Two UK researchers who developed a mathematical model to investigate why men appear to be the weaker sex where disease is concerned suggest there may be good reasons behind the “man flu” of popular imagination: it could be the result of evolution where ability to pursue adventure and be competitive has given them greater survival advantage than building immunity to disease.

Previous studies have shown that men tend to be more exposed to infection risk than women and when they become infected their symptoms tend to be more severe and longer lasting: this has probably led to the so-called “man flu” myth.

But as Restif and Amos point out, it doesn’t make sense: why would men evolve lower immunity if they are more often exposed to infection? Surely common sense tells us that more exposure translates into more opportunity for the immune system to develop counter-measures?

So they developed a mathematical model showing why differences between male and female responses to infection may have evolved.

According to the Royal Society, this is the first such model to take an “ecological” approach to the way infectious agents or pathogens “and their hosts interact by accounting for the effect that immunity has on pathogens and vice-versa”.

The authors also point out that previous models have tended not to take into account the dynamic relationship between host and pathogens and consider this a serious omission because the level of pathogens in the environment will clearly affect the benefits of immunity.

“… a point often overlooked is that the benefits of immunity, and possibly the costs, depend not only on the host genotype but also on the presence and the phenotype of pathogens,” write the authors, who to address this issue developed an “adaptive dynamic model that includes host-pathogen population dynamics and host sexual reproduction”.

They also fed into the model various documented characteristics of males and females, including the extent of risk taking behaviour (men are more adventure seeking), and hormonal differences.

The result showed that while the more adventurous lifestyle of males means that they are more exposed to infection, it also, paradoxically, leads to them having lower immunity.

According to a report in the Telegraph, Restif told the press that:

“An increase in male susceptibility or exposure to infection favours the spread of the pathogen in the whole population and therefore tends to select for higher resistance or tolerance in both sexes if the cost of immunity is essential.”

But, and here is where the model reveals the apparent departure from common sense, “above a certain level of exposure”, said Restif, “the benefit of rapid recovery in males decreases owing to constant reinfection”.

Even men with strong immune systems that clear infection will become reinfected quickly, so the benefit of immunity is low in comparison to the cost.

“This selects for lower resistance in males, ultimately leading to the counterintuitive situation where males with higher susceptibility or exposure to infection than females evolve lower immunocompetence,” he added.

In other words, what the model appears to be saying is that in evolutionary terms, it is more important for men to maintain the ability to mate than to recover from illness, whereas in women it is the other way around.

Restif and Amos suggest that currently their model only deals with diseases that pass directly from host to host, but it could be adapted to deal with sexually transmitted diseases and “vertical transmission” from mother to offspring. This could lead to valuable insights into how viruses spread, for instance in HIV and other areas:

“We believe our framework will prove both versatile and flexible enough to be used in a range of future studies on sexual host species,” they commented.

“The evolution of sex-specific immune defences.”

In 2009, approximately 40 percent of adults were single, according to the U.S. Census Bureau. In a new study, “I’m a Loser, I’m Not Married, Let’s Just All Look at Me,” a University of Missouri researcher examined the familial and societal messages given to women who are not married by their mid-30′s. Although the number of single women has increased, the stigma associated with being single at that age has not diminished, according to the women in this study.

“We found that never-married women’s social environments are characterized by pressure to conform to the conventional life pathway,” said Larry Ganong, co-chair of Human Development and Family Studies in the College of Human Environmental Sciences. “This pressure was manifested in women feeling highly visible and invisible. Heightened visibility came from feelings of exposure and invisibility came from assumptions made by others.”

Ganong and Elizabeth Sharp, associate professor in the Department of Human Development and Family Studies at Texas Tech University, conducted 32 interviews with middle-class, never-married women who felt that considerable attention was directed at them because of their age and single status. They felt heightened visibility in situations such as bouquet tosses at weddings. These events brought about unwanted, intrusive questions. Feeling invisible, on the other hand, was likely when others made assumptions that they were married and had children or when they had to justify their singlehood. These interactions made them feel that their actual lives weren’t important or went unnoticed.

Specifically, single women’s social worlds include:
Awareness of shifting reality as they become older; for example, the shrinking pool of eligible men and increased pregnancy risks.

Reminders that they are on different life paths than most women when others inquire about their single status and during events, including social gatherings and weddings.

Feelings of insecurity and displacement in their families of origin when parents and siblings remark about their singlehood and make jokes or rude comments.
The visibility and invisibility factors were impacted by age, according to Ganong. The mid-20′s through mid-30′s is a time of intense contemplation and concern for single women regarding their future family trajectories. Women older than 35 tend to be content with being single and don’t express as much dissatisfaction as do younger women. Women ages 25-35 felt the most stigma, which may be attributed to the fact that being single is more acceptable before age 25. After reaching that age, they feel more scrutinized by friends, family members and others.

“Mainstream media also enforce these ideas,” Ganong said. “For example, shows like ‘Sex and the City,’ which portray female protagonists who are hyper-focused on finding men, and end with the majority of those characters getting married, are popular.”

According to the Journal of Sexual Medicine, people who engage in regular sexual activity gain several health benefits, such as longer lives, healthier hearts, lower blood pressure, and lower risk of breast cancer. However, approximately 33 percent of women may not receive these benefits due to low sexual desire. Also, the marriages of women with low sexual desire may also be at risk, given a recent statistic that 25 percent of divorce is due to sexual dissatisfaction.

Some doctors are prescribing testosterone patches for women with low sexual desire. However, research shows that testosterone patches might increase the risk of breast cancer when used for just a year. Researchers are currently testing a new drug, flibanserin, which was developed as an antidepressant and affects neurotransmitters in the brain, to treat women with low sexual desire. However, experts are concerned about the side effects of this possible treatment. Now, a University of Missouri researcher has found evidence that a low-cost, risk-free psychological treatment is effective and may be a better alternative to drugs that have adverse side effects.

“Low sexual desire is the number one problem women bring to sex therapists,” said Laurie Mintz, associate professor of educational, school and counseling psychology in the MU College of Education. “Drugs to treat low sexual desire may take the focus away from the most common culprits of diminished desire in women, including lack of information on how our own bodies work, body image issues, relationship issues and a stressful lifestyle. Indeed, research demonstrates that relationship issues are far more important in predicting women’s sexual desire than are hormone levels. Before women seek medical treatments, they should consider psychological treatment.”

Mintz has authored a book based on this premise. In her book, Mintz suggests a six-step psycho-educational and cognitive-behavioral treatment approach that she based on scientific literature and more than 20 years of clinical knowledge. The treatment plan includes chapters about one’s thoughts about sex, how to talk with your partner, the importance of spending time together, ways to touch each other in both erotic and non-erotic ways, how to make time for sex and different ways to make sexual activity exciting and thus, increase women’s sexual desire.

In a study demonstrating the effectiveness of her treatment, Mintz recruited married women between the ages of 28 to 65, who said they were uninterested in sexual activity. All the women were employed and a majority had children. All participants completed an online survey that measured sexual desire and sexual functioning. Then half of the participants were selected randomly to read her book and perform the exercises outlined in her book. After six weeks, they were emailed the same survey again. The control group did not read the book. Mintz found that the intervention group who read the book made significant gains in sexual desire and sexual functioning, compared to the control group who did not read the book. On average, women who read the book increased their level of sexual desire by almost 30 percent.

“This finding is especially exciting because low sexual desire among women has been not only the most common, but the least successfully treated of all the sexual problems brought to therapists” Mintz said. “Also, although other books have been written on the topic, this is the first to be tested for its effectiveness. In addition, unlike medical treatments such as testosterone, there are certainly no known negative medical side effects associated with the treatment strategies in my book.”

Normal-weight women who drink a light to moderate amount of alcohol appear to gain less weight and have a lower risk of becoming overweight and obese than non-drinkers, according to a report in the March 8 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

More than half of American adults drink alcoholic beverages, according to background information in the article. Alcohol contains about 7 calories per gram (with approximately 28 grams per ounce) and alcohol drinking may possibly lead to weight gain through an imbalance of energy consumed and energy burned. However, research has not consistently provided evidence that consuming alcohol is a risk factor for obesity.

Lu Wang, M.D., Ph.D., of Brigham and Women’s Hospital, Boston, and colleagues studied 19,220 U.S. women age 39 or older who had a body mass index (BMI) in the range classified as normal (18.5 to 25). On an initial questionnaire, participants reported how many alcoholic beverages they typically drank per day. A total of 7,346 (38.2 percent) reported drinking no alcohol; 6,312 (32.8 percent) drank less than 5 grams; 3,865 (20.1 percent) drank 5 to less than 15 grams; 1,129 (5.9 percent) drank 15 to less than 30 grams; and 568 (3 percent) drank 30 grams per day or more.

Over an average of 13 years of follow-up, women on average gained weight progressively. Women who did not drink alcohol at all gained the most weight, with weight gain decreasing as alcohol intake increased. A total of 7,942 (41.3 percent) women who initially had normal weight become overweight or obese (BMI of 25 or higher), including 732 (3.8 percent) who become obese (BMI of 30 or higher). Compared with women who did not drink at all, those who consumed some but less than 40 grams per day of alcohol were less likely to become overweight or obese. Women who drank 15 to less than 30 grams per day had the lowest risk, which was almost 30 percent lower than that of non-drinkers.

“An inverse association between alcohol intake and risk of becoming overweight or obese was noted for all four types of alcoholic beverages [red wine, white wine, beer and liquor], with the strongest association found for red wine and a weak yet significant association for white wine after multivariate adjustment,” the authors write.

The authors caution that, given potential medical and psychosocial problems related to drinking alcohol, its beneficial and adverse effects for each individual must be considered before making any recommendation about its use. “Further investigations are warranted to elucidate the role of alcohol intake and alcohol metabolism in energy balance and to identify behavioral, physiological and genetic factors that may modify the alcohol effects,” they conclude.

A new study from the US found that normal weight women in their 40s and older who drank a light to moderate amount of alcohol gained less weight and had a lower risk of becoming obese and overweight compared to their non-drinking counterparts.

The researchers, from the Brigham and Women’s Hospital, and the Harvard School of Public Health in Boston, Massachusetts, have written about their study in a paper published online in the 8 March issue of Archives of Internal Medicine.

At 7 calories per gram (equivalent to 199 calories per ounce), alcohol is potentially a significant source of dietary calories, and more than half of adult Americans are alcohol drinkers. Meanwhile obesity is approaching epidemic proportions in the US, yet evidence on the extent to which alcohol consumption contributes to this public health crisis is patchy, suggested the authors.

For their prospective cohort study, which was sponsored by grants from the National Institutes of Health, lead author Dr Lu Wang, of Brigham and Women’s Hospital, and colleagues examined data from 19,220 women living in the US who were aged 39 and over, had no traces of cardiovascular disease, cancer, or diabetes, and whose body mass index (BMI) was in the range classified as normal (18.5 to less than 25). BMI is calculated as weight in kilograms divided by height in meters squared.

At the start of the study the women filled in a questionnaire that asked them about their daily alcohol consumption. After that they filled in questionnaires about their weight every year for an average of 13 years.

The results showed that:

* At the start of the study, 38.2 per cent reported drinking no alcohol, 32.8 per cent reported drinking less than 5 grams a day, 20.1 per cent reported drinking 5 to less than 15 grams, 5.9 per cent reported drinking 15 to less than 30 grams, and 3 per cent reported drinking 30 or more grams of alcohol a day.

* Over the 13 years of follow up, the women’s average weight went up steadily.

* 41.3 per cent of the women became overweight (BMI of 25 or more), and 3.8 per cent became obese (BMI of 30 or more).

* After adjusting for potential confounders like baseline BMI, smoking, other calorie sources, exercise, and other lifestyle and dietary factors, there was an inverse association between the amount of daily alcohol the women said they drank in their initial questionnaires and the weight gained over the follow up.

* Compared with women who did not drink at all, those who consumed some but less than 40 grams of alcohol a day had a lower risk of becoming overweight or obese.

* Women who drank 15 to less than 30 grams of alcohol per day had the lowest risk, which was nearly 30 percent lower than that of their non-drinking counterparts.

The authors also looked at four types of alcoholic beverages and found the links to be the same for all, with perhaps the strongest being for red wine.

They concluded that:

“Compared with nondrinkers, initially normal-weight women who consumed a light to moderate amount of alcohol gained less weight and had a lower risk of becoming overweight and/or obese during 12.9 years of follow-up.”

However, the authors stressed that given the potential medical and psychosocial problems of alcohol consumption, recommendations about its use should be made on an individual by individual basis.

They also suggested more studies are needed to find out the biological mechanisms of the role played by alcohol in energy metabolism, and whether any physiological and genetic factors are involved.

“Alcohol Consumption, Weight Gain, and Risk of Becoming Overweight in Middle-aged and Older Women.”

Two articles published Online First in The Lancet report that community support groups can reduce neonatal mortality. In addition, they can lower rates of maternal depression, provided that the population coverage is wide enough and the programs are suitably designed.

In trials in Nepal, participatory women’s groups have shown promise. Neonatal mortality was reduced by about one-third. Two research teams undertook to test this approach further. They carried out cluster-randomized controlled trials that were led by Anthony Costello, University College London Centre for International Health and Development, Institute of Child Health, London, UK.

Prasanta Tripathy, Ekjut, Chakradharpur, Jharkand, India and colleagues explain their work in the first article. They assigned clusters in a population of 228,186 people in Jharkand and Orissa in eastern India to either participating in women’s groups focusing on the reduction of maternal and newborn health problems, or not. A total of 19,030 births were monitored over 3 years. They found that neonatal mortality was 32 percent lower overall. It was 45 percent lower in years 2 and 3 for women who had been living in areas where women’s groups existed than for those who had not. Moderate maternal depression had fallen by 57 percent by the third year.

The authors explain: “Women’s groups led by peer facilitators reduced neonatal mortality rates and moderate maternal depression at low cost in largely tribal, rural populations of eastern India. The most likely mechanism of mortality reduction was through improved hygiene and care practices.”

They write in conclusion: “Participatory groups have the advantage of helping the poorest, being scalable at low cost, and producing potentially wide-ranging and long-lasting effects. By addressing critical consciousness, groups have the potential to create improved capability in communities to deal with the health and development difficulties arising from poverty and social inequalities.”

Professor Kishwar Azad, Perinatal Care Project, Diabetic Association of Bangladesh, Dhaka, Bangladesh and colleagues describe their work in a second article. They monitored neonatal mortality for 36,113 births over 3 years in a population of 503,163. As with Tripathy et al’s study, the study population was divided into clusters. Some of which were assigned to support from women’s groups. Findings indicate that the community support made no difference to neonatal mortality rates.

They comment: “For participatory women’s groups to have a significant effect on neonatal mortality in rural Bangladesh, detailed attention to programme design and contextual factors, enhanced population coverage, and increased enrolment of newly pregnant women might be needed.”

They note: “Women’s groups, if scaled to an adequate coverage, have the potential to reach the poorest people and bring about substantial health and non-health benefits. Nonetheless, a women’s group approach requires adequate human resources support for community mobilisation and appropriate coverage.”

“Effect of scaling up women’s groups on birth outcomes in three rural districts in Bangladesh: a cluster-randomised controlled trial”

In newborn mice, at least, mother’s milk appears to have some rather immediate and potentially far-reaching metabolic consequences. The milk intake kick-starts the liver to produce a molecule that then turns on heat-generating brown fat.

“A key phenomenon required after birth is to adapt the body to a lower environmental temperature with respect to that experienced when the fetus is inside the mother’s womb,” said Francesc Villarroya of the University of Barcelona. “We find that a key inducer of heat production in neonates is FGF21, released by the liver in response to the initiation of suckling.”

FGF21 (short for fibroblast growth factor 21) has recently emerged as a novel regulator of metabolism, Villarroya explained. Scientists knew that FGF21 is produced primarily in the liver, where it is induced after fasting in adult rodents and humans. FGF21 can also correct metabolic disorders of obese and diabetic mice.

In the new study, the researchers wanted to know whether FGF21 also has a role in metabolic shifts as newborn animals transition to life in the world. It appears that it does.

Plasma FGF21 levels and FGF21 gene expression in the liver rise dramatically after birth in mice, the researchers report. That increase is initiated by suckling and depends on the intake of lipid-rich milk. When the researchers mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, they found that the treatment enhanced the expression of genes involved in heat generation, or thermogenesis, within brown fat, to increase body temperature. Brown fat cells treated with FGF21 showed increased expression of thermogenesis genes. The cells also expended more energy and burned more glucose.

Villarroya’s team thinks what happens in those first hours of life may have consequences for the individual that carry over into adulthood, noting that FGF21 is a powerful antidiabetic agent.

“There are many evidences that alterations of dietary, genetic, environmental, or other origin in the metabolic performance during the fetal and early neonatal life can make an individual prone to develop diabetes and obesity in adulthood,” he said. “The precise mechanisms by which this happens are not fully understood. We observe that a ‘natural’ event in the postnatal life is a burst in FGF21 levels in response to suckling. It will be important to know whether any disturbance in the intensity of this naturally occurring event may have negative consequences in adulthood.”

Villarroya said that there has been something of a revolution in thinking about brown fat in recent years. That’s because scientists have found active brown fat in adult humans and have reported evidence that greater activity within brown fat can lend an individual greater resistance to obesity.

He says he suspects the pathways observed in neonatal mice do play similar roles in newborn humans, and maybe in adults, too. “It remains to be demonstrated if FGF21 is also an activator of brown fat in adult humans, but this would be of utmost importance for studies on complex metabolic diseases in adult humans,” he says.

A study published on bmj.com today reports that the longer women wait for radiotherapy after breast cancer surgery, the more chance there is of local recurrence.

Starting radiotherapy as soon as possible will minimize this risk according to the authors.

The reasonable generally accepted interval between cancer surgery and radiotherapy is four to six weeks. Evidence on the effect of waiting times in patients with breast cancer is unclear.

In order to find out more, researchers from the United States, Canada and Japan investigated the link between interval to radiotherapy and recurrence of breast cancer.

A total of 18,050 national cancer records were analyzed. The data were from women aged 65 or older who were diagnosed with early stage breast cancer during 1991-2002. All women received breast conserving surgery and radiotherapy, but not chemotherapy.

Data from the 2000 US population census was used to identify demographic information. Women were monitored for an average of five years.

The findings indicated that starting radiotherapy more than six weeks after surgery was linked to a modest but significant increase in local recurrence. In the study, more than one in four women (30 percent) started radiotherapy after this time. A total of 734 (4 percent) experienced a local recurrence at five years.

Additional investigation showed a continuous relation between time to radiotherapy and local recurrence. This suggests that initiating radiation therapy as soon as possible could minimize local recurrence risk.

Longer periods before undergoing radiotherapy were also found among Black and Hispanic women and among women who lived outside the southern states of the US. The rates of breast conserving surgery were higher, suggesting limitations in capacity of radiation delivery.

The continuous relationship between the start of radiotherapy and local recurrence suggests that there is no “secure” threshold in terms of waiting time. Therefore, the authors recommend that radiotherapy should be started as soon as possible.

The researchers comment that the cost of increasing capacity to consistently ensure short waiting times could be important. This would need to be evaluated in return with the small absolute benefit in local recurrence. The authors conclude that it appears appropriate to consider this is a price to pay, given the recognized negative impact of local recurrence on overall survival, and the large numbers of women treated with radiotherapy for breast cancer.

In an associated editorial, Ruth Jack and Lars Holmberg from King’s College London say that minimizing delay improves outcomes; therefore investment and planning are needed.

They comment that healthcare providers need to evaluate where probable delays are occurring. Then they should make certain that these are reduced. In addition, they should ensure equal opportunities in accessing good care. On the other hand, they point out that if significant investment is required, the modest effects seen in this study would have to be weighed against other opportunities and priorities in cancer care.

“Impact of interval from breast conserving surgery to radiotherapy on local recurrence in older women with breast cancer: retrospective cohort analysis”

New research shows women who don’t receive a clot-busting drug after a stroke fare worse than men who are not treated. The study is published in the March 2, 2010, print issue of Neurology®, the medical journal of the American Academy of Neurology.

“Women need to be treated for stroke as soon as possible,” said study author Michael D. Hill, MD, MSc, FRCPC, with the University of Calgary in Alberta, Canada. “We found that women who weren’t treated had a worse quality of life after stroke than men. However, the good news is that women who were treated responded just as well as men to the treatment.”

For the study, scientists examined information from a stroke database on 2,113 people who had experienced a stroke. Of those, 232 were treated with the clot-busting drug known as tissue plasminogen activator (tPA) and 44 percent were women. Men and women were separately placed in groups based on whether they received tPA within three hours after their stroke. After six months, the people were interviewed by phone about their ability to function and quality of life.

The study found that women who did not receive the clot-busting drug were 12 percent less likely than men to have a good outcome six months later, or 58 percent of the women compared to 70 percent of men. However, women who were treated with these medications fared about the same as men who took the clot-buster drug.

“There could be many reasons why women who weren’t treated with the clot-busting drug fared worse than men, including biological reasons,” said Hill. “One social reason may be that more than 30 percent of women were widowed compared to seven percent of men at the time of stroke, and therefore did not have a spouse who could act as a caregiver. Also, post-stroke depression is more common in women than in men, which slows down recovery.”

According to a new study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM), obese teenage girls with a greater ratio of visceral fat (fat around internal organs) to subcutaneous fat (fat found just beneath the skin) are likely to have lower bone density than peers with a lower ratio of visceral to subcutaneous fat.

“Visceral fat is known to increase the risk of diabetes and heart disease in obese people,” said Madhusmita Misra, MD, of Massachusetts General Hospital and senior author of the study. “Our study suggests that visceral fat may also have an impact on bone health. This finding is particularly relevant given the rising prevalence of obesity and recent studies suggesting a higher risk of fractures in some obese individuals.”

In this study, researchers examined 30 adolescent girls (15 obese/15 normal weight) between the ages of 12 and 18 years. After measuring weight and height, researchers used magnetic resonance imaging (MRI) to measure subcutaneous and visceral fat tissue and dual energy x-ray absorptiometry (DXA) to assess bone density at the spine, hip and whole body. They found that subcutaneous fat and visceral fat had reciprocal associations with bone density measures, with subcutaneous fat demonstrating positive associations and visceral fat demonstrating inverse associations.

“We do not yet fully understand the chemical mediators of the associations between regional fat and bone health,” said Misra. “It is possible that inflammatory cytokines, types of signaling molecules used in cellular communication, or hormones like adiponectin or leptin are potential mediators of these associations between fat and bone, but further studies are needed to determine their true impact on bone metabolism.”