic conditions that get worse. Because of the complexities of the immune/cytokine pathways, an up or down regulation of one particular component may trigger a series of reactions that interact on each other and on the original stimulus, such that it is actually quite hard to predict with theoretical models how the outcome might be. Revere in his recent article at Effect Measure on the adverse reactions during Monoclonal antibody trial in London did a good explanation of this concept of unpredictability.
(It’s late and I’m in a hurry, so my grammar goes out the window :-) sorry)
I’m closing this thread because of repeated spam. I don’t know what attracts that, but I’m not going to spend any more time deleting them!