Bullseye!

The first 4 months after diagnosis, I went in to the MS Clinic every week for my injection. It took me that long to work up the nerve to stick myself with a needle. The staff a the clinic were patient with me and let me come in until I was ready to do it myself.

Then my (now) ex came in to learn. He took to it like a duck to water. So for a couple of years I alternated injecting my thighs,and the ex would inject my butt and arms. When we split I ended up doing my thighs for 4 years.

After the Wookie and I had been dating for a year and a half, I asked him if he'd like to learn how to do it. I had noticed my thigh muscles seemed to be getting harder to inject, probably from scar tissue, and to be honest, I was tiring of doing it. I really wanted to stop. There was no pain, or next to none, from the injection itself, but the psychological part of it was really beginning to get to me. I just didn't want to do it any more. I didn't want to stop taking medication as I've been able to handle it for the most part, but I needed a break.

So the Wookie began giving me my shots. In the butt. Every week. It was like the weight of the world had been lifted from my shoulders. And so it has been for a couple of years now. Until last month. The Wookie was gone on business for one shot in December and two this month. Oh....my....God......

I discovered (again) how much I despised giving the shot to myself. I am still struggling with why I feel this way about a truly "non event". It's a simple thing to do, there's little discomfort and the side effects are quite manageable at this point. But I can't stand doing it.

The Wookie knows this. And when I get teary eyed about it and try to explain and then get frustrated because I don't know why, he just puts his arm around me and says, "I know". And he has explained that the shot once a week is his way of helping me cope. He's taking some of the burden from me, and as long as the needle isn't going into him, he's fine with it.

Again, a demonstration of how lucky I am. But we MSers may be getting a little more luck thrown our way with the announcement this week of an oral medication to treat MS. I know it is a cancer drug used to treat Hairy Cell Leukemia (HCL) and it has had a successful two year Phase 3 trial. The makers of the drug are hoping to have it on the market in 6 months.

I don't know what the recommendations are for this drug or the side effects or how often it has to be taken. I'm looking into that. I won't be going off the Avonex any time soon though. As long as I have the Wookie to give me the shot, I'll stick to what appears to work for me.

But I do look forward to the day when "Drop your drawers!" is a prelude to something a little more romantic.

S.

Let's Talk about Sex

Here's a posting I know will hike up my stats on the visitor counter. Let's talk about sex. Well, I'll go first, then you can comment if you want to.

In Halifax this weekend is a trade show called The Everything to do with Sex Show. I went yesterday and am going back with the Wookie today. This show has been held in Toronto and Montreal for years and this is its first foray into the uncharted waters of the conservative East Coast. Actually, we're not as conservative as some have deemed us, and there are a number of fetish groups in the city.

The main reason for me attending this show is to get information on methods and devices to aid the disabled community. I have addressed this topic as it related to MS a couple of times at forums for and about MS patients.

Most of the vendors at this show are providers of sex toys, costumes, devices etc., like Fantasia and Sexy Girl. There was a Swinger's Club with a booth set up, the Halifax Sexual Health organization was there with info, there were tattoo folks, hair folks, hair removal folks. You name it, they were there. There's even a dungeon set up by the local BDSM (bondage, discipline, sadism, masochism) community. And there are scheduled talks and demonstrations (though no nudity or sex acts are allowed). It's all very interesting, and the psychologist in me finds a lot of the different communities absolutely fascinating.

Anyway, I am pleased to report that my research has paid off. I have discovered a few things that I will be able to pass on to other MS patients.

For most men with MS, the biggest dysfunction seems to be getting an erection. That's why God invented Viagra. It is of great benefit to those who need it and use it. And docs hand it out quite readily.

For women, sensory issues are a biggie. Some of us (me included), have been subject to those horrendous pins and needles for extended periods of time in the genital area. While the first few minutes may be rather pleasant, the ensuing days or weeks of it can be downright torture. I'm pleased to report that a desensitization product, made by Durex (the condom folks), can be used on women. It was made for men to slow down their ejaculation by slightly numbing the penis, but it can be used safely on women as well. I have yet to meet anyone who has tried the product so can't comment on its effectiveness but it's worth a try.

Lack of sensation is another biggie for women and there are many more products (gels and oils) on the market for that problem. Take your pick.

I came across a couple of products that needed to be explained to me, but I think are absolutely brilliant. They are penis "sleeves" of a sort that enable a person to get a much better grip on the penis with their hands. For those of us with arthritis or muscle contracture of the hands these would be ideal. And one of them even has two little loops attached you can put your fingers through for more dexterity. They reminded me of those "Good Grips" kitchen utensils.

There are tons of vibrators on the market, with different shapes and materials. I even found a waterproof glove with a vibrator in it, and it's very much like swimsuit material so easy to clean and care for.

I have talked to a few MS folks over the years whose spasticity is worsened by orgasm, making it a painful event. Massage before sex can help reduce the occurrence of spasm, though not always, and I often suggest that folks try out different positions to see which has the least negative effect. There are a number of swings, slings, and pillows available to adjust position.

If money is tight (and there does seem to be a large markup on these items), improvise with items found around the house. The glove can be made with a simple bath glove found at the dollar store and one of those little "bullet" vibrators (the waterproof kind) may be put in one of the fingers. Pantyhose, upholstery rope or scarves may be used to manipulate limbs to adjust position, and everyone can use their own pillows as support.

I did talk with a couple of people from the BDSM community. They have suggestions for increasing sensation, from simple over the knee spanking to absolute pain (which I won't get into). There are also electrical stimulants that, again, I won't get into, but I see a possible role in their use for some people.

All the men and women I talked to were open and willing to talk about whatever it is they're into. And the main things that were stressed were consensuality, safety, and respect.

So, links to check out:
Bonnie's Bedroom

Fantasia

Sexy Girl

As for BDSM communities, there are groups in every city. Start with Wikipedia and look for an alternative lifestyle paper in your city. The people who lead these groups are interested in educating folks about their community, so questions you may have about how they may help you are welcomed.

Sex is an important part of the human condition. It is as normal a function as breathing. If you have hangups about talking about it, you won't get the answers or help you need. And you certainly must talk with your partner about it. How can they aid your pursuit of happiness if they don't know what's good or bad for you?

OK, Mom, Dad, if you're reading this and you've gotten this far, you're the coolest!

S.

Haggis and MS

Robert Burns was a poet and a lyricist, widely regarded as the national poet of Scotland. January 25th is Robbie Burns' Day.

Haggis is a traditional Scottish dish made from sheep offal with spices and oats and boiled in a sheep's intestine.

If you are of Scottish descent, Robert Burns is a name you easily recognize. And in Nova Scotia, many folks, not just Scots, celebrate the birth of this poet. Today, we had a friend of mine, Todd, come in to work, bringing with him some haggis and talk with the morning show about the tradition. Todd is a co-owner of a small restaurant and pub in Halifax that the Wookie and I frequent, well, frequently; Stayner's Wharf. Todd and his staff get dressed up for every occasion from Hallowe'en to New Year's to Robbie Burns' Day. He runs a tight ship from what I've seen, and his staff are the nicest, sweetest people you could ever meet. In fact, if you were to come visit me, the first place I'd take you to eat would be Stayner's. They will be serving haggis Saturday night with all the pomp and ceremony of days gone by.

Todd has supported my efforts at fund raising for the MS Society by donating to the Walks and the Bike Tours. (Even if he didn't make donations I'd still be patronizing his establishment.)

Another Scottish tradition is MS. So it's not a tradition in the true sense of the word. But it's a connection many of us share with the Scots. They have one of the highest rates of MS in the world. In fact, most references to genetic factors for MS mention the connection to Northern European countries. The British Isles were subject to invasion by a bunch of different people: Scandinavians, Germanic tribes, and even Iberians (the Spaniards) before that, not to mention the Romans. But it appears the concentration of Northern European invaders may be the ones responsible for propagating MS to the world at large. It's not like they did it on purpose or anything like that, that's just the way it happened. The high concentration of Northern European descendants in Scotland (and Canada) may be one reason for the higher incidence of MS in those countries.

Interestingly enough, haggis may have originated in Scandinavia or ancient Rome and been brought to the British Isles by invaders or other travellers. Kind of like bagpipes. They are typically thought of as Scottish, but their origin may be Middle Eastern, perhaps Turkish or Syrian.

Some may argue that haggis is the Scots' revenge for MS. It is an acquired taste, to be sure, taking getting-used-to. Bagpipes are also an acquired taste. And so is MS, to a degree. Some of us can live with it just fine. But those of us who can live with it, should be advocating for those who can't.

S.

The picture is of a "wild haggis" from Wikipedia. Fictional of course.

Wellsphere

I received a generic-type invite to join Wellsphere. So I did. I am in the company of a number of other MSers, like A Short in the Cord's Joan. This may or may not be a good thing as far as readership goes. But it will definitely be a source of info and ideas. The nifty thing is that my blog automatically loads there. So you can find me everywhere.

I want to welcome new readers from Wellsphere. Come on in, I'll put the coffee on.

The Eyes Have It

For all of my adult life I have been getting my eyes checked every two years. Last night I saw my eye doc and he said he hadn't seen me in 3 years....whoa! Don't know how that happened. Anyway, I had a good check up, everything looks fine. I haven't had optic neuritis and there's no sign of it now.

I had the chance to ask Dr. Cruz about some of his equipment. I specifically wanted to know about the magnification of the tools he uses to look at my eyes. It's 10 times magnification but capable of 60 times (just like my microscope). I told him about the world's best Christmas gift ever, and he was excited, too, as he thinks his kids would like it. I also told him I wanted to check out the Wookie's retina and he said as long as the pupil is dilated I should be able to see it with my microscope. Yay!

Several years ago, probably 7 or 8, I had an ocular event that necessitated an extra trip to Dr. Cruz and then to see a specialist the next day at the hospital. Everything was fine in the end; turns out it was the typical flashes and floaters that usually resolve themselves. But he saw me quickly because of the MS. That's when I found out that he did some research on optic neuritis with a couple of the neuros at the MS clinic in Halifax. Cool. So he knows the players in my health care, and he's done some extra study of the issues particular to MS patients. It was just another example of the horseshoe I have so firmly entrenched in my butt.

It's strange, but I never sought out my current family doc (I got a referral to her from another GP when I was living in another province and planning my move back to Halifax 15 years ago), but, boy, was I lucky to get her. And as for Dr. Cruz, I think I just looked him up in the yellow pages when I needed an eye exam. I got lucky, as I later discovered after the MS diagnosis. Even my dentist is very interested in my MS, reading up on stuff related to it.

And all these folks seem to have an excellent sense of humour, so can appreciate my attitude to most situations. Or maybe they're just being polite, laughing at my jokes and agreeing with my observations.

S.

The pics are one of my eyes and one of the Wookie's.

Cold Silver Lining

It has been freakin' cold this week. Colder than usual. Painful cold. Freeze the tears on your cheeks cold. Driving to work yesterday along the Bedford Basin and the Halifax Harbour I was witness to the phenomenon of "sea smoke". Looking at this took some of the bite from the cold away and I thought I should go out this morning to document it. I'm freakin' crazy, but apparently not the only one as I caught 3 other people out taking pics along the drive.

Into the car by 7:30 on a Saturday morning and it's -21 degrees Celsius. Muttering swear words under my breath I wait for the car to warm up before driving. As I drive, my breath comes out and hits the windshield, condensing first then freezing and blocking my view. So I have to pull over and wait for the windshield to warm up a little more.

Finally, I can see again and I'm off to capture what I hope will be some good photos. Click on the photos to get a better look.






My last stop was back in Bedford, right where the Sackville River empties into the Basin, a favourite spot for a number of ducks, seagulls, and other water birds. I've been in and out of the car a few times and each time, my fingers, despite being encased in gloves, freeze. I caught a glimpse of what appears to be a loon or merganser, too far away to tell, but then a large white bird comes into view. One of the swans!


I don't know which swan this is, as we've had a few living in Bedford over the years, including a mating pair. A few years ago the male died and the following spring the female built a nest anyway. She had no mate, so local folks were concerned that the energy she would expend building the nest and laying (infertile)eggs would hasten her own death. Each time she attempted to rebuild the nest, it was dismantled until she finally stopped. She's been around ever since. I check on her during warmer months but on my training rides last summer around the area she normally resides I never saw her. Is this her? I don't know. But I was so pleased to see this creature this morning I knew coming out so early and in such evil cold was worth it.

S.

A Burden Shared is a Burden Halved

For those of you not familiar with the Carnival of MS Bloggers, please check it out (click on the Carnival button to the right or here). Herrad is the only entry this week. And it's a great one.

Many of us worry about how we may become, or have become, burdens on loved ones. It's why some of us paste smiles to our faces, or never say no to requests, or never ask for help. Forgive me for saying this, but that's a stupid way to live (and I'm as guilty as the next person for not saying no sometimes).

Saying to someone "I'm really not feeling great today, go easy on me" or saying "No, I can't bake cookies for the fair this week" or having your children clean up the kitchen after supper are not bad things at all.

Think how you feel when you've helped somebody. Good, right? Well, give others a chance to feel good, too. Ask for help with the chores, the cookies, or whatever. By allowing yourself to be helped, you are essentially helping someone else.

And there's a difference between making an observation and complaining. In Herrad's case, she says that she does not want to burden everyone with the progression of her MS, but I truly feel she is only making observations of her condition, not burdening her readers. As much as we don't like to face reality sometimes, this is Herrad's reality and the reality for countless others. It must be faced.

It's the reason I speak at every opportunity given to me to raise funds for research and support services. Herrad's reality may some day be mine. And if I don't face that reality, who will?

Leftover Remnants

One of the defining markers of MS is the remnants of "attacks". 11 years after my initial attack, I estimate that I am at about 97%. I still have measurable weakness in my right side and frequent pain in my right side extremities that I can only describe as similar to growing pains. It took only a few months to get back on track physically.Those are the remnants of my first attack.

My second attack, a year and a half after the first, involved the left side of my face. It drooped and chewing was exhausting. But that time it only took a couple of weeks to recover. And I did recover completely, though I do have a remnant from that attack as well; my left nostril occasionally loses feeling (not really a disability; luckily just somewhat annoying to me and interesting to the neuros and my dentist).

We know that the disease modifying drugs lessen the frequency and severity attacks, which in turn means less physical damage to the brain and less disability.

Why we recover in the different ways we do is still a subject of study. Some of us recover quickly from attacks while others don't. Some recover completely, while some are left with what is termed "residual disability" (RD).

I recently read a report on a study that adds support to the use of immunomodulating drugs for patients with MS:

"Findings indicated that RD after 1 year was observed in 54.5% of relapses. As well, higher risk of RD was associated with occurrence of a severe relapse. Incomplete recovery at 1 month was highly predictive of RD at 1 year....

Incomplete recovery at 1 month is a predictor of long-term persistence of RD. Higher relapse severity is also associated with higher risk of RD. Risk of severe relapses is lower in patients treated with immunomodulating drugs."

Every single event that happens in the brain leaves its mark, good or bad, chemically and/or physically altering the landscape of our gray and white matter. We are losing brain volume. Every relapse causes damage. And that damage accumulates, eventually giving us altered abilities. Logic says that reducing the number of relapses is good. Logic says that reducing the severity of relapses is good. The less damage that happens to the brain is good, right?

But what happens if you are medically intolerant of the disease modifying drugs? There are currently studies under way for more than 2 dozen different drugs (besides the DMDs) that show promise. Do some research, ask questions of other MSers who are on different drug regimens, talk to the folks at your nearest MS Society office and ask them to refer you to people willing to share their stories with you. Get information and if you don't understand it, find someone who does. If you're not a "take action" type of person, become one. Pretend it is your young child that needs assistance. You'd move heaven and earth to help your child, so do it for yourself now. You deserve it.

And while you are mulling over all the info and deciding what to do next, you can eat right, sleep well, and exercise.

Most of us have heard our neuro saying that where you are at 5 or 10 years after onset of MS is as good a predictor as any of where we'll be farther in the future. Of course, with MS, prognosis is next to impossible. Information from 10 years ago was predicting that by 19 years after onset, I'd be needing a walking aid of some sort. But since I've been taking one of the disease modifying drugs, I may have altered that prognosis and actually extended the time between onset and need of a walking aid. I'll let you know in 8 years.

S.

Whoops

OK, so I thought I had the video thing figured out but didn't. Will work on getting it to the blog soon....stay tuned.

S.

If a Tree Falls in the Forest...

Kim, at Sunshine and Moonlight posed the question: What happens to lesions when they've disappeared? So I asked the question to Mike, one of the neuro nurses at the MS clinic here in Halifax. The short answer is that they don't disappear, they just stop being active. Because they aren't actively inflamed, they don't show up on the MRI.

Now for the long answer.

Remember, MRI measures water content and water is composed of hydrogen and oxygen. First the MRI machine produces magnetic fields (causing all the hydrogen protons to line up in a certain pattern), then a radiofrequency electromagnetic field is applied. Energy from that second field is picked up by the hydrogen protons, and when the second field is stopped the protons release energy at a radiofrequency that can be detected by the machine. The position of the protons is what is measured. And we get pretty pictures of our insides.

When the protons release energy, they do so at a certain rate. Diseased tissue releases energy at a different rate than normal tissue and this is what is detected by the MRI machine and accounts for us being able to "see" lesions.

So, if a lesion is not detected, does it mean that it's not there? Here we get to that whole tree-falling-in-the-forest thing. An active lesion is one that is inflamed. Now we need an explanation of inflammation.

Inflammation involves the destruction of myelin. Just as when we have an injury to our skin, a number of processes occur. Chemicals and cells rush to the scene to detect "bad" cells and try to eliminate them; at the same time, "good" cells are trying to repair any damage. All this activity is what causes inflammation on our skin and it's much the same in our brains. Inflammation is the process of the body identifying the "bad" cells, eliminating them, then attempting to repair the damage. And if a cell dies in this process it is eaten up and eliminated as well.

All of this activity goes on for days, weeks, and even months before we are even aware we have MS or before we exhibit symptoms. Some lesions may have resulted in permanent injury to the axons of some nerves, what they call axonal degeneration. Shrinking of the brain, called brain atrophy, can occur. Remember, dead tissue is eaten up and eliminated by the body, and in the case of our brains, unlike our skin, it is not regenerated. So we end up with "neurodegeneration" and shrinking of our brain. Scar tissue remains, but there is no activity in it. So the MRI machines can't measure it. The lesion may be gone (when looking at an MRI picture), but the results of its previous activity remain.

So the short answer to "Where do the lesions go?" is nowhere. The scarring remains, damage may be permanent, but there's no activity in that spot of the CNS. At least, none that we are capable of measuring at this point in time.

I hope that answers the question. My concern is with people's "fixation" on lesion counts.

So why do we seem to be so fixated on lesion counts? Because right now, that's all we have to grab on to. That's all we have to physically look at and point to to explain symptoms. By the time we exhibit symptoms, the disease process has already been under way for some time and there's little we can do to repair the damage.

Sounds kind of grim, doesn't it? We know this process is going on continuously, so until we can stop MS, we do what we can to slow down the process of axonal degeneration and brain atrophy. Most of us get a course of steroid treatment in the early stages. The steroids quite often stop inflammation in its tracks, which is why we see such marked improvement with steroids alone (sadly, the risks of continued steroid treatment are too great for it to be used often). OK, so we stop inflammation, now what? You are given a choice of one of many disease modifying drugs. These drugs reduce the number of attacks and their frequency so you will go longer without disability. And that's all we can do right now.

Each attack results in inflammation, which can result in permanent damage and atrophy, so logically, we should try to reduce the number and frequency of attacks. While we are doing that by taking a disease modifying drug, we need to be doing other things to aid our bodies in the repair process. Exercise, eating right, getting enough sleep and rest, and reducing our "bad" stress levels are all things that we can do without expensive drug regimes. Exercise your brain, too, learn different things, or attempt them. It's the attempt that exercises your brain.

GPS For Your Brain

And here we go again....another first for Halifax and the Brain Repair Centre. GPS for your brain. Read the article here.

You might think that Halifax is a hotbed of neuro activity with all the posts lately about this stuff. And you'd be right. Because we have folks like Dr. Mendez who come here to live and work and play, we, as a community benefit. So if you've got a neuro type injury, this is the city you want to be in for treatment.

Much of the same can be said for MS treatment. 11 years ago, as I was being diagnosed I was explaining to my folks how lucky I was to be in this city. With the close relationship the medical school had with the hospitals, the excellent faculty of both schools and hospitals, and emerging treatments for MS, Halifax was the best place in the world to be diagnosed and treated for MS. It still is, I believe.

S.

11 Years On

Now that the Christmas season is over, I can take a bit of a breather. It was fun, but so busy I didn't know some days from others.

I may actually put away the decorations this week (though I only took down the Halloween lights December 24th). My neighbour and I will be doing some purging this month as it's easier to get rid of stuff with an uninterested party aiding you. I hope to find a space to set up my bike besides the living room, though it did serve as a Christmas tree of sorts.

I have a slew of appointments to make for this month: eye doc, dentist, family doc...just regular annual or semiannual checkups but I will have my MS anniversary checkup soon, too. Oh, yeah, happy anniversary to me! This week marks 11 years with MS, though in retrospect, I may have had symptoms 5 years before that. I'll be making chocolate cake of some sort this week to share with the staff at the clinic, and like last year there will be pictures. Stay tuned!

And basketball begins this week. Here's a great shot of the owner of the Rainmen taken by the Wookie at one of the exhibition games recently:


We'll be attending the games with our friends Kathy and Jane, which in itself is a hoot. These gals have the same sense of humour we do, poor things.

S.

Let Them Eat Dirt

For almost 11 years I have been wondering what MS is good for, or to put it in other terms, how did MS evolve into what we know it as today?

Who or what organism benefits from a body having MS?

I have spoken about the "hygiene hypothesis" on this blog and the use of worms (called helminths) in possibly treating MS and other auto-immune disorders. Studies are currently under way to see if these creatures are truly beneficial to people with MS. If they are, we need to understand why. Do the worms provoke a type of response that protects from MS symptoms? If so, how?

I came across the "old friends" hypothesis recently and it is related to the hygiene hypothesis. Friendly microorganisms exist all over the world and in our guts. We eat them, drink them, and breathe them in without being aware of it. But we are an obsessed society these days, with improved sanitation and potable water systems, anti-bacterial soaps, and germaphobia, so many of these organisms don't stand a chance of surviving. There appears to be evidence that these "old friends" are needed to build and maintain healthy immune systems. And perhaps the presence of these "old friends" affects our own gene's expressions. If we don't have them, our genes are activated and ta-da! MS appears.

Humans have evolved to the point where we need certain microbes to live in and on us in order for us to maintain our health. If we didn't have the myriad of creatures living with us that we do, the world would be a lot less habitable.

We have been investigating the "viral" theory of MS for years; in other words, we are exposed to a virus that years later provokes an immune response we identify as MS. Maybe we should be looking at what we are missing from our bodies that causes MS. A virus may be the ultimate culprit for MS but what if there's another organism that by its mere existence in our system, battles the virus' long term effect on our immune system and stops the development of MS?

Scientists have identified certain genes that may be involved in MS. How they are activated remains to be seen. But it could be the simple presence of micro-organisms that keep them in line. So now I have to rethink my original question and perhaps look at who doesn't get MS and why not.

The other part of this post comes from an article I came across about a microorganism that when ingested seems to boost serotonin levels.

Researchers first spotted the special effects of the bacterium, Mycobacterium vaccae, when they used it to help treat patients with lung cancer. They discovered that the bacterium reduced the patient's pain and increased their feelings of well-being.
Lead researcher Dr Chris Lowry explains: 'We thought this might be due to some affect on serotonin in the brain - a chemical that affects happiness. It's a really important chemical and low levels of serotonin can lead to depression in some people.'
We injected the bacteria into mice and found that it had a very similar effect on them as antidepressant drugs such as Prozac', says Chris Lowry. 'The bacteria were triggering an immune response in the body which somehow led to an increase of serotonin in the brain.
'This response was really specific. The bacteria were activating groups of nerve cells that produce serotonin in the areas of the brain that regulate mood and brain function, but no where else. This was what was really striking to us - we didn't expect that,' he explains.
The scientists think their results could help unravel why immune system upsets can lead to depression in some people. But before they can put the bacteria to work treating depression, they need to do some more investigations.
'But before conducting clinical trials on people we need to understand exactly how this works. We believe that the bacteria may trigger sensory nerves in our body that send information back to the brain, causing the increase in serotonin. But at the moment we're really not sure.'
Other experts agree this could be an important step. 'If you take a drug like Prozac, you are setting off all the serotonin neurons, some of which can cause nasty side effects like insomnia,' says Graham Rook, an expert in Immunology at University College London.
'But this response is very specific and activates just the neurons that affect depression. If you could work out the exact molecular mechanisms by which this bacterium works you could find a whole new way of treating depression.'

To sum everything up: eat dirt, it's good for you.

S.