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Dr. Jones: You or someone in your house has painful menstrual cramps. What can you do without going to the drugstore or seeing a professional? This is Dr. Kirtly Jones from Obstetrics and Gynecology at University of Utah Health and this is The Scope.

Announcer: Covering all aspects of women's health, this is the Seven Domains of Women's Health with Dr. Kirtly Jones on The Scope.

Dr. Jones: Menstrual cramps seem to be a uniquely human problem, well female human problem. Of course, part of that is because only primates have a menstrual cycle. Other animals have other biology and don't have nearly as many cycles and even other primates, chimpanzees and gorillas, don't seem to bleed as much or suffer cramps as much as we do.

About two weeks after ovulation if we don't become pregnant, the hormones from the ovary that would have supported an early pregnancy, progesterone or pregnancy, starts to fall and the uterus makes another local hormone called prostaglandins that causes the uterus to cramp, the blood vessels to constrict, and push out the old uterine lining to make way for the new with a bunch of blood that doesn't really seem necessary.

So what can you do right now? A hot but not too hot water bottle on your lower abdomen can be soothing or on your back if you primarily feel the cramps in your back. This was used by our mothers and probably their mothers. It doesn't really heat up your uterus but thermally stimulating the skin can distract other nerve pathways involving pain. Using this principle, a new take on an old device called a transcutaneous nerve stimulator that's been used for chronic back pain, might be useful for period cramps. But we're talking about right here and right now in a hot water bottle or a hot towel and a plastic bag is available to everyone but remember not too hot. Many women get in a hot bath tub and find this is helpful.

Well, what else right now? Well, believe it or not, exercise helps period cramps. Get out and move. A vigorous walk or ride or jog actually decreases the perception of menstrual pain for many women. Of course, if you never do these things, doing them now could be more painful but it will distract you from your cramps. Women who exercise regularly have less perception of menstrual pain, so for right now get up and move and if that doesn't work for you, go get that hot water bottle.

For women who have menstrual periods regularly, there are some habits that may decrease your pain. Some studies have found that decreasing fat in the diet significantly decreasing fat and particularly animal fat can lead to less painful periods. It won't work for you today, but it could be helpful for your next period.

Now personally and scientifically, I wouldn't say that supplements, substances you get in a pill at the health food store, are natural, but some studies found that fish oil decreased the intensity of menstrual cramps. It takes a lot of fish oil, about five pills a day.

A Danish study found that fish oil in combination with vitamin B12 worked better than other oils or placebo. Interestingly the women in the study were women who were chosen because they had bad period cramps. These women had low levels of omega-3 fatty acids in their diet compared to other Danish women. So all of the recommendation for decreasing period cramps is to decrease that in the diet, it may be all about the kinds of fat, less omega-6 from animal and dairy fats, which are associated with inflammation and prostaglandins and more omega-3s from nuts, fish, and seeds, which are anti-inflammatory.

Taking supplements may feel natural to some women but what's in the supplement may not be natural at all and they may contaminant, so be careful. The best choice may come down to dietary choices of low sugar and fat diets with seeds, nuts, and beans as the carbs and healthy oils and fish for the fat.

Of course the category of over-the-counter medicines called NSAIDs, non-steroidal anti-inflammatory drugs such as aspirin, ibuprofen, and naproxen, all work to stop the production of prostaglandins, which cause the cramps. But we're talking about home remedies today.

Remember aspirin was originally isolated from willow bark and teas made from the bark of trees in the willow family have been used by many indigenous peoples to treat pain. Some herbal teas that claim to help period cramps may have some of these substances in them.

So these are some of things you try at home and a few options from the health food store and from the pharmacy section of your grocery store. But two things to consider, if your periods never used to be painful when you were younger and now are increasingly painful or heavy, it's important to see your clinician. Some diseases in the pelvis like endometriosis or fibroids in the uterus can grow and lead to increasingly painful periods.

In medicine we divide painful periods into two categories -- primary painful dysmenorrhea and secondary dysmenorrhea. Primary dysmenorrhea refers to the menstrual cramps that started in early teen hood, the periods were always painful. The good news about primary dysmenorrhea is it gets better as women get older or maybe we just cope with it better.

Secondary dysmenorrhea means you didn't use to have cramps when you were younger and now you do. Secondary dysmenorrhea if it interferes with your daily activity, warrants a visit to your gynecologist.

Lastly if your painful periods interfere with your life and your home remedies and over the counter remedies aren't working, we as gynecologists have some options that are very helpful. Give us a call and thanks for joining us on The Scope.

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Interviewer: DNA tells the story of a 40 million year long battle between primates and deadly pathogens. Up next on The Scope.

Announcer: Examining the latest research, and telling you about the latest breakthroughs. The Science and Research show is on The Scope.

Interviewer: Post-doctoral fellow Matt Barber and Nels Elde, assistant professor of human genetics at the University of Utah, published a paper in the journal Science, documenting an incredible battle for survival between infectious bacteria and primates that has been raging for 40 million years. I'm joined today by Dr. Barber.

Why do you think knowing this story is important?

Dr. Barber: Well, when we think today about emerging resistance of bacteria to antibiotics and we're sort of losing our arsenal of drugs and therapies that we can use against some of these pathogens, and so understanding these sort of new weapons we can use against them I think is really important

Interviewer: I think we're all familiar with the immune responses that our bodies normally mount to fight off infections-- we sneeze, we have to blow our nose. But your story focuses on a different type of response.

Dr. Barber: Right, so what we're talking about here is often referred to as nutritional immunity, so the idea here is that, primarily it's been focused on iron. So iron is an essential nutrient not just for us but for also cellular microbes that inhabit our bodies: so bacteria, fungi, all these guys. So one sort of passive means of immunity is to effectively starve bacteria of nutrient iron. So iron in our body is almost entirely bound by chaperone proteins or other factors that effectively hide this nutrient from potential invading pathogens.

Interviewer: And scientists have actually known about this nutritional immunity for a long time, but I think what your story does is show how important it really is.

Dr. Barber: So what our story is really telling is that really, for at least the last 40 million years of primate evolution and probably in human populations today, is that this battle for iron between bacteria and primates has been a determining factor for our survival as a species.

Interviewer: So how did you go about figuring this out? What was your first clue that this was important?

Dr. Barber: So our story primarily focuses on a primate gene called transferrin. So this is a protein that floats around our blood steams, and it's been known for the last 50 years as the iron transporter in our bodies. So transferrin in the bloodstream binds free iron, transports it throughout the body and delivers it to our cells. But it turns out transferrin is also an abundant source of iron for pathogens.

So we sequenced the transferrin gene from 21 related primate species. So this represents about 40 million years of primate evolution. And then we can use statistical analyses to say, "Are the actual amino acids in this protein rapidly evolving across different species?" And it turns out 16 of the 18 amino acids that we identified were all in this C-lobe of transferrin which really suggested that there was something interesting happening in that part of the gene.

Interviewer: One of the most striking things to me in your paper is this picture of the bacterial protein reaching for iron that is being bound by the transferrin protein, and where these mutations happen is right at that interface, it's like, "Wow, we've got to protect this one spot."

Dr. Barber: Right. So when we have this signature of rapid evolution that leads to the question of what's driving it. Why do we see this at all? And we have some information from the literature that bacteria that steal iron from transferrin, they encode these surface proteins, these receptors called TBPA. This is a receptor that is used by several important human pathogens, so nicera meningitis which is the positive agent of meningococcal disease.

Haemophilus influenzae is a pathogen, if you have kids, they've probably received the Hib vaccine, so this is a potent pediatric pathogen, as well as neisseria gonorrhea which is the causing agent of gonorrhea. So a lot of these important human bacterial pathogens utilize TBPA receptors. What we saw was that, when we mapped the sites that were rapidly evolving in transferrin, all 16 of those sites in the C-lobe under selection were interacting with TBPA.

Interviewer: So you know that these mutations accumulate in one particular spot, and so how do you know that they're really important?

Dr. Barber: I think that the strength of the study came from merging that evolutionary approach and using it as a guide for an experimental biochemical approach. And so what I did was purified transferrin proteins from several different primates. So, for example, we made a single mutation that represents one of the few changes between human and chimpanzee transferrin and that single amino acid, which is also under selection when we look across all primate lineage, that single amino acid was able to block this interaction. So this suggests this is functional genetic differences between humans and chimps, presumably related to bacterial immunity.

Interviewer: You can make some of the mutations you saw in these different primates, you can make them in the lab and show that they actually had an effect.

Dr. Barber: Yes. Exactly.

Interviewer: That must have been kind of a "Eureka" moment for you.

Dr. Barber: That was one of my favorite experiments I've probably ever done in my scientific career.

Interviewer: And of course bacteria aren't going to take this lying down, right?

Dr. Barber: Right. And if we look at the genes for this transferrin receptor, TBPA, across many different bacterial pathogens, it turns out that they also show these signatures of rapid evolution, and it's specifically in the interface of the protein that binds to transferrin. So, this is sort of what we think is seeing the flip side of the arms race from the bacterial perspective.

Interviewer: This story still plays out in the DNA of people alive today.

Dr. Barber: Exactly. Turns out that actually for several decades we've known about variation in the transferrin gene in humans. And so there's a variant of the gene that's called C2. It turns out that the C2 transferrin variant is very abundant. In a room of a hundred people, several people are going to have at least one copy of this gene. And the C2 variant comes down to a single polymorphism, a single amino acid change in transferrin.

And what's really interesting is that C2 transferrin cannot be bound by a receptor from haemophilus influenzae, but it could from some of the neisseria pathogens, like gonorrhea. And so, this was also the start of appreciating some of the underlying genetic variation on the side of the bacteria, that some could not see this human variant and some didn't care.

Interviewer: And I think it's fair to say that if you were just to look at the human DNA sequence, you wouldn't necessarily appreciate kind of the history of what has been going on.

Dr. Barber: That's right. And again, that's maybe another reason why this hasn't been picked up before is that, if we consider studies of human genetic variation we're looking on time scales of maybe thousands or tens of thousands of years. And when we look back, there's potentially no strong signatures of rapid evolution in transferrin within humans, to separate the fact that we see variability. Whereas if we overlay that with 40 million years of primate evolution that we can look at and understand, this sort of gives us a broader perspective on what might be driving some of these interesting changes.

Interviewer: And do you think if we were to do a similar analysis, that our DNA might have other stories to tell?

Dr. Barber: Absolutely. Some other work that I'm doing in the lab is applying the same approach to think about asthma susceptibilities. So for example, people have looked at genes that are different between humans that relate to the ability to develop asthma. And many of these genes are involved in immunity, and if we again look instead of within human populations, if we look across primates, many of these genes appear to be rapidly evolving. So I think this is the tip of the iceberg.

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