Monthly Archives: October 2014

Exercise and the ‘Good’ Bugs in Our Gut

Exercise and the ‘Good’ Bugs in Our Gut

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Gretchen Reynolds on the science of fitness.

Being physically active may encourage beneficial germs to thrive in your gut, while inactivity could do the reverse, according to an innovative new study. The findings suggest that, in addition to its other health benefits, frequent exercise may influence our weight and overall health by altering the kinds of organisms that live inside of us.

In recent years, there has been an explosion of interest in the role that gut microbes play in whole-body health. A multitude of studies have shown that people with large and diverse germ populations in their digestive tracts tend to be less prone to obesity, immune problems and other health disorders than people with low microbial diversity, and that certain germs, in particular, may contribute to improved metabolic and immune health.

But little science had examined the interplay between physical activity and gut bugs in people. So, for a study published this month in Gut, researchers at University College Cork, part of the National University of Ireland, and other institutions, set out to learn more by turning to a group of people who exercise a lot: the national rugby team of Ireland.

“We chose professional athletes as a study group, because we wanted to be sure not to miss any effect of exercise and needed a group who were safely performing at the extremes of human endeavor,” said Dr. Fergus Shanahan, an author of the study who is a professor of gastroenterology and director of the Alimentary Pharmabiotic Center at University College Cork.

Forty of the players agreed to participate. At the time of the study, the men’s national team was in preseason training and the players were exercising strenuously for several hours every day.

For the sake of comparison, the researchers also recruited two groups of healthy adult men, none of them athletes. One group consisted of men with a normal body mass index. Most of the men in this group exercised occasionally but lightly.

The men in the final group were generally sedentary and had a body mass index that would qualify them as overweight or obese. This group was included, Dr. Shanahan said, because the rugby players, although supremely fit, were physically huge, with body masses well above normal. The researchers wanted to compare their gut microbes to those of men whose weight was similar, if not their musculature.

The scientists drew blood and collected stool samples from all of the men, rugby players and non-athletes alike. The volunteers also completed lengthy questionnaires about their exercise routines and diet, and spoke with a nutritionist about their typical daily food intake.

Then the scientists analyzed the men’s blood for markers of muscle damage and inflammation, which would indicate how much each volunteer had — or had not — been moving and exercising recently. The scientists also used sophisticated genetic sequencing techniques to identify and enumerate the particular microbes living in each man’s gut.

As it turned out, the internal world of the athletes was quite different from that of the men in either of the control groups. The rugby players had considerably more diversity in the make-up of their gut microbiomes, meaning that their intestinal tracts hosted a greater variety of germs than did those of the other men, especially the men in the group with the highest B.M.I.

The rugby players’ guts also harbored larger numbers of a particular bacterium, uneuphoniously named Akkermansiaceae, that has been linked in past studies with a decreased risk for obesity and systemic inflammation.

Interestingly, the rugby players’ blood showed low levels of markers for inflammation, even though the men were exercising intensely. Their muscles were being pummeled but, in physiological terms, recovering well.

The men in both of the control groups, on the other hand, especially those with the highest B.M.I.s and who rarely exercised, had relatively low numbers of Akkermansiaceae in their guts and elevated markers for inflammation in their bloodstreams.

These findings “draw attention to the possibility that exercise may have a beneficial effect on the microbiota,” Dr. Shanahan said, in ways that improve bodily health.

However, the results are still preliminary, he said. This study was small and, because of its methodology, the researchers can’t determine how exercise alters gut germs or tease out the effects of intense exercise from those of diet. The rugby players consumed far more calories than did the other men, with a much larger percentage of their diet consisting of protein. Such nutritional differences can affect which microbes thrive in the gut. The athletes also were training at a level that few of us would be able or willing to emulate.

Dr. Shanahan and his colleagues have begun a follow-up study examining whether and how moderate exercise changes the gut environment in both men and women. The results should be available later this year.

But even in advance of those findings, he said, it seems likely that any amount of exercise should make your gut more welcoming to the bacteria that you want residing there.

There’s no ‘rushing women’s syndrome’ but hormones affect mental health

20 June 2014, 2.30pm AEST

There’s no ‘rushing women’s syndrome’ but hormones affect mental health

Political controversies often use the suffix “gate“ to embellish their significance. In pop psychology, the equivalent is the made-up “syndrome”, which involves a combination of symptoms and circumstances…

Hormones are one of many factors that can trigger or perpetuate mental ill health. Sascha Kohlmann/Flickr, CC BY-SA

Political controversies often use the suffix “gate“ to embellish their significance. In pop psychology, the equivalent is the made-up “syndrome”, which involves a combination of symptoms and circumstances to explain behaviours and reactions.

The latest is “rushing women’s syndrome”, which former swimmer Lisa Curry used to explain her hormonal shifts leading to her divorce.

But while this syndrome is not a medical diagnosis, Curry is right to point out a link between hormones and mental health. Mental illnesses are due to a combination of biological, psychological and social factors. And women are twice as likely as men to experience mental illnesses such as depression and anxiety disorders.

Hormonal shifts

Women have biological hormone shifts on a cyclical basis and these hormonal shifts have been linked with mood changes. Many girls experience various mood swings and other changes in mental health around puberty, which is time of major hormonal change.

Some women who take certain types of the combined oral contraceptive experience depressive symptoms with irritability, loss of enjoyment and even suicidal thoughts. The “pill” is a great liberator of women in terms of reproductive control but the negative mental health side effects of certain types have not been well researched.

Other key hormonal mental illnesses are post-natal depression and psychosis. Soon after giving birth, there is a sudden rapid drop in the high levels of pregnancy hormones and this shift is thought to be a potent trigger for post-natal disorders.

Women experience a major hormonal shift during the transition to menopause, during which time they are 14 times more likely than usual to experience depression. This is known as perimenopausal depression. It affects women differently than other types of depression, causing anger, irritability, poor concentration, memory difficulties, low self esteem, poor sleep and weight gain.

There is a great deal of individual variation in the vulnerability to the effects of hormone shifts on mood. Timothy Krause/Flickr, CC BY

Perimenopausal depression is not well recognised and is often poorly treated with standard antidepressant therapies. Women with this type of depression generally respond better to hormone treatments. But the link between depression and hormones is not often made.

Another poorly understood condition is premenstrual dysphoric disorder (PMDD), which is a severe form of cyclical depression with its origin in hormone shifts between phases of the menstrual cycle.

It’s also important to note that trauma and violence can lead to chronically elevated levels of the stress hormone cortisol, causing significant mental ill health at any time in a woman’s life. High cortisol levels have huge impacts on many brain regions resulting in rage, suicidal thoughts, obesity, infertility and learning problems.

So, what’s going on?

The reproductive hormones estrogen, progesterone and testosterone all have key interactions with many brain chemicals and circuits. They are potent and have been shown in animal studies to acutely impact on the key emotional regulation centres as well as modulating behaviours.

Estrogen is a neuroprotective agent and has direct impacts on dopamine and serotonin, the key brain chemicals associated with the development of depression and psychosis. The fluctuation in hormones appears to be a potent trigger for mental ill health.

Our clinical studies involved giving estradiol (a potent form of estrogen) to consenting women with schizophrenia and found they had a significant improvement in their symptoms of hallucinations and delusions.

Similarly, perimenopausal depression can be assisted with hormone treatment commonly used to treat menopausal symptoms such as hot flushes.

Towards greater understanding

There is a great deal of individual variation in the vulnerability to the effects of hormone shifts on mood and behaviour. This has led some experts to discount the connection between the mind and hormones.

But people rarely experience even the most obvious physical illnesses in exactly the same way – so why should we expect uniformity in the mental health impact of hormones? Besides, hormones are one of many factors that can trigger or perpetuate mental ill health.

Discussing the hormonal impacts of mental health does not demean women, as some argue. For those affected, understanding more about the relationship between hormones and mental health allows validation, empowerment and the opportunity to get effective treatments.

Music is the soundtrack to your life – what’s on your playlist?

19 May 2014, 2.56pm AEST

Music is the soundtrack to your life – what’s on your playlist?

We all know music can move us emotionally. But how does it impact on our behaviour? That relationship’s not immediately clear. A YouTube clip was doing the rounds on social media a while ago – the music…

Music can be used as part of a ‘healthy process of self-regulation’. Sascha kohlmann

We all know music can move us emotionally. But how does it impact on our behaviour? That relationship’s not immediately clear.

A YouTube clip was doing the rounds on social media a while ago – the music from one of the most chilling scenes in the 1975 film Jaws had been quite cleverly changed. Instead of the original hair-raising theme that we all know by composer John Williams, the scene was accompanied by the delicate ballet music of Tchaikovsky.

The effect was startling. It could have been a completely different film – one about a fun-loving dolphin. It’s a good example of what an incredibly powerful mood-setter music is. So many of our favourite films just wouldn’t have the same impact without the music.

Ed Yourdon
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It’s the same outside of the cinema – a fact that has been instinctively understood by humans since written records began. In ancient China, more than 4,000 years ago, flute music was prescribed to calm an over-excited foetus.

The Egyptians also seemed to use music for therapeutic purposes at least as early as 1500 BC. Then there is the much-loved biblical tale of King Saul being soothed by the playing of David’s harp in the Old Testament.

Today, we often use music to “get into” a mood – using soft music and lyrics to set the scene for romance which, as a seduction tactic, can be quite effective. Researchers in France found that women who were exposed to love songs were more likely to respond to a request for a date than those who were in a control group and did not hear this music.

At other times, we may use a fast, up-tempo piece of music at the gym to get us working harder. Music has also been used across the centuries to pump up soldiers in the face of battle, the same energising facets of the music being drawn upon, in this context to promote aggression (see famous Wagner scene from Apocalypse Now (1979) below).

So does that mean that music can be both good and bad for you? Potentially, yes.

But music exists within a socio-cultural context and it is how the music interacts with other factors that produces a particular result.

So, at the gym it is how and why the music is framed that helps to promote its invigorating qualities for the desired work-out ends. Where it could lead to aggression, there are contextual factors that influence the way in which it’s processed and in turn how it affects us.

Recent anti-noise bans that prevented live music being played in many Australian pubs connected loud music with aggressive behaviour.

The truth is that rock music might indeed encourage patrons to move faster, be more pumped up, and perhaps drink more, be less inhibited, louder, and so manifest a whole range of behaviours than might be regarded as anti-social, leading to an aggression response. But, these are not generated from the music itself, rather in the context and the alignment of many interacting factors.

masha krasnova shabaeva
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Perhaps the most useful way to reflect on the positives of music is that it can be part of a “healthy process of self-regulation” as American music therapist Bridget Doak says and, when negative, it may be part of an “unhealthy, distress-addiction cycle”.

Researchers have found that people listen to sad music for a variety of reasons. Some may find that having a good cry while listening to a piece of music is a good way to let go of bad feelings. For others it may give them a chance to think through things that are making them feel sad in their own lives and reach a point of resolution.

But some people do not have such effective ways of making themselves feel better. People with mood disorders, for example, often engage in behaviours that can make them feel worse, and music can be a part of that behaviour.

Music can have such a powerful impact on mood. Whether or not our lives resemble a light-hearted ballet or a scene of terror in shark-infested waters may have much to do with the music that surrounds us on a daily basis.

Professor Davidson will give a public talk on the use of music in daily life at the University of Melbourne on Tuesday May 20 at 6.30pm. My Life As A Playlist (2014) by Jane Davidson and Sandra Garrido is published by UWA Publishing. You can participate in research and learn more about the interaction between music listening choices and personality here.

A Promising Pill, Not So Hard to Swallow

This pill goes down easier if you forget what is in it.

Inside the experimental capsule is human feces — strained, centrifuged and frozen. Taken for just two days, the preparation can cure a dangerous bacterial infection that has defied antibiotics and kills 14,000 Americans each year, researchers said Saturday.

If the results are replicated in larger trials, the pill, developed at Massachusetts General Hospital in Boston, promises an easier, cheaper and most likely safer alternative to an unpleasant procedure highlighted in both medical journals and on YouTube: fecal transplants.

Studies show that transplanting feces in liquid form from healthy people to patients with stubborn Clostridium difficile infections can stop the wrenching intestinal symptoms, apparently by restoring healthy gut bacteria.

But fecal transplants are not easy. The procedure requires delivery of a fecal solution via the rectum or a tube inserted through the nose. As with colonoscopies, patients must flush their bowels first.

Photo

A study found that fecal pills may be a good alternative to an unpleasant transplant procedure. Credit Hohmann Lab

Finding and screening donors is time-consuming and can delay the transplant. And the costs can be significant, certainly higher than taking a simple pill.

“Capsules are going to replace the way we’ve been doing this,” said Dr. Colleen Kelly, a gastroenterologist with the Women’s Medicine Collaborative in Providence, R.I., who was not involved in the study. Dr. Kelly performs five or six fecal transplants a month, but demand is so great she is booked through January.

“It’s so labor-intensive,” she said. “You have to find a donor, have to screen a donor. If you can just open a freezer and take out a poop pill, that’s wonderful.”

While the pills are not being marketed yet, the authors of the study, published in JAMA, are already making them available to qualified patients without requiring participation in clinical trials.

Their study was small and preliminary, but results were striking: 19 of 20 patients with C. difficile infections were cured of diarrhea and related symptoms. Most saw improvements after one two-day round of pills, the rest after two or three rounds, said Dr. Ilan Youngster, the lead investigator.

Other research teams, and at least one private company, are developing and testing fecal pills. Currently, the Food and Drug Administration effectively permits doctors to give fecal transplants to qualified patients with recurrent C. difficile infections. Pills marketed commercially would have to meet F.D.A. drug-licensing regulations.

Dr. Lawrence Brandt, an emeritus chief of gastroenterology at Montefiore Medical Center who was not involved in the study, noted that “capsules are easy to take and do not have any kind of offensive odor.” Some experts said they also hoped that pills would discourage people from potentially dangerous do-it-yourself fecal transplants, which have been featured in YouTube videos.

People have used stool from family or friends, often administering it via enema.

“I know of at least one person who did it at home and came in with a very severe infection in his bowel,” said Dr. Youngster, a pediatric infectious disease physician at Massachusetts General.

That patient, treated by a colleague, “did a home brew of stool from a 2-year-old infant.”

In their study, Dr. Youngster and colleagues recruited donors via Craigslist and screened their stool to make sure it was healthy.

The stool was mixed with saline and put through sieves to remove “the yucky stuff,” Dr. Youngster said, then centrifuged and mixed with glycerol to keep bacteria alive when frozen. It was piped into capsules, which were stored in deep-freeze and transferred to a regular freezer before patients swallowed them.

Dr. Youngster said the capsules could be stored for 250 days or longer. The capsules are clear, so “the fact that they are frozen is actually good, because then you can’t see what’s in them.”

The patients, 11 to 89 years old, had each experienced at least two episodes of C. difficile that antibiotics had failed to control. After one round of dosing (two days, 15 capsules per day), diarrhea cleared up in 14 patients. Five others, sicker than the rest beforehand, responded after a second two-day dosing about a week later. One of this group relapsed and needed another dose.

One patient may not have responded because of liver problems, Dr. Youngster said. There were no serious side effects, not even the vomiting researchers had expected. Six patients had mild cramps or bloating.

Deirdre, 37, a technology consultant in Boston, acquired C. difficile after receiving antibiotics for a breast infection and struggled with recurrences for months before learning of the study.

“At first I was kind of grossed out,” said Deirdre, who asked that her last name be withheld because of privacy concerns. But about a week after taking the capsules, which “kind of felt like small ice cubes,” her digestive system began to normalize.

“If this is a treatment that was 90 percent effective and you can get over the gross factor, it seems to be kind of a no-brainer,” she said.

Interest in fecal treatments has grown since a 2013 study found transplants are nearly twice as effective as antibiotics for recurring C. difficile. A nonprofit in Cambridge, Mass., OpenBiome, sends frozen stool samples to hospitals for fecal transplants.Pills are being tested with promising results elsewhere, and a company called Seres Health is in advanced trials of a pill incorporating certain bacteria from stool.

Dr. Alexander Khoruts, a gastroenterologist at the University of Minnesota, said some researchers were trying to freeze-dry stool samples so they could be made into powders that could be stored at room temperature.

Dr. Josbert Keller, a Dutch gastroenterologist who led last year’s fecal transplant study, said he would try capsules. “It’s much easier for the patient,” he said.

What are cancer clusters?

1 March 2014, 2.32pm AEST

Explainer: what are cancer clusters?

Most of us are living longer and we are all expected to be working longer. Because the likelihood of cancer increases as we age, we’re more likely to be diagnosed with cancer while still a member of the…

A cancer cluster generally features an unusually high number of the same type of cancer occurring in a group of people with a common exposure. Shutterstock

Most of us are living longer and we are all expected to be working longer. Because the likelihood of cancer increases as we age, we’re more likely to be diagnosed with cancer while still a member of the paid workforce.

That is equally true of our ageing workmates. An increasingly common phenomenon is that of a group of people – who might have been working in the same organisation for decades – will see their peers diagnosed with cancer around the same time.

Concerns that there may be a “cancer cluster” are sometimes raised when there is something unusual about the workplace: its location, the use of a certain types of equipment, old buildings that may contain known carcinogens such as asbestos, and so on.

Some of these factors seem to be at play in the most recent suspected cancer cluster at what is known as “the chook house” at the Victorian state Parliament.

Without knowing all the details it’s important to avoid making any specific comment on that case. But it raises an important issue: how do you differentiate between a “cancer cluster” and a normal pattern of cancer diagnoses?

A cancer cluster generally features an unusually high number of the same type of cancer occurring in a group of people with a common exposure – be it where they live, where they work or some other usually long-term exposure to an agent that has brought about the cancer.

The cancer cluster that attracted the most recent attention was the 2006 Brisbane ABC case. Of the 550 female staff, ten women were diagnosed with invasive breast cancer between 1994 and 2006 – a six-fold increase over the number of cases that might have been expected.

Governments are still working out how to deal with the enormous (but as yet unquantified) amount of asbestos in our workplaces, homes and public buildings. Shutterstock

The precise cause of those cancers remain uncertain, and the result being due to “chance” is still considered likely. The investigation did, however, lead to the building of a new ABC complex in Brisbane.

An earlier and now famous case was the Wittenoom asbestos miners and their families who have been diagnosed with a range of asbestos-related diseases, including mesothelioma, since the mine closed in the 1960s. This case helped confirm the now well-accepted link between exposure to asbestos and a number of respiratory diseases.

Uncertainty remains the most common outcome of cancer cluster investigations. A group in the United States examined the outcome of 428 cancer clusters investigations over two decades in that country and found no real increase in cancer cases above what might have been expected in 87% of “clusters”.

The study found one cluster investigation where the genuine increase in cancer cases had an identifiable cause: ship builders living in South Carolina who were exposed to asbestos through their work at a naval shipyard.

Of the other 69 suspected clusters where a substantial increase in cancer rates were observed, the cause remained unclear. In the two remaining cases, there was some indication of an (inconclusive) association between an identified exposure – contaminated water and/or air due to industrial pollution – to leukaemia.

In Australia, potential cancer cluster investigations are conducted by epidemiologists, with involvement from occupational hygienists, statisticians and occupational physicians who are independent of the employer, and are often government employees or consulting academics.

Cancer risk increases dramatically with age. Shutterstock

Half of all men and a third of all women in Australia are likely to have a cancer diagnosis by the age of 85.

While common, cancer it is also the most feared illness. It’s therefore important that an appropriate expert takes the time to listen carefully to the employees’ or residents’ concerns and any theories that might explain the phenomenon.

Cancer is not one disease but a category of disease that is made up of over 200 different illnesses with different causes, pathways and treatments. So if the suspected cluster involves lots of different types of cancer – some people effected by breast cancer, some by lung cancer, some bowel cancer and some leukaemias, for instance – then the workplace (or suburb or other exposure) is an unlikely culprit.

Likewise, if some of the people with cancer have been at that workplace or lived in that street (or had that exposure) for a short period, or had previous disease or risk factors that might explain the cancer, its unlikely to be a cluster.

After looking at the situation systematically, the employees’ or residents’ concerns may be allayed and the initial assessment concluded.

Of course, there may be legitimate grounds for concern. For example, exposure to pesticides, solvents, wood dust, diesel exhaust and radiation are established carcinogens that occur in some workplaces.

In Australia, around 5,000 cases of cancer a year are a result of occupational exposures to things such as environmental tobacco smoke, UV radiation in addition to those mentioned above.

If health authorities have cause to proceed with a formal investigation and a known carcinogen is identified, employers or landlords should act immediately to remove or reduce exposure – waiting for the final results before taking action makes no sense.

Wood dust is a cancer-causing agent. Shutterstock

Finally, it’s important to keep things in perspective. While we don’t know for sure what causes about half of all cancers, lifestyle factors are probably far more likely to be contributing to cancer risk than where we work or where we live.

We can all reduce our cancer risk by quitting or not taking up smoking, establishing and maintaining a healthy body weight, avoiding excessive UV exposure and excessive alcohol consumption, being more physically active and eating healthy food.

In broad terms Australia has a safe, well-managed environment with low levels of pollution by world standards. Constant effort is required to maintain and improve on that status.

And there is room for improvement. Like everything we do – even if we are doing okay, it makes sense to try and do even better. It’s a balancing act. But one that we will be increasingly required to face.

The myth of age-related cognitive decline

24 January 2014, 2.18pm AEST

The myth of age-related cognitive decline

The tide is changing in our understanding of old age. For a long time, behavioural scientists have thought that old age is associated with cognitive decline such as memory problems, and difficulties in…

Getting older and slower may just be the result of more experience than younger folk. Flickr/Neil. Moralee

The tide is changing in our understanding of old age. For a long time, behavioural scientists have thought that old age is associated with cognitive decline such as memory problems, and difficulties in learning and concentration.

But in this month’s Topics in Cognitive Science, linguistics researcher Michael Ramscar and collaborators demonstrate that this way of thinking may be fundamentally wrong.

Healthy ageing, Ramscar explains, may be nothing more than gaining experience, and then dealing with the consequences of having learnt from that experience:

Flickr/Carl Nenzén Lovén
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Older adults’ changing performance reflects memory search demands, which escalate as experience grows.

In other words, as people get older, they gather more experiences, they learn more names for things, and they potentially better understand how the social and economic systems around them work – and this makes them slower.

So while youth has the benefit of speed and flexibility, age has the benefit of wisdom and guile … and slowness.

The trade-off

Some of this we already know, even if we’ve never really thought about it in this context. Years of research have shown that older people have larger vocabularies than younger people, other things being equal.

In their paper, Ramscar and associates show that even this we’ve probably underestimated, because older people tend to know a lot of very low frequency words such as “zaftig” and “arroyo” and “byzantine”, words that are difficult to test because there are so many of them. Younger people tend to know fewer of these words.

Flickr/by Janine
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You can get a sense of this yourself. Have a third party pick up a dictionary and read random “rare” words to you and someone who is either older or younger than you, then see who knows more definitions for these rare words. The research suggests that the older person will know meanings of those rare words when the younger person simply has no idea.

Relating the unrelated

We also know that older people tend to do better in many decision making tasks but Ramscar and colleagues go much further. They show that knowing more has consequences in terms of speed and demonstrate this via a series of analyses involving cognitive models of learning and simple analyses of text.

Using a well-test cognitive model, they show that by simply teaching it more, they can make it slower at recognising certain things (like words). This slowness is characteristic of what many studies find in older individuals.

In another study, Ramscar and colleagues show that the learning impairments may also be due to older people knowing more.

A standard task for this is the paired-associate task. In the paired-associate task a person is asked to remember a set of word pairs, like UP-DOWN and OBEY-INCH.

Try a paired-associate task here.

If they later see OBEY, they should say INCH, for example. Older people often do more poorly overall than younger people when trying to learn many of these pairs.

However, the real signal in this data appears to be that older people are much better at learning the associated pairs, like UP-DOWN, but poorer at learning less typical pairs like OBEY-INCH.

Ramscar and colleagues show that this is predicted from the statistical structure of a lifetime of experience with text. In other words, the older individuals will over-learn common relations, but also learn that unrelated things are … well … unrelated. It’s harder for them to learn these unrelated things – they have a lifetime of experience telling them otherwise.

The message is fairly intuitive. Computers get slower as we store more information on them. Information gets harder to find in libraries for each additional book stored in that library. Libraries are vast and valuable, but they are rarely fast.

Compare that with a little bookshop. You can get in and out quickly, but you may be less likely to find what you’re looking for.

Testosterone and brain function in women

These are 2 further studies showing the benefit of testosterone to women. Search “testosterone for women” on my website for other studies showing testosterone reduces a womens risk of developing breast cancer, as well as giving women an enhanced sense of wellbeing. Of course, do not forget the boost to libido testosterone provides, which is the main reason most women take it. The best way to take testosterone is through the skin – either a cream or as a troche.
Menopause. 2014 Apr;21(4):410-4. doi: 10.1097/GME.0b013e3182a065ed.

Effects of testosterone on visuospatial function and verbal fluency in postmenopausal women: results from a functional magnetic resonance imaging pilot study.

Abstract

OBJECTIVE:

This study aims to investigate the effects of testosterone on cognitive performance during functional magnetic resonance imaging (fMRI) in healthy estrogen-treated postmenopausal women.

METHODS:

This was an open-label study in which postmenopausal women on nonoral estrogen therapy were treated with transdermal testosterone for 26 weeks. Women performed tests of verbal fluency (number of words) and mental rotation (reaction time and accuracy) during pretreatment and posttreatment fMRI. Blood oxygen level-dependent (BOLD) signal intensity was measured during fMRI tasks.

RESULTS:

Nine women with a mean (SD) age of 55.4 (3.8) years completed the study. Twenty-six weeks of testosterone therapy was associated with significant decreases in BOLD intensity during the mental rotation task in the right superior parietal, left inferior parietal, and left precuneus regions, and during the verbal fluency task in the left inferior frontal gyrus, left lingual gyrus, and medial frontal gyrus (all P < 0.05), with no change in task performance, accuracy, or speed.

CONCLUSIONS:

Testosterone therapy is associated with reduced BOLD signal activation in key anatomical areas during fMRI verbal fluency and visuospatial tasks in healthy estrogen-treated postmenopausal women. Our interpretation is that testosterone therapy facilitates preservation of cognitive function with less neuronal recruitment.

Clin Endocrinol (Oxf). 2014 Apr 9. doi: 10.1111/cen.12459. [Epub ahead of print]

Transdermal Testosterone Improves Verbal Learning and Memory in Postmenopausal Women Not on Estrogen therapy.

Abstract

OBJECTIVE:

The aim of this study was to examine the effects of testosterone on verbal learning and memory in postmenopausal women.

DESIGN:

Randomised placebo-controlled trial in which participants were randomized (1:1) to transdermal testosterone gel 300mcg/ day, or identical placebo, for 26 weeks.

PATIENTS:

92 post-menopausal women aged 55-65 years, on no systemic sex hormone therapy.

MEASUREMENTS:

The primary outcome was the score for the International Shopping List Task (ISLT) of CogState. Secondary outcomes included other CogState domains, the Psychological General Well-Being Index (PGWB) and safety variables.

RESULTS:

89 women, median age 60 years, were included in the primary analysis. Testosterone treatment resulted in statistically significantly better performance for the ISLT (improved verbal learning and memory) compared with placebo, adjusted for age and baseline score (mean difference 1·57; 95%CI 0·13, 3·01) p=0.03). There were no significant differences for other CogState domains or the PGWB scores. At 26 weeks, the median total testosterone was 1·7 nmol/L (interquartile range (IQR) 1·1, 2·4) in the testosterone group and 0·4nmol/L (IQR 0·3, 0·5) in the placebo group.

CONCLUSIONS:

The small but statistically significant effect of testosterone treatment on verbal learning and memory in postmenopausal women provides the basis for further clinical trials.

This article is protected by copyright. All rights reserved.

KEYWORDS:

Testosterone, postmenopausal women, verbal learning

The Unworried Unwell

The Unworried Unwell

By ABIGAIL ZUGER, M.D.
Leif Parsons

Dr. Abigail Zuger on the everyday ethical issues doctors face.

She is an organized, punctual patient who makes appointments and keeps them. He drops in whenever he feels like it. Her visits are short and organized; his seem to drag on forever. The two have nothing in common — except that they both leave the office empty-handed.

Most people leave a medical encounter with something to show for it, whether tangible (prescriptions, referrals) or ephemeral (good advice). These two patients accept nothing, especially not the advice.

They both feel fine, although neither could be called well. For her, the problem is blood pressure, with readings so far into the “malignant” zone that we compulsively recheck her with different cuffs, trying to blame the equipment.

No such luck: Her results are permanently stroke-making, kidney-ruining, eyesight-threatening. She declines any form of medication. At first, we figured she was just politely taking her business elsewhere, but no, she keeps coming back. “Just want to see how I’m doing,” she says. She is always doing the same.

His problem is a rapidly accelerating H.I.V. infection. His blood tests are as alarming as her blood pressure, and as suggestive of imminent catastrophe, but he has no interest in any of the ways we propose to avert it. “Just want to see how I’m doing,” he says every few months as he saunters away, lab report tucked into his pocket.

There aren’t many medical situations where doctors’ imaginations trump those of their patients. In fact, when it comes to chronic illness, doctors are notoriously shortsighted, seldom perceiving the seismic effects pain and disability can exert on all aspects of a patient’s personality and family life. The medical problems may be clear, but their context often remains obscure.

For people who feel fine, though, the situation can be just the reverse: It is the patient with feet of stone firmly planted in the here and now, while medical personnel spin wild tales of coming catastrophe, full of verbs conjugated in the future probable.

Some people see our visions even more clearly than we do, accepting all offered preventives and asking for more. Most of the rest take our word for it and resignedly go along with the program. A few say thanks but no thanks, and saunter away.

And it is that last little group — including him with his virus and her with her blood pressure — who hold the key to the way future generations of doctors will be practicing medicine.

Medical care is all about prevention these days: locating and disarming invisible swords of Damocles before they drop. In the process, of course, we are creating whole lists of “pre-illnesses,” situations likely to lead to actual illness over time — or, in the case of “prehypertension” (blood pressure that is almost too high), situations likely to lead to situations likely to lead to illness. People who opt to have their DNA analyzed by a commercial lab see their future spelled out in the vaguest possible terms: the risks of various diseases compared to the average.

Soon, it seems, we will do little but talk to our pre-patients about all their various pre-diseases. And we still have exactly no idea how best to conduct those conversations.

There is the reasoned numerical approach (“30 percent of people with your problem of X will develop Y”). Many studies (and all casinos and lotteries) illustrate how abysmal is the average person’s understanding of risk when couched in mathematical terms.

There is the in-your-face approach, like the one taken by a series of antismoking advertisements featuring harsh close-ups of painfully moribund smokers. No one likes those. “Couldn’t get the TV off fast enough,” said one smoker I know.

There is the blunt “it’s your funeral” approach: doctors who indicate by word or deed that they have no time for you till you are ready to knuckle under and behave the way a pre-patient should.

And there is the fallback “beat your head against the wall” approach, with the same dire predictions enunciated over and over again, a millstone ground by a plodding ox. This particular routine enervates doctor and patient alike: The future probable is a pretty dull tense, summoning none of the adrenaline that attends acute fix-it-up care.

Sometimes we forget, though, that medicine is fundamentally all about the thankless art of prognosis, a practice only a few little data-filled footnotes away from prophecy. In fact, our future of treating pre-illness will simply catapult us right back to a priestly past, as we offer up misty visions of the future and encourage the masses to see with us and act accordingly.

We have said many things over the centuries to those who, for whatever reason, cannot see what we see. Of them, I suspect that by far the best, most effective and most important has always been “See you next time.”

Exam guide: what to eat to help your brain

Although this is not much to do with hormones and health, many of you may have children and grandchildren writing exams at the moment, who may find this useful. Of course, I have many mature age students, some of them meno0pausal, who have gone back to uni. This may be useful.
7 October 2014, 6.35am AEDT

HSC exam guide: what to eat to help your brain

Exam time is quickly approaching for HSC and university students. While study is at the forefront, nutrition is often the furthest thing from students’ minds. However, a healthy diet plays a vital role…

Certain foods can help your brain retain information. Shutterstock

Exam time is quickly approaching for HSC and university students. While study is at the forefront, nutrition is often the furthest thing from students’ minds. However, a healthy diet plays a vital role in attaining optimal academic performance during the rigours and challenges of exam time.

Key foods and their components have been found to enhance cognitive function, improve mental alertness and enable sustained concentration to help students learn and remember the themes, concepts or formulas for their final exam.

Protein and brain power

Protein consumed from food sources provide the body with amino acids, or the building blocks, to produce key chemicals, such as neurotransmitters for the brain. Neurotransmitters are vital for brain cell-to-cell communication. Key neurotransmitters in terms of improved cognitive function and brain health include serotonin, norepinephrine and dopamine.

Protein helps with memory, learning and mood. Shutterstock
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Serotonin, produced from the amino acid tryptophan, is found in brown rice, cottage cheese, salmon, red meat, carrots, peanuts and sesame seeds. It helps in the regulation of memory, learning and mood.

The amino acid tyrosine is involved in the production of the neurotransmitters norepinephrine, key to the transfer of memories to long-term storage, and dopamine, which is involved with improving motivation and activity. Tyrosine-rich foods include avocados, turkey, chicken, red meat, dairy, lentils, lima beans and sesame seeds.

The consumption of foods low in these amino acids, such as many “junk” foods, will result in low levels of serotonin, dopamine and epinephrine. This leaves students with lowered mood, concentration levels and a reduced ability to transfer learning to long-term memory. Similarly, consuming alcohol, caffeine and foods high in refined sugar will lower neurotransmitter levels such as dopamine, resulting in decreased motivation, mental dullness and an inability to focus.

Carbohydrates for sustained energy

Carbohydrates can provide sustained energy for mental alertness and concentration for those long study periods and for three-hour-plus exams. Glucose, the energy storage form of carbohydrates in the body, is the primary source of energy used by the brain. To ensure energy is sustained, students need to be careful which type of carbohydrates they are consuming.

Switching from white bread to multigrain is an easy way to sustain energy. Shutterstock
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There are two primary forms of carbohydrates, complex carbohydrates and simple carbohydrates. Complex carbohydrates are found in wholegrain cereals, breads, pastas, fruits and vegetables. Simple carbohydrates, as their name suggests, comprise single carbohydrate units such as glucose or fructose and are found in lollies, muesli bars, energy bars and drinks, and soft drink.

In the body, complex carbohydrates are absorbed a lot more slowly. The slower absorption rate means that energy is slowly released and available for a longer time. This allows students to be more alert, able to concentrate and commit information to memory for longer and more effectively.

Sugar burn-out

Sugar burn-out refers to the impending “high” and subsequent “crash” after consuming foods containing high levels of simple or refined carbohydrates.

Too much sugar = bad for brain Shutterstock
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As the sugar from these foods is quickly absorbed by the body there is a rush of glucose into the bloodstream, creating a short burst of energy, a “high”. The body (and brain) quickly use up this energy and the high is just as quickly followed by a burn-out or “crash”, leaving the person feeling lethargic, irritable and sleepy. Learning is not committed to memory and come exam time information cannot be effectively recalled.

Sustaining nutrition for a long exam

To ensure students have energy for that exam of three hours or more, they should eat a light meal comprising carbohydrates and protein – for example, baked beans on wholemeal toast or an egg or tuna salad wholemeal sandwich – one to two hours beforehand.

Even if you’ve been unhealthy all year, starting now will still help. Shutterstock
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If the student is nervous, then they should try a snack of vegetable sticks and hummus or wholemeal raisin toast around one hour beforehand. This way their body and brain will be fuelled to go. In terms of fluids, water is best.

Brain function is influenced by short-term and long-term dietary changes. For overall health and optimum academic performance it is better to consume a healthy diet comprising a mix of fruits, vegetables, meats, cereals and dairy over the longer term. If nutrition has not been a primary focus over the last couple of months, then making dietary improvements now can help towards students achieving academic goals.

Remember the healthier the food, the more effective your brain is at retaining information and the better you’ll perform come exam time.


This is part of The Conversation’s Exam Guide

When Doctors Make Errors


When Medical Students Make Errors

“I’m sorry. I messed up.”

Those words are hard enough to say when you’ve missed a meeting or forgotten a friend’s birthday. When the stakes are as high as a patient’s life or death, or mean the difference between spending an evening at home with family and friends or a night in the hospital listening to alarms and getting blood draws, they can be downright paralyzing. Yet doctors must speak some variation of those words in hospitals across the country every day.

Dhruv Khullar

A few years ago, I admitted a young woman who came to the emergency department vomiting and feverish. For several days, she’d had pain when she urinated and aching on her side when she moved — textbook symptoms of a urinary tract infection that had migrated to the kidneys. So we started her on intravenous fluids and tobramycin, a potent antibiotic with potent side effects. Later we learned she had already received a dose in the E.R. — worrisome because tobramycin’s risk of harming the kidneys increases with accumulated doses.

Fortunately, there was no kidney damage, and the patient soon left the hospital fully recovered. She later said she wished she hadn’t known about the double dose. It hadn’t caused her any harm, and added to the anxiety of an already frightening hospital stay.

I think, and research suggests, that most patients would like to know — and know early — if an error has occurred. But my patient’s response highlights the complexity of the issue.

The Institute of Medicine’s 1999 landmark report “To Err Is Human” found that as many as 98,000 deaths occur each year because of medical errors, making them the fifth most common cause of death in the United States. Despite substantial quality improvement efforts since, medical errors remain widespread.

In 2010, the Department of Health and Human Services found that one in seven Medicare beneficiaries experiences an “adverse event” during a hospital stay, half of which are clearly or likely preventable. While an adverse event, which might include a side effect from a drug, is not always a medical error, harm can still ensue. But most such events result in minor or temporary harm; errors that end up in the news, like operating on the wrong patient or body part, are exceedingly rare.

What has become increasingly clear is that talking about medical errors with patients is important. One study at the University of Michigan found that after instituting a policy to improve transparency and open disclosure of medical errors, there were fewer lawsuits, lower liability costs and quicker resolution of claims. Other work generally supports the idea that prompt disclosure and genuine apology reduce the likelihood of legal action. It seems that ethically, legally and financially, it pays to be candid about medical mistakes.

There’s little debate about whether to disclose serious medical errors. But what about minor errors with minimal harm, or technical errors with no clinical consequences? And should errors be disclosed as soon as they occur, or after the causes and consequences are fully understood?

A colleague recently relayed the story of an elderly man he admitted with pneumonia. The man was started on an antibiotic that increased the effect of the blood-thinning medication he had been taking. When the patient woke up slurring his words and unable to move half his body, his family became alarmed. Was his stroke the result of a medical error, a drug interaction that led to excessive blood thinning and bleeding into the brain? It appeared so. But a CT scan revealed that the patient’s stroke was not the result of a bleed, but a clot — the risk of which was the reason he was on blood thinners to begin with. Yes, the patient’s blood was too thin, and yes, he had a stroke. But the former did not cause the latter.

Research suggests that patients and doctors hold very different views about what exactly should be disclosed and how it should be done. Patients want disclosure of all harmful errors, as well as why the error happened, how its consequences will be mitigated, and how similar errors will be prevented in the future. They define medical error broadly — as deviations from standards of care, adverse events and poor service. After an error, they want emotional support from physicians and an explicit apology.

Doctors define errors more narrowly: as significant deviations from accepted standards of care. They refrain from talking about “near misses” and choose their words carefully. They often avoid discussing why the error happened or how recurrences will be prevented, and some worry that an apology might increase the chances of lawsuits, even though research suggests the opposite. They, too, are greatly upset by medical errors, but are unsure about where to find emotional support.

The difficulty of disclosing medical errors is especially acute for medical trainees, who are less sure of their skills and more worried about evaluations and damaging their reputations than seasoned physicians. More than three-quarters of fourth-year medical students and almost all residents report being personally involved in a medical error. But only one-third of them report receiving formal instruction in error disclosure, though over 90 percent express interest in such training.

As a result, many trainees do not feel confident disclosing medical errors, and their attitudes about doing so vary widely. In a recent study that asked medical students and residents whether they would disclose serious errors, 43 percent said they “definitely” would, 47 percent said they “probably” would, and the remainder indicated they would do so only if asked by the patient. It is notable that trainees who had been taught how to disclose medical errors were more willing to do so.

The study also found that as trainees advance, they become more likely to disclose an error but less likely to apologize explicitly for an error or discuss how recurrences could be prevented — two components that patients feel are important for complete error disclosure. A sincere apology and an error prevention plan may offer doctors an opportunity to convert an unfortunate event into a productive conversation, potentially even strengthening the trust between doctor and patient. This approach may also reduce the incidence of lawsuits, as many patients cite insensitivity and a desire to prevent similar errors as motivating factors for legal action.

Unfortunate as it is, medical errors are an inevitable part of medicine. Even the most intelligent, capable and diligent doctors make mistakes. But it is important that they are trained to talk about those mistakes, just as they are trained to deliver bad news, obtain informed consent, or take a respectful sexual history. We must do all we can to honor the ancient creed, “First, do no harm” — but we should also learn to talk about it when we do.

Dhruv Khullar is an incoming medical resident at the Massachusetts General Hospital and Harvard Medical School. Follow him on Twitter: @DhruvKhullar.