Brain: Protein That Regulates Key ‘Fate’ Decision in Cortical Progenitor Cells Identified

Researchers at Cold Spring Harbor Laboratory (CSHL) have solved an important piece of one of neuroscience’s outstanding puzzles: how progenitor cells in the developing mammalian brain reproduce themselves while also giving birth to neurons that will populate the emerging cerebral cortex, the seat of cognition and executive function in the mature brain.

CSHL Professor Linda Van Aelst, Ph.D., and colleagues set out to solve a particular mystery concerning radial glial cells, or RGCs, which are progenitors of pyramidal neurons, the most common type of excitatory nerve cell in the mature mammalian cortex.

In genetically manipulated mice, Van Aelst’s team demonstrated that a protein called DOCK7 plays a central regulatory role in the process that determines how and when an RGC “decides” either to proliferate, i.e., make more progenitor cells like itself, or give rise to cells that will mature, or “differentiate,” into pyramidal neurons. The findings are reported in the September 2012 issue of Nature Neuroscience.

DOCK7 was already known to be highly expressed in various parts of the developing rodent brain, including the hippocampus and cortex. It had been shown by Van Aelst and colleagues to control the formation of axons — wiring that connects neurons.

Balancing proliferation and differentiation

In their newly published research, Van Aelst, along with Drs. Yu-Ting Yang and Chia-Lin Wang, a graduate student and postdoctoral fellow, respectively, in the Van Aelst lab, elucidate DOCK7’s regulatory role in experiments in which the protein was alternately silenced and overexpressed.

When the protein was silenced in mouse embryos, neuronal differentiation was impeded; RGCs remained in their progenitor state. When DOCK7 was overexpressed, RGCs differentiated prematurely, resulting in more neurons and fewer RGCs.

These and related experiments revealed the mechanism through which DOCK7 expression affects the two essential but contrasting functions of RGCs. “Self-renewability of RGCs must be tightly balanced with differentiation for proper cortical development,” says Van Aelst.

“The mechanism we discovered to be central in the determination of RGC fate is called interkinetic nuclear migration, or INM,” she continues, “and you can see it in action in the movies made by Drs. Wang and Yang.”

In INM, an RGC cell nucleus visibly travels over the course of the cell cycle “upward” and “downward” between opposing sides of the apical-most region of the neuroepithelium, called the ventricular zone or VZ. Nuclei move away from the apical surface during the G1 phase, undergo S phase at a basal location in the VZ, and return to the apical surface during G2 to divide at the apical location. [see diagram below]

It is DOCK7 that regulates this movement; in particular, the movement from the basal to apical location, the CSHL team has now demonstrated. On what appears to be the lower surface of the VZ, the apical surface, signals directing the RCG toward proliferation — i.e., reproduction of other RGCs — are dominant. On the upper or ‘basal’ side of the VZ, dominant signals coax the RGC to split into new intermediate progenitors or neurons.

Migration explained: DOCK7, TACC3 and centrosomes

“The cellular machinery that controls INM involves a protein complex of actin and myosin, called actomyosin, as well as microtubule-dependent systems,” notes Dr. Wang. “We show how DOCK7 exerts its effects by antagonizing the microtubule growth-promoting function of a protein called TACC3.” That protein, tellingly, is associated with the centrosome, the cellular organ that organizes microtubules, and regulates the growth of microtubules emanating from the centrosome, thereby coupling the centrosome and nucleus .

As Dr. Yang points out, DOCK7 acts by antagonizing the microtubule growth-promoting function of TACC3. Silencing of DOCK7 accelerates the movement of RGC nuclei from the basal to apical side of the VZ, resulting in extended apical residency of RGC nuclei and apical mitoses that lead to an increase in RGCs and a reduction in neurons. DOCK7 overexpression, on the other hand, leads to extended residence of RGC nuclei at basal locations and mitoses away from the apical surface, where the production of new neurons increases, at the expense of the proliferation of more progenitors.

Beyond elucidating an important mechanism of cortical development, the new research may shed light on pathologies seen in microcephaly, a condition marked by an abnormally small brain size, as well as neurodevelopmental disorders such as schizophrenia. “If DOCK7 expression is abnormal, you perturb normal neurogenesis,” says Van Aelst. “In future work we hope to explore whether an imbalance in neurogenesis caused by DOCK7 aberrations is associated with a subsequent imbalance in cortical circuitry, and various known pathologies.”

Source: science daily.



Removing the Optimism Bias.

Disrupting a small part of the brain with a magnetic field can reduce people’s prejudice towards good news.

Humans tend to embrace good news, while discounting bad news. We overestimate our odds of winning the lottery or living long lives, while underplaying our risk of cancer, divorce, or unemployment. Now, researchers from University College London (UCL) have found a way of removing these rose-tinted glasses, by aiming a magnetic field at a brain region called the left inferior frontal gyrus (IFG). Their results are published today in the Proceedings of the National Academy of Sciences.

“So much of the work on psychological biases over the decades has been correlational,” said Dominic Johnson, a political scientist from the University of Oxford, who was not involved in the study. “Here we have a rare example of a direct manipulation experiment. This is a great step forward and promises to open up whole new avenues for research in this area.”

The optimism bias was recognised decades ago, and seems to exist across genders, nationalities, races, and ages. UCL’s Tali Sharot has been studying how the brain creates this bias since 2007. In an earlier study using functional magnetic resonance imaging (fMRI), she had linked the IFG to people’s ability to update their beliefs with new information. “The left IFG was tracking information that was better than expected, and the right IFG was tracking information that was worse than expected,” she said, “and [the right IFG] wasn’t doing as efficient a job.”

“But fMRI only gives us a correlation,” Sharot added. “To show causation, we wanted to see whether manipulating these brain regions would alter how people learn from good and bad information.” She and UCL colleague Ryota Kanai used transcranial magnetic stimulation (TMS)—a technique for temporarily shutting off part of the brain—to disrupt the right IFG, the left IFG, or an unrelated area in 30 volunteers. Five minutes later, the researchers asked the volunteers to estimate their chances of experiencing 40 different nasty fates, from Alzheimer’s disease to robbery. Sharot and Kanai then revealed the actual frequencies of each event and, later, asked the volunteers to recalculate their estimates.

Optimism bias was alive and well among volunteers receiving TMS to the right IFG or the unrelated region, who were more likely to update their beliefs when the bad events were less common than expected. But such bias vanished in the group whose left IFGs were disrupted who, on average, gave equal weight to statistics showing that events were either more or less likely than they had expected. Questionnaires revealed that TMS did not affect other traits that could have explained the volunteers’ changed behavior, such as emotional arousal or negativity. Nor did the treatment affect their memory—they were just as likely to remember the actual probabilities that they had been told, no matter where the magnetic fields were aimed.

Based on her earlier work, Sharot thought that disrupting the left IFG would reduce the optimism bias by reducing our ability to learn from good news, while disrupting the right IFG would boost a person’s inclination towards good news. Her results showed otherwise. In fact, with the left area shut down, people were just as likely to adjust their beliefs based on good news, but better at adjusting their beliefs based on bad news.

“There are many implications of such research, from potential mechanisms of depression at a personal level, to ignoring financial errors at a societal one,” said Daniel Bor, a neuroscientist from the University of Cambridge, who did not participate in the research. However, he added, “previous research in this area has more implicated the right, rather than the left, IFG. More research needs to be carried out to further validate and explore this intriguing finding.”

Sharot and Kanai also found some individual variations. Even though disrupting the left IFG negated optimistic tendencies on average, 40 percent of the volunteers still showed the bias. “This raises interesting questions about whether some people have a greater or lesser ability to resist cognitive biases,” said Johnson, although he noted that “some of this variation is likely due to noise or the treatment not working for whatever reason.”

Of course, it may not always be beneficial to suppress such natural biases. Unwarranted optimism can lead us to take unnecessary risks with our health or finances, but Sharot and Kanai noted that it could also be adaptive, by encouraging people to try new things or avoid the stress of potential illness or failure.

In certain cases, however, Sharot thinks that her work might have clinical relevance. Targeting the right brain area could, for example, help boost optimism in people who tend to lack it, such as those with depression. “If you start off in depressed individuals, my hypothesis would be that disrupting the right IFG would create a bias that isn’t there,” she said.

T. Sharot et al., “Selectively altering belief formation in the human brain,” Proceedings of the National Academy of Sciences, doi:10.1073/pnas.1205828109, 2012.



Researchers create the first atlas of gene activity in the human brain.

An international team of researchers has created a high-resolution, 3-dimensional map of gene expression in human brains, using donated, whole brains from two males and a single hemisphere from a third man’s brain, according to a new study published last week (September 19) in Nature.

The researchers, led by Michael Hawrylycz of the Allen Institute for Brain Science in Seattle, created the atlas by assembling transcription data—collected using DNA microarrays—from around 900 precisely cut brain pieces and overlaying them on MRI brain scans of the donated brains taken before dicing. The maps—freely available online—could help scientists test hypotheses of brain function, disease, and evolution.

“By themselves these data do not hold all of the answers for understanding how the brain works,” Ed Lein, a neuroscientist at the Allen Institute and co-author of the study, told LiveScience. “However, we hope they serve as a catalyst in human brain research for understanding the brain’s complex chemistry and cellular makeup.”

For example, scientists studying particular disorders could use imaging techniques, such functional MRI, to assess brain areas involved, then consult the new atlas to evaluate the genes expressed in those regions, which are displayed by a simple, color-coded guide to show the relative level of gene expression. Currently researchers rely on piecemeal studies of mouse brains for such expression information.

Coauthor Seth Grant of Edinburgh University told BBC News that for brain research to progress it is “essential to understand how it makes all of the genes and where they are expressed in the human brain.”




Fear Can Be Erased from the Brain, Research Shows.

Newly formed emotional memories can be erased from the human brain. This is shown by researchers from Uppsala University in a new study now being published by the academic journal Science. The findings may represent a breakthrough in research on memory and fear.

Thomas Ågren, a doctoral candidate at the Department of Psychology under the supervision of Professors Mats Fredrikson and Tomas Furmark, has shown, that it is possible to erase newly formed emotional memories from the human brain.

When a person learns something, a lasting long-term memory is created with the aid of a process of consolidation, which is based on the formation of proteins. When we remember something, the memory becomes unstable for a while and is then restabilized by another consolidation process. In other words, it can be said that we are not remembering what originally happened, but rather what we remembered the last time we thought about what happened. By disrupting the reconsolidation process that follows upon remembering, we can affect the content of memory.

In the study the researchers showed subjects a neutral picture and simultaneously administered an electric shock. In this way the picture came to elicit fear in the subjects which meant a fear memory had been formed. In order to activate this fear memory, the picture was then shown without any accompanying shock. For one experimental group the reconsolidation process was disrupted with the aid of repeated presentations of the picture. For a control group, the reconsolidation process was allowed to complete before the subjects were shown the same repeated presentations of the picture.

In that the experimental group was not allowed to reconsolidate the fear memory, the fear they previously associated with the picture dissipated. In other words, by disrupting the reconsolidation process, the memory was rendered neutral and no longer incited fear. At the same time, using a MR-scanner, the researchers were able to show that the traces of that memory also disappeared from the part of the brain that normally stores fearful memories, the nuclear group of amygdala in the temporal lobe.

‘These findings may be a breakthrough in research on memory and fear. Ultimately the new findings may lead to improved treatment methods for the millions of people in the world who suffer from anxiety issues like phobias, post-traumatic stress, and panic attacks,’ says Thomas Ågren.

Source: science daily.

The Prepregnancy Diet.

Now that you’re trying to conceive, it’s time to overhaul your eating habits. Here’s how to get started.

Are you gearing up for baby-making? Here are five things you can do to improve your diet and safeguard your (and your baby-to-be’s) health.

1. Become a fool for folic acid (folate). Studies show that the earlier you start getting enough of this vital vitamin — ideally, during preconception — the lower the chances that your baby will develop neural tube defects (such as spina bifida). Where can you find folic? Most leafy green vegetables and whole grains are naturally full of it — plus, it’s added to most refined grain products (by law). Want extra insurance? Taking a prenatal supplement is an easy way to buy it — and when it comes to folic acid, you can’t be too careful (after all, a three-salad-a-day habit is a worthy goal — but one you may not always manage to reach). Since you’re in this for the long haul, and even after you’ve overhauled your eating habits, a supplement can be the most realistic way to fit folic acid in day after day after day (especially once you find those days filled with nausea). Choose a prenatal supplement with 400 to 600 mcg (micrograms) of folic acid to be sure you’re getting your fill.

2. Junk the junk food. Reduce refined sugars and white flour (in the form of your usual suspects — cookies, doughnuts, Danish, cake, candy, and almost anything else you might grab from the vending machine, the coffee cart, the convenience store racks, the pastry shop display case…you get the picture). Slash saturated fats (sub a side salad for the fries; grilled chicken for the extra crispy) — less is better for your baby, plus a high intake of such fats appears to increase the risk of severe pregnancy nausea and vomiting. (Uh, thanks but no thanks.)

3. Relish the right stuff. Increase all the good things that your body (and your baby-to-be’s body) needs: green leafies (those delicious salads), yummy yellows (apricots, carrots, papaya, mango), hearty whole grains (whole-wheat bread, brown rice, oatmeal), and low-fat dairy. (Got milk? Yogurt? Cheese? You should!)

4. Stop being a meal skipper. Are you always more interested in catching the train than breaking for breakfast? Working through lunch instead of eating it? Skip a meal when you’re eating for two (which you soon will be) and baby skips it too. Get into the three-squares habit now so that when baby’s on board, he or she will be getting a steady supply of nutrients throughout the day.

5. Take a clear-eyed look at your dietary habits. Might any of them stand in your way of eating well? Do you think you might have an eating disorder that needs prepregnancy treatment, such as anorexia nervosa or bulimia? Are you on a restricted diet (either self-imposed or due to a chronic condition) that might need to be adapted once you’re eating for two, such as macrobiotic, vegan, or diabetic? Now’s the time to discuss any of these factors with your practitioner — and to enlist the help of a dietitian if your eating habits need reshaping. Support groups (especially in the case of an eating disorder) can also help you get your nutritional status back where it should be.

Decaffeinate Your Diet

Decreasing your caffeine intake can increase your chances of conception. So make that java a decaf and read on!

Crave that morning mochaccino — with four shots of espresso? Can’t get through the afternoon without that cola (or two, or three)? If you’re thinking about getting pregnant, you should think about living a less-caffeinated life. You’ll need to curb the caffeine during pregnancy anyway (too much caffeine isn’t good for you or your baby), so it’s a good idea to get a head start on decaffeinating now, since cutting down may actually help you get (and stay) pregnant. Experts believe that high caffeine intake (more than five cups a day) may trigger miscarriage. And some studies have linked downing too much caffeine to lowered fertility.

What’s too much caffeine when you’re trying to conceive? Technically, more than 200 mg a day. Too technical for you? Here are some figures to help you see how quickly it adds up. A cup of brewed coffee can contain more than 100 mg of caffeine and a 12-ounce soft drink more than 50 mg. (Which means your Mountain Dew just became a Mountain Don’t.) You’ll also find caffeine (if you look) in nonherbal teas (whether it’s iced, brewed, or green), energy drinks (80 mg in a can of Red Bull!), chocolate, and some over-the-counter cold and allergy drugs. Even coffee-flavored ice cream or yogurt packs a modest caffeinated punch.

There’s no need to cut caffeine out altogether if you’re planning on becoming pregnant or even once you become pregnant — most experts believe that two cups a day is fine. If you need to cut down (or would like to cut it out), slow is the way to go. Rather than shocking your system into extreme exhaustion by quitting abruptly, gradually lower your caffeine intake. Substituting decaf for some of each cup you normally drink will start you on the weaning process. Keep reducing the amount of regular and increasing the amount of decaf until your cups are completely caffeine-free. Another way to cut back on the caffeine in your cup: Make it a latte. Cut the coffee back to half a cup and fill it to the brim with hot skim or low-fat milk.

Eating smaller, more frequent meals will help during this process because that will keep your blood sugar raised — and, hence, your energy levels up. Prenatal vitamins will also help you maintain your stamina without a caffeine fix, as will regular exercise.

Bone Up on Calcium

You know calcium does a body good, but it’s good for your baby-to-be too — even before you conceive.

Got milk? To increase your odds of getting pregnant, it’s important to get a good dose of calcium (plus the vitamin D that comes with it) every day. Not only is calcium essential for your teeth and bones, it will strengthen your baby-to-be’s developing bones and teeth and help muscle, heart, and nerve development as well.

How to bone up? Milk is an obvious source of calcium (and an especially efficient one if you select calcium-fortified skim milk). Can’t bear the thought of drinking the white stuff straight up? Disguise it in smoothies and soups instead. Or dabble in other dairy sources, like yogurt (straight from the container, in smoothies, or as a topping for fruit) and cheese (munch on a mozzarella stick with crackers, sprinkle Parmesan on your pasta, pour low-fat cheese sauce over steamed vegetables).

Does dairy not do it for you at all? If you’re lactose intolerant, you can take calcium supplements, drink calcium-fortified orange juice with your breakfast, eat a canned salmon salad (mashed up with the bones) for lunch, and snack on edamame (soybeans).

Here’s a list of surefire calcium-rich options (along with a few surprises) — aim for three servings daily.

  • Low- or nonfat milk, cheese, or yogurt
  • Nonfat dry milk (mix into soups, baked goods, or smoothies)
  • Orange juice with added calcium
  • Soy milk and tofu
  • Broccoli
  • Kale, mustard, or turnip greens
  • Dried figs
  • Cooked dried beans
  • Almonds, filberts, or peanuts
  • Corn tortillas (check labels and choose a brand with the most calcium)
  • Sesame seeds

The Dos and Don’ts of Eating Fish

Serious about seafood? It’s important to know which fish to pick and which to pitch when you’re trying to conceive.

Seafood and fish are filled to the gills with protein, vitamins, and heart-healthy omega-3 fatty acids — essential nutrients when you’re on the prepregnancy diet. But when you’re trying to conceive, you need to keep a keen eye on the fish you fry (or, better yet, broil or grill), because some fish contain dangerously high levels of the heavy metal mercury, a toxin that can damage the nervous system. Here are some easy ways to net the benefits of a fish-friendly eating plan:

Try for twelve. According to the Food and Drug Administration, women who are pregnant or working on getting pregnant (if you can call it work) should eat no more than 12 ounces (but some experts recommend less of most fish or shellfish per week). That’s two six-ounce servings of, say, chunk-light tuna, or one and a half servings of a typical fish steak or fillet — in other words, about two meals per week.

Know your fish. As you may have caught on, there’s even more to this fish story: The FDA says that shrimp, salmon, pollack, and catfish are good catches, while swordfish, shark, tilefish, and king mackerel have high levels of mercury and should be tossed back. Albacore tuna and tuna steaks have more mercury than chunk light in a pouch or can, but if you limit yourself to about one serving of either per week, you should be fine.

Use a cheat sheet. Having trouble remembering what’s tame and what’s toxic? The Monterey Bay Aquarium offers a life preserver with its handy, printable pocket-size list of fish and seafood that are good choices, good alternatives — or good to avoid (for a variety of reasons, including overfishing, damaged habitats, and, of course, pollutant levels).

Consider supplements. The omega-3 fatty acids found in fish and seafood are good not only for your heart — they’re great for growing healthy babies too. Studies show the oily omegas prevent preterm labor, preeclampsia, and improve the baby’s visual and cognitive functions. Experts also believe that there’s a connection between low DHA (omega-3’s) and postpartum depression. But if you’re not a fan of the fishy taste or are worried about too much mercury, you may be able to take fish oil capsules or a prenatal vitamin with omega-3’s instead. Ask your practitioner what he or she recommends. Some prenatal vitamins now get their omega-3’s from algae, an all-natural plant source of DHA, which makes them a great option for vegetarians. Another good option: DHA eggs, which are fortified with omega-3’s from flaxseed fed to laying hens.

Healthy Vegetarian Eating

Have a beef with eating beef? Wondering if you’ll have to trade in your soy for sirloin now that you’re trying to conceive? Fortunately for you and your dietary principles, the answer is no. Babies born to vegetarian moms are just as healthy as those born to carnivores. You can remain meatless (and fishless, and eggless — even dairyless) and still have a healthy preconception and pregnancy — as long as you get the right amounts of certain key nutrients. Discuss your diet with your practitioner, take a prenatal vitamin, and pack your plate with these essentials, which are typically trickier for vegetarians to tap into. If your partner is a fellow vegetarian, make sure he’s getting his fill of these nutrients as well — shortfalls could slow your conception success!

  • DHA: This omega-3 fatty acid is crucial for brain and nervous system development and found in fatty fish such as salmon but also in such vegetarian favorites as DHA eggs and algae.
  • Zinc: This mineral helps keep sperm and eggs healthy and is critical for the production, repair, and functioning of DNA — pretty darn important for a pregnant mom or wannabe! Get it from fortified cereal or cooked dried beans or peas.
  • Folic acid: Also known as folate or vitamin B9, this mineral can prevent neural tube defects such as spina bifida. Good vegetarian sources are leafy greens, legumes, papaya, and strawberries.
  • B12: Since vitamin B12 is found only in foods that come from animals, strict vegetarians will have to get it in supplement form, or from special soy milks, cereals, and meat substitutes that are B12-fortified. (If you are already taking a prenatal vitamin, ask your practitioner if you need extra B12.)
  • Protein: Vegetarians who eat eggs and dairy usually have no problem getting enough protein (though it’s important to note that these protein sources are not as efficient as fish and poultry). But vegans may have to work a little harder at it and look to dried beans, peas, tofu, and other soy products to ramp up the protein.
  • Iron: It helps your body make blood (which you need a lot of when you’re pregnant) and maintain a healthy immune system. Cook in a cast-iron pan when you can, and try these vegetarian-friendly sources of iron: fortified cereal, oatmeal, legumes, tofu, and spinach. Talk to your practitioner about taking an iron supplement too.
  • Calcium: Just like Mom always said, milk builds strong bones and teeth — yours and your baby’s. But if you don’t eat dairy, then get your calcium from fortified soy products, fortified OJ, leafy greens, even dried figs and corn tortillas.
  • Vitamin D: D is a team player — working with calcium on bone- and tooth-building. Though you can get some vitamin D from sunlight — and fortified milk — as a vegetarian, you’ll probably need a supplement.















Could Oral FacialTherapy Be the Answer for Sleep Apnea?

Not sleeping well? You’re not alone… A recently published study1 from Sweden highlights just how common more severe sleep problems, like sleep apnea, might be. Apnea is a Greek word that means “breathe.” Sleep apnea is the inability to breathe properly, or the limitation of breath or breathing, during sleep.

The study, which included 400 women ranging in age between 20-70, found that hmycoalf of them had mild to severe sleep apnea. Among women with hypertension or who were obese, the numbers were even higher – 80 to 84 percent of them had sleep apnea. This is significant, as sleep apnea is tied to higher risks of stroke, silent brain infarction2, heart attack, and early death.

As reported by Reuters:3

“Each apnea event was defined by at a least a 10-second pause in breathing accompanied by a drop in blood oxygen levels. Women who had an average of five or more of these events during each hour of sleep were considered to have sleep apnea.

The study, which was funded by the Swedish Heart Lung Foundation, found that apnea became more common in the older age groups. Among women aged 20-44, one quarter had sleep apnea, compared to 56 percent of women aged 45-54 and 75 percent of women aged 55-70.

…Severe sleep apnea, which involves more than 30 breathing disruptions per hour, was far less common. Just 4.6 percent of women 45-54 and 14 percent of women 55-70 had severe cases. Among women of all ages with hypertension, 14 percent had severe sleep apnea, and among women who were obese, 19 percent had severe apnea.”

What is Sleep Apnea?

There are three general types of sleep apnea described in the medical literature:

  • Central apnea, which typically relates to your diaphragm and chest wall and an inability to properly pull air in
  • Obstructive apnea, which relates to an obstruction of your airway that begins in your nose and ends in your lungs
  • Mixed apnea is a combination of both

Obstructive sleep apnea consists of the frequent collapse of the airway during sleep, making it difficult for victims to breathe for periods lasting as long as 10 seconds. Those with a severe form of the disorder have at least 30 disruptions per hour. Not only do these breathing disruptions interfere with sleep, leaving you unusually tired the next day, it also reduces the amount of oxygen in your blood, which can impair the function of internal organs and/or exacerbate other health conditions you may have.

Signs and Symptoms of Sleep Apnea

Your body is constantly working to keep you alive – it’s in constant CPR mode, if you will. So at night, your body is constantly shifting and compensating to keep you breathing. One sign that you’re having trouble breathing is when your body compensates with increased forward head posture when sleeping. The worse your apnea gets, the more pronounced this forward posture becomes, because pulling your head forward helps compensate for the lack of room behind the back of your tongue.

Another common compensation that can indicate sleep apnea is frequent tossing and turning at night. This is because when you’re laying on your back, gravity will pull your jaw and tongue backward, further into your throat, which can obstruct breathing. Hence, tossing and turning may be your body’s way of keeping you breathing.

Snoring is another indication that you may have sleep apnea.

A simple test you can perform to check whether or not you’re breathing properly is to stand with your back against a wall, with your heels, buttocks, shoulder blades and head touching the wall. Say “Hello,” swallow, and then breathe. If you can speak, swallow, and breathe easily and comfortably in this position, then your mouth and throat are clear. If you cannot perform those three functions, your breathing is probably obstructed, which may be exacerbated when lying down to sleep.

Of course you could also have a professional evaluation in a sleep laboratory for a more comprehensive diagnosis. One useful new inexpensive tool for under $100 is the Zeo, which is available on Amazon. It is essentially a sleep lab that you can perform every night. It will not only tell you how long you are sleeping but when you wake up, how long you are up for, the length and times of your REM, light, and deep sleep. It then provides you with a summary sleep score that can tell you how well you slept during the night. You can then use this information to help fine tune your sleep program and monitor the effectiveness of any intervention.

You Don’t have to Be Obese to Suffer from Sleep Apnea

Years ago, sleep apnea was thought to be primarily associated with morbid obesity, which clearly can be a significant contributing factor. However, many patients diagnosed with sleep apnea today do not have a weight problem. So what’s really causing your sleep apnea?

The primary issue appears to be related to the shape and size of your mouth, and the positioning of your tongue.

The conventional treatment for sleep apnea is a machine called CPAP, which is an acronym for “continuous positive airway pressure.” The machine creates a forceful pressure that mechanically opens up your airway. But that does not address the cause of the problem, although it may provide some symptom relief.

According to Dr. Arthur Strauss, a dental physician and a diplomat of the American Board of Dental Sleep Medicine, our mouths have progressively gotten smaller through the generations due to lack of breastfeeding and poor nutrition. Breastfeeding actually helps expand the size of your child’s palate and helps move the jaw further forward – two factors that help prevent sleep apnea by creating more room for breathing. Diet is also important. Dr. Weston Price‘s pioneering work showed how diet can affect your entire mouth, not just your teeth.

If your sleep apnea is related to your tongue or jaw position, specialty trained dentists can design a custom oral appliance to address the issue. These include mandibular repositioning devices, designed to shift your jaw forward, while others help hold your tongue forward without moving your jaw. However, sleep apnea relief may also be found in the form of speech therapy treatment…

Oral Myofunctional Therapy Shown Effective for Sleep Apnea

My girlfriend, who is in no way obese, has suffered from obstructive sleep apnea for most of her adult life and it had nearly destroyed her physical health from insomnia. I recently became aware of a form of therapy called oral myofunctional therapy, which appears to have great promise for the treatment of sleep apnea. Essentially, it’s an exercise program for your mouth and tongue.

I had interviewed a dental hygienist, Carol Vander Stoep, and while in our video studio she quickly evaluated me and told me I was “tongue tied” and that it might be affecting my health. I was surprised, so I obtained an evaluation by Joy Moeller, the leading orofacial myologist in the US, and she confirmed it. So I consulted with her and started on some mouth exercises and in less than a week I noticed a remarkable improvement in my time in deep sleep as objectively measured by the Zeo. The program takes about one year to change the muscles and increase the size of the oral cavity to decrease obstructive sleep apnea, but I actually may have been suffering from this my whole life and never knew it. I will certainly keep you posted of my progress.

Although this therapy is widely known in Brazil, it is relatively unheard of in the US. As Joy explains:4

“Myofunctional therapy, also called orofacial myology, is the neuromuscular re-education or re-patterning of the oral and facial muscles. It might include muscle exercises, which create a normal freeway space dimension. Therapists are trained to eliminate negative oral habits through behavior modification techniques and promote positive growth patterns. We train people to breathe through their noses if their airways are not compromised, and if the oral breathing is an acquired habit; we teach people how to properly position their tongue at rest; we teach how to chew and swallow correctly, and we emphasize the importance of proper head and neck posture patterns.

…Therapy usually starts with establishing nasal airway (after clearance from an ENT and an Allergist) and developing a lip seal. If a patient habitually breathes through his/her mouth, the tongue rests down and the mandible drops down and back. The palate, in turn, might not develop correctly. A good myofunctional therapist will assist the patient to clear his/her nose, use correct abdominal (diaphragmatic) breathing, and then establish habitual nasal breathing.”

According to a 2007 case report published in International Archives of Otorhinolaryngology:5

“Speech therapy treatment could be considered a new therapy for snoring and obstructive sleep apnea patients because of its direct action on oral motility. The myofunctional therapy includes the correct use of the stomatognatic structures and functions by means of functional exercises (respiratory, suction, swallowing and chewing) and muscular exercises with the aim of increasing the tonus and mobility of oral and cervical structures, which can be damaged in apneic patients.”

The paper includes the case histories of two subjects, one male and one female, both of whom experienced “extreme regression of the syndrome.”

Home Testing Technologies

Myofunctional therapy strikes me as an excellent first step if you suspect you might have sleep apnea, before you start sinking money into sleep studies, expensive machines, and/or oral surgery. Furthermore, there are technologies available that can help you determine whether or not you may have a problem that may require seeing a specialist. These home technologies can also be used to evaluate how well an oral appliance is working. For example, you can:

  • Measure your snoring with iPhone apps
  • Record the sounds of you sleeping using Audacity, a free software program available online
  • Measure your blood oxygen levels with an oximeter. Oftentimes, if you have sleep apnea, you’re going to have a drop in blood oxygen. When it drops to a certain level, it indicates you have a problem

To learn more about sleep apnea, check out the American Academy of Dental Sleep Medicine’s website. Dental sleep medicine is an area of medicine that focuses on the management of sleep-related breathing disorders.

Source: Dr. Mercola


Alzheimer’s May be Caused by Poor Diet.

The cause of the debilitating, and fatal, brain disease Alzheimer’s is conventionally said to be a mystery.

While we know that certain diseases, like type 2 diabetes, are definitively connected to the foods you eat, Alzheimer’s is generally thought to strike without warning or reason.

That is, until recently.

Now, a growing body of research suggests there may be a powerful connection between the foods you eat and your risk of Alzheimer’s disease and dementia, via similar pathways that cause type 2 diabetes.

Some have even re-named Alzheimer’s as “type 3 diabetes.”

Can You Eat Your Way to Alzheimer’s?

In a recent animal study, researchers from Brown University in Providence, Rhode Island were able to induce many of the characteristic brain changes seen with Alzheimer’s disease (disorientation, confusion, inability to learn and remember) by interfering with insulin signaling in their brains.1

Faulty insulin (and leptin, another hormone) signaling is an underlying cause of insulin resistance, which, of course, typically leads to type 2 diabetes. However, while insulin is usually associated with its role in keeping your blood sugar levels in a healthy range, it also plays a role in brain signaling. When researchers disrupted the proper signaling of insulin in the brain, it resulted in dementia.

What does this have to do with your diet?

Everything, as over-consumption of sugars and grains is what ultimately causes your body to be incapable of “hearing” the proper signals from insulin and leptin, leaving you insulin resistant in both body and brain.

Alzheimer’s disease was tentatively dubbed “type 3 diabetes” in early 2005 when researchers learned that the pancreas is not the only organ that produces insulin. Your brain also produces insulin, and this brain insulin is necessary for the survival of your brain cells.

If You Have Diabetes, Your Risk of Alzheimer’s Increases Dramatically

Diabetes is linked to a 65 percent increased risk of developing Alzheimer’s,2 which may be due, in part, because insulin resistance and/or diabetes appear to accelerate the development of plaque in your brain, which is a hallmark of Alzheimer’s.3 Separate research has found that impaired insulin response was associated with a 30 percent higher risk of Alzheimer’s disease,4 and overall dementia and cognitive risks were associated with high fasting serum insulin, insulin resistance, impaired insulin secretion and glucose intolerance.

A drop in insulin production in your brain may contribute to the degeneration of your brain cells, mainly by depriving them of glucose, and studies have found that people with lower levels of insulin and insulin receptors in their brain often have Alzheimer’s disease (people with type 2 diabetes often wind up with low levels of insulin in their brains as well). As explained in New Scientist, which highlighted this latest research:5

“This new focus [on the Alzheimer’s/diabetes/insulin connection] follows a growing recognition of insulin’s role in the brain. Until recently, the hormone was typecast as a regulator of blood sugar, giving the cue for muscles, liver and fat cells to extract sugar from the blood and either use it for energy or store it as fat. We now know that it is a master multitasker: it helps neurons, particularly in the hippocampus and frontal lobe, take up glucose for energy, and it also regulates neurotransmitters, like acetylcholine, which are crucial for memory and learning.

What’s more, it encourages plasticity – the process through which neurons change shape, make new connections and strengthen others. And it is important for the function and growth of blood vessels, which supply the brain with oxygen and glucose.

As a result, reducing the level of insulin in the brain can immediately impair cognition. Spatial memory, in particular, seems to suffer when you block insulin uptake in the hippocampus… Conversely, a boost of insulin seems to improve its functioning.

…this role in the brain ‘makes evolutionary sense,’ since it would help us to remember the location of a food source. As our ancestors gorged on berries in the savannah, for instance, the spike in glucose and the subsequent rush of insulin would signal ‘remember this, it’s important,’ causing the brain to crystallise the memory.

But as we know from type 2 diabetes, processes that evolved to help us meet the challenges of prehistory can easily backfire in the modern world.

When people frequently gorge on fatty, sugary food, their insulin spikes repeatedly until it sticks at a higher level. Muscle, liver and fat cells then stop responding to the hormone, meaning they don’t mop up glucose and fat in the blood. As a result, the pancreas desperately works overtime to make more insulin to control the glucose – and levels of the two molecules skyrocket.

…The pancreas can’t keep up with the demand indefinitely, however, and as time passes people with type 2 diabetes often end up with abnormally low levels of insulin.”

Alzheimer’s Might be “Brain Diabetes”

It’s becoming increasingly clear that the same pathological process that leads to insulin resistance and type 2 diabetes may also hold true for your brain. As you over-indulge on sugar and grains, your brain becomes overwhelmed by the consistently high levels of insulin and eventually shuts down its insulin signaling, leading to impairments in your thinking and memory abilities, and eventually causing permanent brain damage.

You may already know I have become passionate about warning of the dangers of fructose. There is NO question in my mind that regularly consuming more than 25 grams of fructose per day will dramatically increase your risk of dementia and Alzheimer’s disease. Consuming too much fructose will inevitably wreak havoc on your body’s ability to regulate proper insulin levels.

Although fructose is relatively “low glycemic” on the front end, it reduces the affinity for insulin for its receptor leading to chronic insulin resistance and elevated blood sugar on the back end. So, while you may not notice a steep increase in blood sugar immediately following fructose consumption, it is likely changing your entire endocrine system’s ability to function properly behind the scenes.

Additionally, fructose has other modes of neurotoxicity, including causing damage to the circulatory system upon which the health of your nervous system depends, as well as profoundly changing your brain’s craving mechanism, often resulting in excessive hunger and subsequent consumption of additional empty carbohydrate-based calories.

In one study from UCLA, researchers found that rats fed a fructose-rich and omega-3 fat deficient diet (similar to what is consumed by many Americans) developed both insulin resistance and impaired brain function in just six weeks.6

Plus, when your liver is busy processing fructose (which your liver turns into fat), it severely hampers its ability to make cholesterol, an essential building block of your brain crucial to its health. This is yet another important facet that explains how and why excessive fructose consumption is so detrimental to your health.

Since the average American is exceeding this recommendation by 300% this is a pervasive and serious issue. I view significantly reducing fructose consumption as the MOST important step you can take to lower your risk of Alzheimer’s disease.

More Tips for Avoiding Alzheimer’s Disease

The beauty of following my newly revised Nutrition Plan is that it helps treat and prevent all chronic degenerative diseases, from the common ones like heart disease, cancer, diabetes, obesity and Alzheimer’s to the ones you have never heard of or can’t even pronounce. So please read the Plan as soon as you can. It is divided into three helpful sections, Beginner, Intermediate and Advanced to help you start at the right level.

The plan is the first step in addressing Alzheimer’s disease, which is currently at epidemic proportions, with 5.4 million Americans – including one in eight people aged 65 and over – living with the disease.7 By 2050, this is expected to jump to 16 million, and in the next 20 years it is projected that Alzheimer’s will affect one in four Americans.

In spite of how common memory loss is among Westerners, it is NOT a “normal” part of aging. While even mild “senior moments” may be caused by the same brain lesions associated with Alzheimer’s disease and other forms of dementia, these cognitive changes are by no means inevitable! People who experience very little decline in their cognitive function up until their deaths have been found (post-mortem) to be free of brain lesions, showing that it’s entirely possible to prevent the damage from occurring in the first place… and one of the best ways to do this is by leading a healthy lifestyle.

  • Fructose. As mentioned, most everyone will benefit from keeping their total fructose consumed to below 25 grams per day.
  • Improve Magnesium Levels. There is some exciting preliminary research strongly suggesting a decrease in Alzheimer symptoms with increased levels of magnesium in the brain. Unfortunately most magnesium supplements do not pass the blood brain levels, but a new one, magnesium threonate, appears to and holds some promise for the future for treating this condition.
  • Optimize your vitamin D levels with safe sun exposure. Strong links between low levels of vitamin D in Alzheimer’s patients and poor outcomes on cognitive tests have been revealed.8 Researchers believe that optimal vitamin D levels may enhance the amount of important chemicals in your brain and protect brain cells by increasing the effectiveness of the glial cells in nursing damaged neurons back to health.

Vitamin D may also exert some of its beneficial effects on Alzheimer’s through its anti-inflammatory and immune-boosting properties. Sufficient vitamin D is imperative for proper functioning of your immune system to combat inflammation that is also associated with Alzheimer’s.

  • Keep your fasting insulin levels below 3. This is indirectly related to fructose, as it will clearly lead to insulin resistance. However other sugars (sucrose is 50% fructose by weight), grains and lack of exercise are also important factors.
  • Vitamin B12: According to a small Finnish study recently published in the journal Neurology,9 people who consume foods rich in B12 may reduce their risk of Alzheimer’s in their later years. For each unit increase in the marker of vitamin B12 (holotranscobalamin) the risk of developing Alzheimer’s was reduced by 2 percent. Very high doses of B vitamins have also been found to treat Alzheimer’s disease and reduce memory loss.
  • Eat a nutritious diet, rich in folate, such as the one described in my nutrition plan. Vegetables, without question, are your best form of folate, and we should all eat plenty of fresh raw veggies every day.
  • High-quality animal-based omega-3 fats, such as krill oil. (I recommend avoiding most fish because, although fish is naturally high in omega-3, most fish are now severely contaminated with mercury.) High intake of the omega-3 fats EPA and DHA help by preventing cell damage caused by Alzheimer’s disease, thereby slowing down its progression, and lowering your risk of developing the disorder.
  • Avoid and remove mercury from your body. Dental amalgam fillings, which are 50% mercury by weight, are one of the major sources of heavy metal toxicity, however you should be healthy prior to having them removed. Once you have adjusted to following the diet described in my optimized nutrition plan, you can follow the mercury detox protocol and then find a biological dentist to have your amalgams removed.
  • Avoid aluminum, such as antiperspirants, non-stick cookware, vaccine adjuvants, etc.
  • Exercise regularly. It’s been suggested that exercise can trigger a change in the way the amyloid precursor protein is metabolized,10 thus, slowing down the onset and progression of Alzheimer’s. Exercise also increases levels of the protein PGC-1alpha. Research has also shown that people with Alzheimer’s have less PGC-1alpha in their brains11 and cells that contain more of the protein produce less of the toxic amyloid protein associated with Alzheimer’s. I would strongly recommend reviewing the Peak Fitness Technique for my specific recommendations.
  • Avoid flu vaccinations as most contain both mercury and aluminum, well-known neurotoxic and immunotoxic agents.
  • Eat plenty of blueberries. Wild blueberries, which have high anthocyanin and antioxidant content, are known to guard against Alzheimer’s and other neurological diseases.
  • Challenge your mind daily. Mental stimulation, especially learning something new, such as learning to play an instrument or a new language, is associated with a decreased risk of Alzheimer’s. Researchers suspect that mental challenge helps to build up your brain, making it less susceptible to the lesions associated with Alzheimer’s disease.
  • Avoid anticholinergic and statin drugs. Drugs that block acetylcholine, a nervous system neurotransmitter, have been shown to increase your risk of dementia. These drugs include certain nighttime pain relievers, antihistamines, sleep aids, certain antidepressants, medications to control incontinence, and certain narcotic pain relievers.

Statin drugs are particularly problematic because they suppress the synthesis of cholesterol, deplete your brain of coenzyme Q10 and neurotransmitter precursors, and prevent adequate delivery of essential fatty acids and fat-soluble antioxidants to your brain by inhibiting the production of the indispensable carrier biomolecule known as low-density lipoprotein.

Source: Dr. Mercola




Incidental detection of late presenting co-arctation of the aorta on chest x-ray: the importance of rib notching.


A 31-year-old obese male presented to the emergency department with symptoms and signs suggestive of a viral upper respiratory tract illness with a background of low exercise tolerance. Rib notching was identified on plain film chest radiography and subsequent CT of the thorax identified a moderately tight 2-mm juxta-ductal co-arctation of the aorta with multiple enlarged chest wall collaterals. The patient underwent a two-stage percutaneous procedure involving stent insertion and angioplasty up to 16 mm with significant improvement in exercise capacity and a modest reduction in blood pressure.


Incidental detection of rib notching on plain film radiography led to a diagnosis of co-arctation of the aorta in a male patient. Subsequent endovascular intervention resulted in improvements in the patient’s exercise capacity and energy levels and prevented the development of disastrous complications such as aortic dissection and cardiac failure.

Estimating the pretest probability of the presence of co-arctation of the aorta is difficult when non-specific symptoms such as lack of energy and low exercise capacity are found on clinical assessment. Radio-femoral delay is the clinical sign classically associated with co-arctation of the aorta, but in the present case the trigger was rib notching found on chest radiography.

This case is important as co-arctation can be missed during postnatal screening or develop late. Clinicians and radiologists therefore need to be aware of rib notching.

Case presentation

A 31-year-old obese male presented to the emergency department with shortness of breath, productive cough, chest pain, nausea and vomiting over a 4-day period. The cough was productive of green sputum. The chest pain was sharp, worst posteriorly and brought on by coughing but not on deep inspiration. His breathlessness did not limit his daily functioning, although a subjective background of lifelong reduced exercise tolerance was noted. Significantly, three family contacts had symptoms of viral upper respiratory tract infection over 2 weeks prior to presentation. There was no recent travel history. There was a chronic history of reduced exercise tolerance, intermittent headaches, leg cramps on exertion and a childhood heart murmur, but none of these were considered significant enough to require further investigation. There was no history of hypertension or diabetes. Family history was positive for ischaemic heart disease in his mother. He was on no regular medications. He was employed as an IT worker with a background in nursing, was married with three young children, was a non-smoker and consumed two to three standard drinks of alcohol per week.

On examination his blood pressure was 150/90 mm Hg, pulse was 90 bpm with a regular rhythm, respiratory rate was 19/min and temperature was 36.9°C. Cardiovascular examination revealed impalpable femoral pulses, a grade 1/6 systolic murmur and soft, non-tender calves. Respiratory examination revealed chest wall tenderness on palpation manoeuvres and right lower zone crepitations on auscultation.

These clinical features were most in keeping with an acute upper respiratory tract infection.


Initial investigations included laboratory tests (cell counts and troponin), a 12-lead ECG and plain film chest radiography. Blood investigations were negative except for an elevated white cell count consistent with an acute infection. The 12-lead ECG revealed T-wave inversions in leads V4–V6, unchanged from a previous ECG.

The chest film revealed rib notching of the under surfaces of mid and upper-thoracic ribs), a cardiothoracic ratio at the upper limit of normal and bilateral peribronchial cuffing in the lower zones consistent with bronchitis. The presence of borderline cardiomegaly and rib notching raised the possibility of aortic co-arctation or chronic anaemia.

Cardiovascular MRI revealed an unrestricted bicuspid aortic valve and left aortic arch with normal branching pattern. There was enlargement of the right brachiocephalic trunk, left subclavian artery and internal mammary arteries with large intercostal vessels collateralising the distal aorta. Mild tubular hypoplasia of the aortic arch was also noted.

Differential diagnosis

The differential diagnosis of rib notching includes vascular and non-vascular causes. Vascular causes are due to enlarged collateral intercostal vessels to the distal aorta, which subject adjacent ribs to greater pressure than usual, resulting in bony erosion. Implicated vessels can be arterial as in aortic co-arctation and Takayasu’s arteritis, venous as in superior vena cava obstruction or arteriovenous as seen in arteriovenous fistulae. Non-vascular causes of rib notching include neurofibromatosis, intercostal neuromas and pseudo-rib notching where irregular cortical thickening may occur in the presence of tuberous sclerosis and hyperparathyroidism. Degrees of rib notching on chest radiography may also be of no clinical significance.

Treatment, outcome and follow-up

Preprocedural imaging consisted of cardiovascular MRI, cardiac CT angiogram and transthoracic echocardiogram. The patient underwent an uncomplicated endovascular aortic stent graft with left brachial artery and right femoral artery puncture with a 4×4 mm balloon angioplasty following an intravenous heparin bolus of 5000 IU. A Cheatham stent was deployed up to 10 mm at the level of the co-arctation and 16 mm distal to the co-arctation site. Six months after this procedure the patient reported improvement in exercise tolerance without chest pain, palpitations or leg cramps. His blood pressure was 135/80 mm Hg, slightly reduced compared with initial presentation (150/90 mm Hg) and femoral pulses were palpable bilaterally. CT angiography of the aorta revealed a patent stent without evidence of displacement or narrowing.

Twelve months after the initial procedure the patient underwent an uncomplicated percutaneous transluminal angioplasty of the thoracic stent up to 18 mm. Nine months after the angioplasty he reported further improvements in exercise capacity with no recurrence of chest pain or leg cramps. His blood pressure was 130/80 mm Hg. Echocardiography revealed normal left ventricular function with residual mild left ventricular hypertrophy. Follow-up management consisted of cardiovascular risk factor optimisation including caloric intake reduction to accompany increases in exercise as well as close monitoring of blood pressure. The patient was well at the time of writing, 32 months after the angioplasty.


Co-arctation of the aorta is the sixth most common congenital heart condition in Australia, with 92 cases recorded in 2003 at a rate of 3.6 per 10 000 live births.1 Diagnosis in adulthood is rare and has been associated with high mortality. Of those surviving past early childhood, historical data indicate 25% die before age 20, 50% by age 32, 75% by age 46 and 90% by 58 years.2 The most common cause of death was congestive heart failure, followed by aortic rupture, bacterial endocarditis and intracranial haemorrhage.2

Survival depends on the development of a collateral blood supply from the subclavian arteries (preco-arctation) to the aorta distal to the co-arctation via anastomoses with the intercostal arteries via three pathways: (1) the scapular pathway, including the transverse scapular and transverse cervical arteries originating from the thyrocervical trunk as well as the subscapular artery arising from the axillary artery; (2) the external thoracic pathway, including thoracic branches from the axillary artery; and (3) the internal mammary arteries3 (figure 4). Collateralisation is evidenced on chest x-ray as rib notching, which has been long associated with co-arctation of the aorta. The first three and last two ribs are typically spared due to their blood supply arising from branches unaffected by the co-arctation.

The sensitivity and specificity of rib notching for co-arctation of the aorta have not been defined. The first parameters concerning the utility of rib notching come from a case series of 43 patients with co-arctation of the aorta diagnosed at autopsy aged 2 years or greater from 1946.6 Some 75% of these 43 subjects had recognisable rib notching, giving a false negative rate of 25%. More recently, signs of a collateral circulation (rib notching and/or a visible internal thoracic artery) were seen in 26/38 patients with co-arctation of the aorta (68%, indicating a false negative rate of 32%)7 in one study, rib notching was seen in 39/61 patients (64%, false negative rate of 36%) in another8 and there is also case report evidence of co-arctation of the aorta without rib notching.9 These reports of false negative results of rib notching demonstrate limits to its sensitivity, but there are also reports that rib notching has limited specificity for co-arctation of the aorta despite a lack of numerical data. Rib notching has been visualised in the presence of other cardiovascular pathologies,3 non-vascular pathology4 and in up to 19% of healthy individuals10 (so-called pseudo rib notching).

There are also no reports on the sensitivity and/or specificity of radio-femoral delay, the classic examination sign associated with co-arctation of the aorta. Assessment for radio-femoral delay requires patients to uncover their groin area which may be a disincentive for clinicians in busy settings; additionally, locating femoral pulses can be difficult particularly in obese patients.11

An anecdotally reported alternative to radio-femoral delay involves comparing upper and lower limb systolic blood pressure,11 seeking a differential of at least 20 mm Hg.9 12,,16 Sensitivity and specificity for co-arctation of the aorta have not been calculated for this technique either, and its specificity is likely to be limited by the rarity of adult co-arctation of the aorta, especially with the comparatively high prevalence of peripheral arterial disease which can alter the ankle–brachial pressure index.17

Other signs which may aid the detection of co-arctation of the aorta include comparison of capillary refill times and temperature between the upper and lower limb extremities.18

Despite the uncertain relative utility of these techniques, it is important to be aware that each can be associated with co-arctation of the aorta and may warrant focused assessment and further investigation.

Learning points

  • ▶ As co-arctation of the aorta can be missed during or develop after screening, clinicians and radiologists need to be aware of rib notching.
  • ▶ Co-arctation of the aorta may present without hypertension and with non-specific symptoms of headache, low exercise capacity and intermittent leg cramps, which may not be considered significant enough for further investigation.
  • ▶ Rib notching may be seen in co-arctation of the aorta due to enlarged collateral intercostal arteries and while not specific, mandates the consideration of co-arctation.
  • ▶ Measurement of differences in lower limb and brachial arterial pressure is a reasonable and simple alternative to femoral pulse palpation but may be confounded by peripheral arterial disease.
  • ▶ Capillary refill and temperature differences between the upper and lower limb extremities may also indicate co-arctation of the aorta.


Dr Jenny Ho (Central City Medical Centre, Perth, Western Australia) is thanked for her support.


  • Competing interests None.
  • Patient consent Obtained.


Australian Institute of Health and Welfare 2011. In: Cardiovascular disease: Australian facts 2011. Cardiovascular disease series. Cat. no. CVD 53. Canberra: AIHW 2011.

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Ovarian ectopic pregnancy.


The authors report the rare case of a 25-year-old female who suffered from an ovarian ectopic pregnancy. She presented at 10 weeks gestation with a 1-day history of vaginal bleeding and lower abdominal discomfort. β-human chorionic gonadotropin concentration was 8538 IU/ml. Ultrasound showed a right adnexal mass 4.0 × 3.8 × 5.5 cm with a 16 mm cystic area suggesting right ovarian ectopic pregnancy. Diagnostic laparoscopy confirmed a ruptured right ovarian ectopic pregnancy with haemoperitoneum. This was excised laparoscopically. She made a good postoperative recovery and was discharged on the second postoperative day. Histology confirmed a ruptured ovarian ectopic pregnancy. Ovarian ectopic pregnancy is a rare condition. There are two features that make this an unusual case; the relatively late gestation at which she presented and her mild presenting features. Unlike tubal ectopic pregnancies, which usually present at earlier gestations, this patient presented relatively late. She also presented with mild symptoms and signs.


Ovarian pregnancy is a rare condition and high index of suspicion is needed. Ovarian pregnancy comprises 0.15% of all pregnancies and 1–3% of ectopic gestations.1

Clinical diagnosis can be difficult and challenging. If an ovarian pregnancy ruptures, mortality is quite high.

In this case of right ovarian pregnancy, the clinical findings were mild and not characteristic of an ectopic pregnancy. She attended accident and emergency earlier on in the day and was discharged. This case illustrates how an ovarian pregnancy can be easily missed and the patient can even be discharged.

Case presentation

A 25-year-old female at 10 weeks gestation (spontaneous conception) in her fourth pregnancy presented to accident and emergency department with vaginal bleeding and lower abdominal discomfort. There was no history of dizzy spells or faintness. There was no history of vomiting, bladder or bowel problems. She had used Implanon as her contraception and had come off just a month prior to her last menstrual period. She had irregular periods while on Implanon. She had two previous uneventful pregnancies and vaginal deliveries at term and one previous termination of pregnancy.

There was no significant medical history. There was no history of pelvic infection or any gynaecological procedures apart from surgical termination of pregnancy which was done in 2004 after which she had spontaneous conception and vaginal delivery at term in 2006.

There was no significant family history.

On examination, her observations were all within normal limits. Her abdomen was soft and she had some mild tenderness in her right loin, right iliac fossa and suprapubic areas. On speculum examination, the cervical os was closed and only minimal bleed was noted. On vaginal examination, she had no cervical excitation and no adnexal tenderness. She was explained although ectopic pregnancy is always a possibility but in her case in absence of tenderness threatened spontaneous abortion was most likely diagnosis. She was discharged from accident and emergency with appointment of Early Pregnancy Assessment Unit in 1 week’s time for ultrasound scan of pelvis. But this patient presented again in few days to accident and emergency with increasing discomfort in right loin area. She was admitted to the gynaecology ward and had ultrasound scan next day which clearly suggested right ovarian ectopic pregnancy.


Serum β-human chorionic gonadotropin (β-HCG) concentration was 8538 IU/l. Haemoglobin was 11.3 g/dl on admission, then 9.9 g/dl postoperatively. Microbiology swabs were negative for Chlamydia, Gonorrhoea and Candida. Urine dipstick was negative for nitrites and leucocytes.

Transvaginal ultrasound scan suggested a normal uterus, endometrial thickness of 7 mm, normal left ovary and adnexa. Adjacent to right ovary there was a 4.0 × 3.8 × 5.5 cm mass with 16 mm cystic area within it consistent with ectopic pregnancy. Laparoscopic findings showing ruptured ectopic pregnancy.

Differential diagnosis


The patient underwent a diagnostic and therapeutic laparoscopy and the right ovarian ectopic pregnancy was resected laparoscopically with conservation of more than two-thirds of her right ovary

Outcome and follow-up

She had an uneventful procedure. Despite the ectopic pregnancy being adherent to right ovary still her right ovary was conserved. She had good postoperative recovery and was discharged home on the second postoperative day.


We conducted a Medline search for reports of ovarian ectopic pregnancy and found approximately 100 cases; however, many of them being related to fertility treatment, intrauterine devices or tubal ligation.

The incidence of ectopic pregnancies is 1%.2 Among these ectopic pregnancies, ovarian pregnancy is quite rare, constituting 1–3% of all ectopic pregnancies.3 It is the most important cause of maternal death in the first trimester accounting for approximately 10% of deaths related to pregnancy.4

The aetiology of ovarian pregnancy remains unclear, it occurs as a result of a fertilised ovum getting implanted on the ovarian tissue. Although several factors, such as pelvic inflammatory disease and previous gynaecological surgery, are closely linked to tubal pregnancies but do not seem to be related to ovarian pregnancies.5 6 Ovarian ectopic pregnancies have been mostly associated with high parity, younger age and people receiving in-vitro fertilisation treatment.7 9 It has been found that intrauterine device use and ovulation induction are the most common risk factors for ovarian ectopic pregnancy.8 10 11

The clinical findings of ectopic pregnancy include secondary amenorrhoea, abdominal pain and vaginal haemorrhage, with a clinical picture of varying acuteness.12 It has been reported that the presentation of ovarian ectopic pregnancies can be delayed.5 13

This case meets all the diagnostic criteria as described by Spiegelberg:

  1. An intact fallopian tube on the affected side
  2. A gestational sac must occupy the normal position of the ovary
  3. The ovary and gestational sac must be connected by the utero-ovarian ligament to the uterus
  4. Histological confirmation of ovarian tissue in the gestational sac wall.10

Investigation is mainly with transvaginal ultrasound scan which can detect ovarian ectopic pregnancy. However, ultrasound scan may not be able to diagnose all cases of ovarian pregnancy due to anatomical location.

Laparoscopy is the gold standard for both investigation and therapeutic intervention.1 It is the treatment of choice for haemodynamically stable patients.1 The aim should be to conserve the ovary on which the ectopic pregnancy is attached to by doing an ovarian cystectomy or wedge resection.12 Patients who are haemodynamically unstable would need an urgent laparotomy.12 Methotrexate is a good alternative to laparoscopic management in unruptured ovarian ectopic pregnancy; however, it’s toxicity has to be taken into account.14

Learning points

  • ▶ Ovarian ectopic pregnancy can present with mild pain and tenderness and very subtle clinical findings and can therefore be easily missed and even discharged, posing a big diagnostic challenge.
  • ▶ One should have a high index of suspicion of ovarian ectopic pregnancies even when the patient has no risk factors.
  • ▶ Ovarian ectopic pregnancy can have a delayed presentation compared to tubal ectopic pregnancies.
  • ▶ In the case of an ovarian ectopic pregnancy, the ovary can be conserved in many cases.


    1. Tinelli A,
    2. Hudelist G,
    3. Malvasi A,
    4. et al

. Laparoscopic management of ovarian pregnancy. JSLS 2008;:16972.


Royal College of Obstetrics and Gynaecologists. The Management of Tubal Pregnancies. Guideline 21. London: RCOG, 2004.

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Source: BMJ.

Rupture of bicornuate uterus.


A primigravida aged 20 years was referred to Vydehi Institute of Medical Sciences with diagnosis of 30 weeks of period of gestation with eclampsia and failure to respond to induction with misoprostol and she was on Pritchard regimen for the treatment of eclampsia and there was no response to induction of labour and emergency ultrasound was taken and it showed an extrauterine gestation of 30 weeks gestation with fetal demise and free fluid in peritoneum. A tentative diagnosis of secondary abdominal pregnancy with eclampsia was made and she was taken for emergency laprotomy. Intra operative findings showed haemoperitoneum, fetus with placenta and membranes in the peritoneal cavity, there was bicornuate uterus and right horn was ruptured from the fundus to about 8 cm down in the posterior aspect and ruptured part was sutured in two layers. After securing perfect haemostasis, abdomen was closed. This paper illustrates a case report of uterine anomaly with 30 weeks period of gestation and eclampsia and rupture following induction with prostaglandins.


Pregnancy with uterine anomolies is rare in clinical practice and only few cases are reported in literature. Most of the obstetricians do not keep it in mind during induction of labour. In developing countries like India majority of the pregnant women are not booked for early antenatal care due to financial constraints. Most of the uterine anomalies go unnoticed because they are often symptomless. Majority are first recognised during pregnancy and judicious use of prostaglandins should be advocated in unbooked cases.

This paper illustrates a rare case of rupture of bicornuate uterus following induction with prostaglandins and gives us a message that antenatal diagnosis of uterine anomalies is very important to prevent rupture in later pregnancy and uterine anomalies should be kept in mind when there is failure of induction of labour.

Case presentation

Primigravida aged 20 years presented to a private hospital with two episodes of convulsions and she was treated there with magnesium sulphate with Pritchard regimen1 and labour was induced with misoprostol. Four doses of misoprostol 50 microgram were inserted pervaginally 4 hourly, but there was no progress of labour and emergency ultrasound was taken and it showed an extra uterine gestation of 30 weeks gestation with fetal demise and free fluid in peritoneum. The patient was referred to Vydehi Institute of Medical Sciences for further management. Her married life was 2 years and she has not taken any antenatal visits. Her personal and family history was not significant.

At presentation, the patient was pale, drowsy, irritable, with grade 2 pedal oedema, blood pressure was 110/70 mm hg and thready pulse was 104 beats per min. Her respiratory and cardiovascular examinations were with in normal limits. Central nervous system examination patient was drowsy, irritable and deep tendon reflexes were present. The abdomen was very tender and irregularly shaped with easily palpable fetal parts and the fetal heart sounds could not be heard. Vaginal assessment revealed scanty vaginal bleeding and cervical os was 2 cm dilated and soft in consistency. The station of the presenting part could not be made out and there was tenderness in both the fornices.


Her haemoglobin was 8.4 g%, blood group was O positive and urine routine proteinurea was present. Her liver function and renal function tests were normal and platelet count was two lakhs. Emergency ultrasound showed an extra uterine gestation of 30 weeks with fetal demise and free fluid in peritoneal cavity.

Differential diagnosis

Primigravida at 30 weeks period of gestation with abdominal pregnancy with fetal demise with eclampsia was presented, this case may be rarely confused for acute abdominal conditions, but presence of gravid uterus helps in diagnosis.


A tentative diagnosis of primigravida at 30 weeks period of gestation with abdominal pregnancy with fetal demise with eclampsia was made and patient was taken for emergency laprotomy and magnesium sulphate was continued according to Pritchard’s regimen for the treatment of eclampsia.

Intraoperatively there was haemoperitoneum of around 500 cc, dead fetus lying with intact membranes, baby extracted by breech and the placenta came along with the cord during breech extraction. There was clot of around 50 g in the peritoneal cavity and after removing the blood clot, a bicornuate uterus was seen with left horn of normal size and intact and the right horn showed rupture in the posterior aspect extending from fundus to about 8 cm below (figures 1 and 2). The ruptured horn is sutured in two layers, perfect haemostasis was achieved. There was a thick fibrous band extending between the two horns (figure 3). Peritoneal wash was given. Abdomen was closed in layers.

Post operatively two units of packed cells were transfused in the intra and immediate post operative period. Post operative recovery was uneventful. Magnesium sulphate was discontinued after 24 h and the patient was discharged on the seventh post operative day. Contraceptive advice was given and importance to continue for minimum of 2 years was explained to the patient.

Outcome and follow-up

Patient was followed up for 6 months regularly and postoperative period was uneventful. She resumed her menstrual cycles after 6 months and her menstrual cycles were regular and scan was done after 1 year after surgery which showed bicornuate uterus.


Incidence of uterine anomalies is 0.1%–3% in general population, 3.5% in infertile women and about 13% in the women with recurrent pregnancy loss. Among that bicornuate uterus constitutes 1.2%.2 Bicornuate uterus belongs to the class IV according to The American Fertility Society Classification of Mullerian anomalies (1988).3

The uterus is formed during embryogenesis by the fusion of the two paramesonephric ducts (also called Mullerian ducts). This process usually fuses the two Mullerian ducts into a single uterine body. Lack of fusion of these Mullerian ducts can lead to various types of malformations of the female genital tract.4

Uterus bicornis unicollis (bicornuate uterus), which is a common type seen represents an uterine malformation where the uterus is present as a paired organ resulting from the failure of the embryogenetic fusion of part of the Mullerian ducts. As a result there is a double uterus with a single cervix and vagina. Each uterus has a single horn linked to the ipsilateral fallopian tube that faces its ovary. The bicornuate uterus often have an unusually thick strong round ligaments and a thick vesicorectal fold running between them. Implication of uterine malformation relates inversely to the degree of fusion defect and may be associated with renal tract anomalies.5

Incidence of pregnancy in rudimentary horn is 1/40 000 pregnancies. Rupture in such cases occurs because of inability of malformed uterus to expand as a normal uterus.6 The walls of the anomalous uteri tend to become abnormally thin as pregnancies advances. Thickness can be inconsistent over different aspects of the myometrium, and the placenta does not adhere properly.7 The rupture in rudimentary horn is likely to occur in late first trimester or even in second trimester. Rarely pregnancy can go on till late second trimester before rupturing. The haemorrhage occurring because of rupture is massive and can be life-threatening, unless diagnosed and treated promptly. Ravasia et al reported an 8% incidence of uterine rupture in women with congenitally malformed uteri compared with 0.61% in those with normal uteri (p=.013) who were attempting vaginal birth after caesarean.8 Induction with prostaglandin E1 is an important risk factor associated with rupture. Pregnancies implanted in the rudimentary horn of the uterus pose special risk for those women undergoing induction of labour, with a uterine rupture rate of up to 81%, 80% of ruptures occurred before the third trimester, with 67% occurring during the second trimester. The timing of rupture can occur from fifth week onwards. Rupture is usually associated with catastrophe and bleeding is torrential and 90% of maternal deaths have been reported within 10–15 months after rupture.

Rudimentary horn pregnancy should be suspected whenever difficulty is experienced while terminating a pregnancy and every attempt should be made to rule out the same. Uterine abnormalities, though rare can be encountered in pregnancy. There is need to build capacity for making an antenatal diagnosis in order to ensure appropriate management.9

Prostaglandin E1 is a cheap drug and it is stored in room temperature, so it is often used for the induction of labour. There are no specific guidelines for induction of labour with prostaglandin E1, but American Congress of Obstetricians and Gynaecologists (ACOG) recommends use of prostaglandin E1 at lower dose (25 mcg every 3 to 6 h) for the induction of labour as level A recommendation. ACOG said that the data on the safety of high-dose misoprostol (50 mcg every 6 h) were ‘limited or inconsistent’, making its recommendation on high-dose misoprostol an evidence level ‘B’ recommendation.

Learning points

  • ▶ Bicornuate uterus belongs to the class IV according to The American Society for Reproductive Medicine Classification of Mullerian anomalies (1988) and results from failure of fusion of Mullarian ducts in the upper part.
  • ▶ Rupture in such cases occurs because of inability of malformed uterus to expand as a normal uterus. The walls of the anomalous uteri tend to become abnormally thin as pregnancies advances. Thickness can be inconsistent over different aspects of the myometrium, and the placenta does not adhere properly.
  • ▶ Rupture of anomalous uterus pregnancy should be suspected whenever difficulty is experienced while terminating a pregnancy and every attempt should be made to rule out the same particularly in unbooked cases.
  • Competing interests None.
  • Patient consent Obtained.



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Source: BMJ