Tuesday, July 14, 2009
‘even more pathogenic’
Terry Devitt for the University of Wisconsin-Madison News (July 13, 2009)
Study suggests H1N1 virus more dangerous than suspected
A new, highly detailed study of the H1N1 flu virus shows that the pathogen is more virulent than previously thought.
Writing in a fast-tracked report published July 13, 2009 in the journal Nature, an international team of researchers led by UW-Madison virologist Yoshihiro Kawaoka provides a detailed portrait of the pandemic virus and its pathogenic qualities.
In contrast with run-of-the-mill seasonal flu viruses, the H1N1virus exhibits an ability to infect cells deep in the lungs, where it can cause pneumonia and, in severe cases, death. Seasonal viruses typically infect only cells in the upper respiratory system.
"There is a misunderstanding about this virus," says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine and a leading authority on influenza. "People think this pathogen may be similar to seasonal influenza. This study shows that is not the case. There is clear evidence the virus is different than seasonal influenza."
The ability to infect the lungs, notes Kawaoka, is a quality frighteningly similar to those of other pandemic viruses, notably the 1918 virus, which killed tens of millions of people at the tail end of World War I. There are likely other similarities to the 1918 virus, says Kawaoka, as the study also showed that people born before 1918 harbor antibodies that protect against the new H1N1 virus.
And it is possible, he adds, that the virus could become even more pathogenic as the current pandemic runs its course and the virus evolves to acquire new features. It is now flu season in the world's southern hemisphere, and the virus is expected to return in force to the northern hemisphere during the fall and winter flu season.
To assess the pathogenic nature of the H1N1 virus, Kawaoka and his colleagues infected different groups of mice, ferrets and non-human primates — all widely accepted models for studies of influenza — with the pandemic virus and a seasonal flu virus. They found that the H1N1 virus replicates much more efficiently in the respiratory system than seasonal flu and causes severe lesions in the lungs similar to those caused by other more virulent types of pandemic flu.
"When we conducted the experiments in ferrets and monkeys, the seasonal virus did not replicate in the lungs," Kawaoka explains. "The H1N1 virus replicates significantly better in the lungs."
The new study was conducted with samples of the virus obtained from patients in California, Wisconsin, the Netherlands and Japan.
The new Nature report also assessed the immune response of different groups to the new virus. The most intriguing finding, according to Kawaoka, is that those people exposed to the 1918 virus, all of whom are now in advanced old age, have antibodies that neutralize the H1N1 virus. "The people who have high antibody titers are the people born before 1918," he notes.
Kawaoka says that while finding the H1N1 virus to be a more serious pathogen than previously reported is worrisome, the new study also indicates that existing and experimental antiviral drugs can form an effective first line of defense against the virus and slow its spread.
There are currently three approved antiviral compounds, according to Kawaoka, whose team tested the efficacy of two of those compounds and the two experimental antiviral drugs in mice. "The existing and experimental drugs work well in animal models, suggesting they will work in humans," Kawaoka says.
Antiviral drugs are viewed as a first line of defense, as the development and production of mass quantities of vaccines take months at best.
reference:
In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses.
Yasushi Itoh et al
Nature, published on line July 13, 2009 doi:10.1038/nature08260
Link to Nature abstract
Gin and tonic with turkey sandwiches?
Science Daily (July 14, 2009)
Anti-Malarial Drug: Tryptophan Deficiency May Underlie Quinine Side Effects
Researchers have found that the anti-malarial drug quinine can block a cell's ability to take up the essential amino acid tryptophan, a discovery that may explain many of the adverse side-effects associated with quinine. Once confirmed, these findings would suggest that dietary tryptophan supplements could be a simple and inexpensive way to improve the performance of this important drug.
Quinine is a very commonly used anti-malarial drug, yet to this day the principal mode of quinine action against the malaria parasite is still largely unclear, as is the basis for adverse reactions like nausea, headaches, and blurred vision. To address these gaps, Simon Avery and colleagues at the UK’s University of Nottingham took advantage of yeast genetics, examining the effects of quinine on a collection of 6000 yeast mutants, each one lacking exactly one of the yeast's 6000 genes. While quite different from humans, yeast is comparable on a cellular level and yeast is frequently, and successfully, used as front-line agents in testing chemicals and small molecule drugs.
Their screen revealed that strains unable to make tryptophan were extremely susceptible to quinine poisoning, which led them to identify a tryptophan transporter as a key quinine target (yeast that cannot make their own tryptophan have to rely exclusively on external sources, and thus die if tryptophan transport is blocked).
This discovery fits in well with evidence that quinine reactions are more severe in malnourished individuals. Unlike yeast, humans cannot make their own tryptophan and thus require dietary tryptophan, which is abundant in meat but limited in yams, a staple food crop in the tropics where malaria is prevalent. If quinine severely reduces tryptophan uptake, then it follows that people with preexisting tryptophan deficiencies would be especially at risk to this drug.
The authors also note that tryptophan is important as a precursor for the brain chemical serotonin, so the enhanced tryptophan deficiency induced by quinine could explain why many of quinine's side effects are localized to the head region. They also note that side-effects could be averted simply by taking dietary tryptophan supplements in conjunction with quinine treatments, though it is not yet known if tryptophan may affect quinine action against the malaria parasite.
reference:
The Antimalarial Drug Quinine Disrupts Tat2p-mediated Tryptophan Transport and Causes Tryptophan Starvation.
Combiz Khozoie,
Journal of Biological Chemistry, 2009; 284 (27): 17968 DOI: 10.1074/jbc.M109.005843
Link to JBC abstract
regeneration
The University of York (July 13, 2009)
Medical Use For Waste Television Screens
Waste material from discarded televisions could be recycled and used in medicine, according to new research by scientists at the UK’s University of York.
The chemical compound polyvinyl-alcohol (PVA) is widely used in industry and is a key element of television sets with liquid crystal display (LCD) technology. When these sets are thrown away, the LCD panels are usually incinerated or buried in landfill sites.
Researchers have now found a way of recovering PVA from television screens and transforming it into a substance suitable for use in tissue scaffolds which help parts of the body regenerate. They can also be used in pills and dressings that are designed to deliver drugs to particular parts of the body.
Professor James Clark, director of the York Green Chemistry Centre of Excellence and one of the author's of the research, said: "With 2.5 billion liquid crystal displays already reaching the end of their life, and LCD televisions proving hugely popular with consumers, that is a huge amount of potential waste to manage.”
The researchers have developed a technique where recovered material is heated in water in a microwave and washed in ethanol to produced "expanded PVA".
One of this material's key properties is that it does not provoke a response from the human immune system, making it suitable for use in biomedicine.
reference:
Expanding the potential for waste polyvinyl-alcohol.
Andrew J. Hunt et al
Green Chemistry, 2009; DOI: 10.1039/b906607a
Link to Green Chem abstract
‘annoyingly difficult to ignore’
Science Daily (July 13, 2009)
House Cats Know What They Want And How To Get It From You
— Anyone who has ever had cats knows how difficult it can be to get them to do anything they don't already want to do. But it seems that the house cats themselves have had distinctly less trouble getting humans to do their bidding, according to a report published in the July 14th issue of Current Biology.
The rather crafty felines motivate people to fill their food dishes by sending something of a mixed signal: an urgent cry or meowing sound embedded within an otherwise pleasant purr. The result is a call that humans generally find annoyingly difficult to ignore.
"The embedding of a cry within a call that we normally associate with contentment is quite a subtle means of eliciting a response," said Karen McComb of the University of Sussex. "Solicitation purring is probably more acceptable to humans than overt meowing, which is likely to get cats ejected from the bedroom." She suggests that this form of cat communication sends a subliminal sort of message, tapping into an inherent sensitivity that humans and other mammals have to cues relevant in the context of nurturing their offspring.
McComb said that she was inspired by her own cat, who consistently wakes her up in the mornings with a very insistent purr. She learned in talking with other cat owners that some of their cats too had mastered the same manipulative trick. As a scientist who already studied vocal communication in mammals, from elephants to lions, she decided to get to the bottom of it.
It turned out that wasn't so easy to do. The cats were perfectly willing to use their coercive cries in private, but when strangers came around they tended to clam right up. Her team therefore had to train cat owners to record their own cats' cries.
In a series of playback experiments with those calls, they found that humans judged the purrs recorded while cats were actively seeking food as more urgent and less pleasant than those made in other contexts, even if they had never had a cat themselves.
"We found that the crucial factor determining the urgency and pleasantness ratings that purrs received was an unusual high-frequency element—reminiscent of a cry or meow—embedded within the naturally low-pitched purr," McComb said. "Human participants in our experiments judged purrs with high levels of this element to be particularly urgent and unpleasant." When the team re-synthesized the recorded purrs to remove the embedded cry, leaving all else unchanged, the urgency ratings for those calls decreased significantly.
McComb said she thinks this cry occurs at a low level in cats' normal purring, "but we think that cats learn to dramatically exaggerate it when it proves effective in generating a response from humans." In fact, not all cats use this form of purring at all, she said, noting that it seems to most often develop in cats that have a one-on-one relationship with their owners rather than those living in large households, where their purrs might get overlooked by poorly trained people. In those instances, she said, cats seem to find it more effective to stick to the standard meow.
reference
The cry embedded within the purr
Karen McComb,
Current Biology, Volume 19, Issue 13, R507-R508, 14 July 2009 doi:10.1016/j.cub.2009.05.033
Link to Current Biology abstract
gender differences in HIV-1
Science Daily (July 14, 2009)
Why HIV Progresses Faster In Women Than In Men With Same Viral Load
One of the continuing mysteries of the HIV/AIDS epidemic is why women usually develop lower viral levels than men following acute HIV-1 infection but progress faster to AIDS than men with similar viral loads. Now a research team based at the Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard has found that a receptor molecule involved in the first-line recognition of HIV-1 responds to the virus differently in women, leading to subsequent differences in chronic T cell activation, a known predictor of disease progression.
Their paper, which will be published in an upcoming issue of Nature Medicine, is receiving early online release.
"This study may help to account for reported gender differences in HIV-1 disease progression by demonstrating that women and men differ in the way their immune systems respond to the virus," says Marcus Altfeld, MD, PhD, of the Ragon Institute and the MGH Division of Infectious Disease, the study's senior author. "Focusing on immune activation separately from viral replication might give us new therapeutic approaches to limiting HIV-1-induced pathology."
It has become apparent in recent years that HIV-1-infected patients with a high level of immune activation progress to AIDS more rapidly. Why this happens is an area of intense investigation. To explore whether gender-based differences in immune activation were responsible for faster disease progression in women, the Ragon Institute team and their collaborators focused on plasmacytoid dendritic cells (pDCs), among the first cells of the immune system to respond to HIV-1 and other viral pathogens. Earlier studies indicated that pDCs recognize HIV-1 using a receptor called Toll-like receptor 7 (TLR7), leading to production of interferon-alpha and other important immune system molecules.
After initial in vitro experiments showed that a higher percentage of pDCs from uninfected women produced interferon-alpha in response to TLR7 stimulation by HIV-1 than did cells from uninfected men, the researchers examined whether women's hormone levels had any effect on pDC activation. Supporting previous evidence that progesterone may modulate pDC activity, the researchers found that pDCs from postmenopausal women produced levels of interferon-alpha in response to HIV-1 that were closer to levels observed in men. They also found that, in premenopausal women, higher progesterone levels correlated with increased activation of pDCs in response to HIV-1.
Since it is known that the activation of T cells predicts the progression of HIV-1 infection to AIDS, the research team conducted a series of in vitro experiments showing that the stimulation of pDCs in response to HIV-1 led to the subsequent activation of CD8+ T cells by means of interferon-alpha secretion. They then tested blood samples taken from a group of chronically HIV-1-infected women and men prior to treatment initiation and confirmed that women had higher levels of CD8+ T cell activation than did men with the same blood levels of HIV-1.
"Taken together, these results support a model in which the same amount of virus induces stronger pDC activation in women than in men. While stronger activation of the immune system might be beneficial in the early stages of infection, resulting in lower levels of HIV-1 replication, persistent viral replication and stronger chronic immune activation can lead to the faster progression to AIDS that has been seen in women," Altfeld explains.
He adds that the study's results raise a number of important new questions, including exactly how sex hormones modulate the TLR7-mediated response of pDCs to HIV-1 and whether anti-TLR agents may help reduce immune activation in chronic HIV-1 infection. His team is beginning preliminary laboratory studies of the ability of TLR antagonists to reduce HIV-1-induced activation of pDCs.
reference
Sex differences in the Toll-like receptor–mediated response of plasmacytoid dendritic cells to HIV-1
Angela Meier et al
Nature Medicine Published online: 13 July 2009 | doi:10.1038/nm.2004
Link to Nature Medicine abstract
Condoms recommended for reducing the risk of HSV-2
Science Daily (July 13, 2009)
Condoms Associated With Moderate 
Protection Against Herpes Simplex Virus 2
Condom use is associated with a reduced risk of contracting herpes simplex virus 2, according to a report based on pooled analysis of data from previous studies.
Herpes simplex virus 2 (HSV-2) typically causes genital herpes, a chronic, life-long, viral infection. Although studies indicate that consistent condom use reduces the spread of HIV and other sexually transmitted diseases such as chlamydia and gonorrhea, the effectiveness of preventing the transmission of HSV-2 through condom use is less certain, according to background information in the article.
Emily T. Martin, M.P.H., Ph.D., of Children's Hospital Research Institute and the University of Washington, Seattle, and colleagues analyzed data from six HSV-2 studies to assess the effectiveness of condom use in preventing the virus. The studies included three candidate HSV-2 vaccine studies, an HSV-2 drug study, an observational sexually transmitted infection (STI) incidence study and a behavioral STI intervention study. These yielded results from 5,384 HSV-2-negative individuals (average age 29) at baseline for a combined total of 2,040,894 follow-up days.
More than 66 percent of those who took part in the six studies were male, 60.4 percent were white, 94.1 percent were heterosexual and most reported no prior STIs.
A total of 415 of the individuals acquired HSV-2 during follow-up. "Consistent condom users [used 100 percent of the time] had a 30 percent lower risk of HSV-2 acquisition compared with those who never used condoms," the authors write. "Risk of HSV-2 acquisition decreased by 7 percent for every additional 25 percent of the time that condoms were used during anal or vaginal sex." The risk of acquiring the virus increased significantly with increasing frequency of unprotected sex acts. There were no significant differences found in condom effectiveness between men and women.
"Based on findings of this large analysis using all available prospective data, condom use should continue to be recommended to both men and women for reducing the risk of HSV-2 acquisition," the authors conclude. "Although the magnitude of the protective effect was not as large as has been observed with other STIs, a 30 percent reduction in HSV-2 incidence can have a substantial benefit for individuals as well as a public health impact at the population level."
reference:
A Pooled Analysis of the Effect of Condoms in Preventing HSV-2 Acquisition.
Emily T. Martin, MPH et al
Archives of Internal Medicine, 2009;169(13):1233-1240
Link to Arch Int Med abstract
Monday, July 13, 2009
‘needless treatment switches’
Keith Alcorn for Aidsmap (July 13, 2009)
Further evidence of needless treatment switches in absence of viral load testing
Further evidence has emerged that a substantial proportion of switches to second-line treatment in a resource-limited setting, triggered in the absence of viral load testing, are unnecessary and result in an avoidable inflation in drug costs as people switch to more expensive regimens.
The findings, published in the August 1st edition of Clinical Infectious Diseases, are likely to lend further support to calls for viral load testing to be made more accessible in resource-limited settings to confirm cases of suspected treatment failure.
In well-resourced settings everyone receiving treatment undergoes regular viral load testing in order to detect viral rebound and the failure of treatment. Switches to new treatment take place if viral rebound is detected, since the existing regimen becomes ineffective due to drug resistance once viral rebound occurs.
In resource-limited settings viral load testing is rarely available due to cost and lack of well-equipped laboratories.
Reference
Misclassification of first-line antiretroviral treatment failure based on immunological monitoring of HIV infection in resource-limited settings.
Rami Kantor et al
Clinical Infectious Diseases 49: 454-462, 2009. DOI: 10.1086/600396
Link to CID abstract
Editorial Commentary: Monitoring antiretroviral therapy in resource-limited settings: time to avoid costly outcomes
Frederick K. Sawe and James A. McIntyre
Clinical Infectious Diseases 49: 463-464, 2009 DOI: 10.1086/600397.
Link to CID editorial citation
autoimmune and inflammatory diseases
Science Daily (July 12, 2009)
Novel Genetic Finding Offers New Avenue For Future Crohn's Disease Treatment
Researchers from Case Western Reserve University School of Medicine identified a novel link between ITCH, a gene known to regulate inflammation in the body and NOD2, a gene which causes the majority of genetic Crohn's Disease diagnoses. ITCH, when malfunctioning, causes widespread inflammatory diseases, including inflammatory bowel disease, gastritis, uncontrolled skin inflammation, and pulmonary pneumonitis.
Derek Abbott, M.D., Ph.D., and his team of researchers found that ITCH also influences NOD2 -induced inflammation. These findings, published in the August 11th issue of Current Biology, suggest a common pathophysiology exists between multiple inflammatory diseases. The unexpected finding of the interaction between these genes offers the possibility of a new drug target, which would be effective in treating Crohn’s disease – a chronic disorder causing inflammation of the gastrointestinal tract.
Autoimmune and inflammatory diseases are striking an increasing portion of the population. They result from an overstimulation of the immune system by the infectious and environmental agents individuals face daily. Unfortunately, despite their increasing prevalence in the Western world and morbidity among younger patients, the pathophysiology of these enigmatic diseases is poorly understood and for this reason, treatment for these diseases is less-than-ideal.
This finding links two key signaling pathways to the pathophysiology of diseases associated with ITCH and NOD2 and opens new avenues of pharmacologic pursuit to target these diseases. With an eye towards clinical applications, Dr. Abbott and his colleagues' next step is to determine if currently used pharmacologic agents can be useful in this model of inflammatory disease. They will do so using small molecule drug screening to identify potential drugs that target ITCH.
Of those diagnosed with Crohn's disease, 30 percent have the NOD2 mutation in their genes. For these individuals, this discovery opens up the possibility of individually-tailored treatments with better efficacy toward a particular patient's disease.
"This research is an excellent example of how scientific investments benefit the public with measureable gains. In this case, it led to unexpected insights and opened new fields of endeavor for pharmacological manipulation in this serious chronic disease," says Derek Abbott, M.D., Ph.D., assistant professor of pathology, Case Western Reserve University School of Medicine. "This sort of study will help uncover the pathologic mechanism of disease and ultimately lead to more rational and carefully measured treatment."
reference
ITCH K63-Ubiquitinates the NOD2 Binding Protein, RIP2, to Influence Inflammatory Signaling Pathways
MingFang Tao et al
Current Biology, 09 July 2009 doi:10.1016/j.cub.2009.06.038
Link to Current Biology abstract
Coffee and now alcohol?
Science Daily (July 13, 2009)
Regular Moderate Alcohol Intake Has Cognitive Benefits In Older Adults
A glass of wine here, a nightcap there – new research out of Wake Forest University School of Medicine suggests that moderate alcohol intake offers long-term cognitive protection and reduces the risk of dementia in older adults.
The study is being presented at the Alzheimer's Association 2009 International Conference on Alzheimer's Disease (ICAD), in Vienna on July 13.
While previous studies have shown that moderate alcohol intake, particularly wine, is linked with lower risk of heart attacks and dementia, most of the studies have been done in middle-aged people, and it has remained unclear if the benefits of alcohol also apply to older adults in general or to older adults who might already have some mild memory problems. This is the largest, longest U.S. study to look at the effects of regular alcohol intake on dementia in seniors, both with and without memory problems.
"As of yet, we still have no cure for Alzheimer's disease and other dementias, so it is important to look for things that might help people prevent the disease," said Kaycee Sink, M.D., M.A.S, a geriatrician and senior author of the paper. Moderate alcohol intake has been linked to lower risk of heart attacks, stroke, dementia, and death in middle-aged adults, but there is still controversy about alcohol intake in older adults."
For the study, researchers began by examining and interviewing 3,069 individuals, 75 years or older and most without any memory or thinking problems, about their drinking habits. Researchers found that individuals who had no cognitive impairment at the start of the study and drank eight to 14 alcoholic beverages per week, or one to two per day, experienced an average 37 percent reduction in risk of developing dementia compared to individuals who did not drink at all and were classified as abstainers. The type of alcohol consumed did not matter.
For older adults who started the study with mild cognitive impairment, however, consumption of alcohol, at any amount, was associated with faster rates of cognitive decline. In addition, those who were classified in the heavy drinker category, consuming more than 14 drinks per week, were almost twice as likely to develop dementia during the study compared to non-drinkers with mild cognitive impairment.
The results are consistent with previous studies of middle-aged adults that suggest mild to moderate alcohol intake may reduce the risk of dementia, except in the case of individuals who already have mild to moderate cognitive impairment. The researchers' findings support current recommendations not to exceed one drink per day for women and two for men.
"Our results suggest that older adults who are normal cognitively and drink moderately do not need to change their drinking behavior," Sink said. "If you have mild cognitive impairment however, it might benefit you to restrict your drinking and certainly not exceed one drink a day for women and two drinks a day for men.
reference:
Moderate alcohol intake is associated with lower dementia incidence: results from the Ginkgo Evaluation of Memory Study (GEMS).
Kaycee M. Sink et al.
Alzheimer s and Dementia, 2009; 5 (4): P105 DOI: 10.1016/j.jalz.2009.05.329
Link to A & D abstract
Soundbites – New Scientist issue 2716
"If I was in a family that had the familial form of Alzheimer's - where half of individuals have it by age 60 - I would definitely be taking in 500 milligrams of caffeine a day and I would be doing it in coffee."
Gary Arendash at the University of South Florida, on his study suggesting that coffee might reverse Alzheimer's memory problems (ABC news, 6 July)
Risky Sexual Behavior
Science Daily (July 10, 2009)
Risky Sexual Behavior Among Male 
Clients Of Tijuana Sex Workers Heightens Risk Of HIV Transmission
A study by a bi-national team of global health researchers at the University of California, San Diego School of Medicine, examining HIV infection among male clients of female sex workers in Tijuana, has found that over half of male clients had recently had unprotected sex. They also reported a high prevalence of drug use.
"Targeted intervention among male clients is necessary to prevent the spread of HIV and other sexually transmitted infections – intervention that doesn't solely place the onus on female sex workers," said lead author Thomas L. Patterson, of UC San Diego's Department of Psychiatry and the Veterans Administration Health Care System, San Diego.
Tijuana, located in Baja California, directly across the border with San Diego, has a thriving sex industry and is a popular destination for U.S. and foreign sex tourists. While the city's health service does license female sex workers, on condition that they are regularly tested for HIV and other sexually transmitted diseases (STIs), only about half of them are indeed licensed. In addition, Baja California has the second highest cumulative AIDS incidence of any Mexican state and, in 2006, the HIV prevalence among female sex workers in Tijuana was six percent. It has been estimated that as many as one in 112 persons aged 15-49 living in Tijuana is HIV-infected.
"Male clients of female sex workers in the San Diego-Tijuana border region act as a bridge that can potentially transmit HIV and other STIs to sex partners, including their wives," said co-author Manual Gallardo, M.D, Patronato Pro-COMUSIDA in Tijuana. "However, given that only 59% of clients reported regularly using condoms with a female sex worker, there appears to be some level of complacency that urgently needs to be addressed."
Earlier reports by UCSD researchers suggested that interactions with clients can be a critical barrier to the adaptation of safe sex practices among female sex workers, who reported that some clients are willing to pay double for unprotected sex.
"Our new data suggests an urgent need to develop behavioral interventions to improve the clients' knowledge of the risk of HIV," said co-author Steffanie Strathdee, PhD, associate dean for Global Health Sciences at UC San Diego. "Intensified efforts to 'test and treat' should reach out to this high-risk group in ways that are culturally sensitive, recognizing that some men fail to realize that sexual health is a shared responsibility."
reference
Correlates of HIV, sexually transmitted infections, and associated high-risk behaviors among male clients of female sex workers in Tijuana, Mexico
Patterson, Thomas L et al
AIDS, 3 July 2009 doi: 10.1097/QAD.0b013e32832f08a1
Link to AIDS abstract
don't ask, don't tell
Yahoo News covers David Crary’s AP story (July 13, 2009)
Allies' stance cited in US gays-in-military debate
When it comes to dealing with gay personnel in the ranks, the contrasts are stark among some of the world's proudest, toughest militaries — and these differing approaches are invoked by both sides as Americans renew debate over the Pentagon's "don't ask, don't tell" policy.
In the United States, more than 12,000 service members — including dozens of highly trained Arabic linguists — have been dismissed since 1994 because it became known they were gay.
In Britain, on the other hand, gay and lesbian service members marched in crisp uniforms in the annual Pride London parade July 4. Gay Australian soldiers and sailors had their own float in Sydney's Gay Mardi Gras parade. In Israel, the army magazine earlier this year featured two male soldiers on the cover, hugging one another.
U.S. Rep. Patrick Murphy, the first Iraq war veteran elected to Congress, has just launched a campaign for a bill to repeal "don't ask, don't tell." He observed British troops in Iraq operating smoothly with a serve-openly policy and bristles at the contention that America's armed forces would suffer morale and recruiting problems if they followed suit.
"I take it as a personal affront to our warriors," said the Pennsylvania Democrat. "To say that other countries' soldiers are professional enough to handle this and American soldiers aren't is really a slap in the face."
In the article Associated Press reporters took an in-depth look at how the militaries of Israel, Britain and Australia have managed with serve-openly policies, and interviewed partisans on both sides of the debate in the United States about the relevance of those experiences.
Sunday, July 12, 2009
Chris Riddell - The Observer
Dave Brown - The Independent
The TelegraphRichard Pérez-Peña’s article in the New York Times Business Section (July 13, 2009)
is available for those who want more of the story.
regulation = far less gun trafficking
Science Daily (July 7, 2009)
Regulation And Oversight Of Gun Sales Reduces Trafficking To Criminals, Study Finds
Comprehensive regulation of gun sellers appears to reduce the trafficking of guns to criminals, according to a study led by researchers at the Johns Hopkins Bloomberg School of Public Health. Preventing the diversion of guns to criminals is important because 85 percent of guns recovered by police were recovered from criminal suspects who were not the original purchasers of the guns according to prior research from the Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF).
The Hopkins study is the first to gather and incorporate measures of the enforcement of gun sale laws into a study of the effectiveness of those laws. It is available online in the Journal of Urban Health and in the just-released July 2009 print edition.
“In the U.S., few states have a comprehensive system to keep firearms sellers accountable,” said the study’s lead author Daniel Webster, ScD, MPH, and co-director of the Bloomberg School’s Center for Gun Policy and Research and associate professor in the Bloomberg School’s Department of Health Policy and Management. “Our analysis found that the states with strong regulations and oversight of gun dealers, as well as regulation of private sellers, have far less gun trafficking than do states that lack these measures.”
U.S. federal law requires gun dealers to be licensed by the ATF, keep records of sales, and ensure that purchasers have passed a background check. Some states place additional regulations over gun retailers such as mandatory inspections and anti-theft security measures. Federal gun law also permits private sellers to transfer guns without a background check or record keeping. Fifteen states regulate gun sales by all private sellers and two additional states regulate private gun sales at gun shows.
For the study, researchers examined state laws governing gun sales using data from ATF crime gun traces from 54 U.S. cities. The analysis also included a survey of law enforcement agencies’ practices to promote compliance with gun sale laws and data tracing the initial point of sale of guns recovered from crimes. A gun was considered to have been trafficked if it had been purchased within a year of being recovered from a crime scene unless the criminal was also the legal purchaser of record. The variables examined included: strong gun dealer regulation and oversight; state and local law enforcement agency use of undercover stings of gun dealers; regulation of private gun sales; laws requiring a permit or license to purchase a handgun; and limiting the purchase of guns to one gun per customer per month.
According to the study, cities with the lowest levels of in-state gun trafficking were Santa Ana, CA; Camden and Newark, NJ; New York, NY; and Boston, MA. Each of these cities was in a state that regulates private sales of handguns, four had strong gun dealer oversight and four had discretionary handgun purchase licensing systems. Cities with the highest levels of in-state gun trafficking were Gary, IN; Tucson, AZ; Phoenix, AZ; Albuquerque, NM; and Indianapolis, IN. None of these cities had any of the gun sales accountability measures examined in the study.
Overall, in-state gun trafficking was 2 to 4 times higher in cities located in states without these gun sales regulations. The study found no effect on gun trafficking within the state from laws limiting handgun sales to a maximum of one gun per person per month. (The study did not examine the effect of one-gun-per-month laws on interstate trafficking. The findings from prior studies of these laws suggest that they reduce interstate gun trafficking.)
“While some have questioned the ability of gun sales regulations to keep guns from criminals, our findings are consistent with other studies which found that measures intended to enhance gun seller accountability can significantly curtail the flow of new guns to criminals,” said co-author Jon Vernick, JD, MPH, co-director of the Center for Gun Policy and Research and associate professor in the Department of Health Policy and Management.
In 2005, firearms were used in more than 12,000 homicides in the United States, with 84 percent occurring in large- and medium-sized metropolitan areas.
Link to Johns Hopkins Center for Gun Policy and Research
reference
Effects of State-Level Firearm Seller Accountability Policies on Firearm Trafficking
Daniel W. Webster, Jon S. Vernick and Maria T. Bulzacchelli
Journal of Urban Health Volume 86, Number 4 / July, 2009 p 525-537 10.1007/s11524-009-9351-x
Link to JUH abstract
Saturday, July 11, 2009
Spread your sperm the smart way
Science Daily (July 10, 2009)
Attractive Males Release Fewer Sperm
Attractive males release fewer sperm per mating to maximize their chances of producing offspring across a range of females, according to a new paper on the evolution of ejaculation strategies. The findings by researchers at UCL (University College London) and the University of Oxford suggest that, paradoxically, matings with attractive males may be less fertile than those with unattractive ones.
In a paper to be published in the journal American Naturalist, the team mathematically modeled a range of male ejaculation strategies to look for the optimum “sperm load” per mating, and how this might vary depending on mating patterns. Previous studies have shown that in animals such as the domestic fowl, and fish such as the Arctic charr, males with privileged access to females produce ejaculates of lower fertilizing quality than subordinate males.
Sam Tazzyman, UCL CoMPLEX (Centre for Mathematics and Physics in the Life Sciences and Experimental Biology), says: “In some species, females mate with many different males. Each male’s sperm competes with that of other males in a process known as ‘sperm competition’. Since males have finite resources to allocate to breeding, they allocate them carefully to each mating to maximize their number of offspring. If a male puts a lot of resources into each mating he will get more offspring per mating, but at the expense of fewer matings. If, on the other hand, a male puts few resources into each mating he will secure less paternity per mating, but will be able to carry out more matings overall. Thus, there is a trade-off between number of matings and success per mating."
“How a male negotiates this trade-off depends on how easy he finds it to attract females. The more attractive a male is, the more females will be willing to mate with him, reducing the value of each mating to him. This means it is optimal for him to contribute fewer sperm per mating. Although this reduces fertility per mating, it maximizes the number of offspring he sires overall. Less attractive males secure fewer matings but value each of them more highly, and by allocating more sperm to each mating make the most of their meager opportunities. This leads to the rather paradoxical prediction that matings with attractive males may be less fertile than those with unattractive males."
“There are as yet few good examples of this process found in nature, as it has generally been assumed that more attractive or higher quality males will be more fertile. A possible case can be seen in chickens, which in the wild live in groups of varying numbers of males and females. Females mate with many males, so males are subject to sperm competition. However, the attractiveness of a male is determined in large part by his social standing. Males higher up the pecking order find it easier to secure matings with the females, but they transfer fewer sperm to females. In addition, the sperm of dominant birds is less motile and has lower fertilizing efficiency than the sperm of subordinate birds. Scientists can artificially change the pecking order, and when this is done, the new dominant male's sperm quickly loses motility, while that of males reduced to subordinate status increases in motility.”
“Further work in this area should look at males that are similarly attractive, but have different levels of resources to allocate to sperm production, to see how this alters their sperm number and quality. The model should also be expanded to include the effects of short-term sperm depletion, which is known to affect ejaculate content when males re-mate quickly. We also would like to explore whether the lower fertility of attractive males causes females to start avoiding attractive males that mate too often, as these males reduce their fertility.”
“Finally, how this work applies to humans and other primates is not yet known. Human attractiveness is complicated and influenced by a number of factors including cultural preferences. Nonetheless, ejaculate size and sperm quality are likely to have been molded by similar forces, like attractiveness and the number of sexual partners, that are important in other species.”
reference:
The evolution of continuous variation in ejaculate expenditure strategy
Samuel J. Tazzyman, Tommaso Pizzari, Robert M. Seymour and Andrew Pomiankowski
American Naturalist, (174 September, 2009) DOI: 10.1086/603612
Link to American Naturalist [September issue not yet available]
Student drinking – changing perceptions
Science Daily (July 8, 2009)
Student Drinking: Changing Perceptions Reduces Alcohol Misuse
Giving students personalized feedback on their drinking behavior and how it compares to social norms might help to reduce alcohol misuse, according to a study published in Cochrane Systematic Review.
A large body of social science research has established that students tend to overestimate the amount of alcohol that their peers consume. This overestimation causes many to have misguided views about whether their own behavior is normal and may contribute to the 1.8 million alcohol related deaths every year. Social norms interventions that provide feedback about own and peer drinking behaviors may help to address these misconceptions.
Researchers analyzed data from 22 trials that together included 7,275 college and university students, mostly studying in the US. They found that students who were provided with personalized feedback via the internet or individual face-to-face sessions drank less often and indulged in less binge drinking than those in control groups. Web-based feedback also resulted in significant reductions in blood alcohol content and alcohol related problems.
Group counseling and mailed feedback were not found to be effective compared to control interventions, although the researchers say further studies comparing the different ways of providing social normative feedback are required. "We can't make direct comparisons between the different interventions, but based on a small number of studies web-based interventions would certainly seem to be a cost-effective option for reducing alcohol misuse," said lead researcher Maria Teresa Moreira, from the School of Health and Social Care at Oxford Brookes University in the UK.
"We know that social norms have a powerful impact on thought and behavior, so changing people's perceptions about what is normal can really help. Most of the effects lasted for a few months, but some lasted over a year, particularly for the web-based feedback," added Moreira.
reference
Social norms interventions to reduce alcohol misuse in University or College students.
Maria Teresa Moreira, Lesley A Smith, David Foxcroft
Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD006748. DOI: 10.1002/14651858.CD006748.pub2.
Link to the Cochrane Library abstract
biological response to psychotherapy
Science Daily (July 6, 2009)
Psychotherapy Of Depression Changes Biological Parameters?
A group of German investigators demonstrated that the early increase in phosphorylated CREB (pCREB) is related to treatment response and does not depend on pharmacological interventions or brain-derived neurotrophic factor (BDNF) plasma levels. For the first time, cellular biological markers could be associated with response to psychotherapy.
The cyclic adenosine monophosphate response element-binding proteins (CREB) and their interaction with brain-derived neurotrophic factor (BDNF) are essential elements in signal transduction pathways important for cellular resilience and neuroplasticity. They play a decisive role in the concept of altered neuroplasticity in major depression.
The Authors of this study have previously demonstrated that the increase in phosphorylated CREB (pCREB) in T lymphocytes is significantly associated with clinical improvement in patients treated with antidepressants. In the present study, they focused on patients treated only with psychotherapy to exclude direct pharmacological actions.
In addition to pCREB, they also measured the BDNF plasma levels. pCREB in T lymphocytes was determined by Western blot; the BDNF plasma levels with solid-phase ELISA. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD).
Thirty patients meeting DSM-IV criteria for major depressive episodes (MDE) were recruited into this 6-week study. They received interpersonal psychotherapy (IPT) twice weekly. After 6 weeks of IPT, 17 patients responded (reduction of 50% of baseline HAMD); after 1 week of treatment pCREB increased significantly compared to the nonresponder group. Measurement of the BDNF plasma levels revealed no differences between the responder and nonresponder groups.
Furthermore, the correlations between BDNF plasma levels and pCREB were not significant. The early increase in pCREB is related to treatment response and does not depend on pharmacological interventions or BDNF plasma levels. For the first time, cellular biological markers could be associated with response to psychotherapy.
reference:
Changes in CREB Phosphorylation and BDNF Plasma Levels during Psychotherapy of Depression.
Jakob M. Koch et al
Psychotherapy and Psychosomatics, 2009; 78 (3): 187 DOI: 10.1159/000209350
Link to Psychotherapy and Psychosomatics abstract
Friday, July 10, 2009
ebola
BBC News on line (July 10, 2009)
Discovery of Swine as a Host for the Reston ebolavirus
Roger W. Barrette et al,
Science 10 July 2009: Vol. 325. no. 5937, pp. 204 – 206 DOI: 10.1126/science.1172705
Link to Science abstract
Concern over Ebola virus in pigs
A form of Ebola virus has been detected in pigs for the first time, raising concerns it could mutate and pose a new risk to humans. Ebola-Reston virus (REBOV) has only previously been seen in monkeys and humans - and has not caused illness. But researchers are concerned that pigs might provide a melting pot where the virus could mutate into something more menacing for humans.
However, the researchers, from the US Centers for Disease Control and Prevention, stress that the virus at present appears to pose no risk to humans.
It has been detected in farm workers who tend the infected pigs, and they have shown no signs of illness. However, writing in Science, the researchers said: "REBOV infection in domestic swine raises concern about the potential for emerging disease in humans and a wider range of livestock.
"There is concern that its passage through swine may allow REBOV to diverge and shift its potential for pathogenicity."
REBOV belongs to the family of filoviruses which usually target primates.
These viruses cause viral haemorrhagic fevers, which cause extensive internal bleeding, and can be fatal.
The latest study examined tissue samples taken from pigs from different parts of the Philippines suffering from unusually severe respiratory infections.
Analysis showed that the animals were infected with widely varying strains of the virus, suggesting it may have circulated widely in pigs even before it was first discovered in monkeys exported to the US from the Philippines in 1989.
The researchers said it was possible that REBOV originally emerged in another, as yet unidentified, host. Fruit-eating bats have been suggested as one possibility.
Pigs are known to provide an ideal host for viruses to mutate. Experts say the potential risk is magnified because they are an essential part of the human food chain, and come into close contact with people.
Researcher Dr Michael McIntosh said: "We know this family of viruses are associated with fatal illnesses in humans.
"Even though there is no evidence at this time to suggest REBOV causes diseases in humans it does seem that it can infect humans, and be transmitted from swine to humans.”
"The effect of such an infection on an immuno-compromised host - humans or swine - is also an unknown factor of concern."
The World Health Organization says that pork is still safe to eat, provided it is prepared and cooked properly.
ReferenceDiscovery of Swine as a Host for the Reston ebolavirus
Roger W. Barrette et al,
Science 10 July 2009: Vol. 325. no. 5937, pp. 204 – 206 DOI: 10.1126/science.1172705
Link to Science abstract
HIV-related stigma
Michael Carter for Aidsmap (July 10, 2009)
Poor health and lack of support associated with HIV-related stigma
High levels of stigma are experienced by people with HIV, and this is consistently associated with lack of social support, poor physical and mental health, poverty, and younger age, according to the results of a meta-analysis published in the June edition of AIDS Care. A total of 24 studies conducted since 2000, involving a wide range of people with HIV, were included in the analysis.
The authors suggest “health professionals caring for people living with HIV as well as HIV-related stigma interventions and support programs could benefit from an enhanced understanding of correlates of HIV-related stigma.”
Stigma has been associated with HIV since the beginnings of the epidemic and is experienced by individuals in different ways.
HIV-positive people are often blamed for their infection, on occasion even by healthcare providers. HIV also disproportionately affects groups that are already stigmatized, including gay men, injecting drugs users and migrant populations.
Earlier research has shown that HIV-related stigma is associated with mental health needs, social exclusion, lower quality of life, and poor physical health. Moreover, studies have also indicated that age, gender, income, race/ethnicity, and sexual orientation are associated with stigma.
However, studies examining HIV-related stigma have varied by their sample size and population, measures of stigma, data collection and statistical analysis. It has therefore been difficult to compare their findings, or generalize them to wider populations of individuals living with HIV.
Investigators therefore conducted a meta-analysis of recently published studies that measured HIV-related stigma. Their aims were to establish the strength and direction of the association between HIV-related stigma and physical, mental and emotional health, and also to determine the associations between stigma and a number of demographic characteristics.
A total of 24 studies published in peer-reviewed journals since 2000 were included in this analysis. These studies involved a total of 5600 HIV-positive individuals from diverse backgrounds.
The investigators found that “high stigma levels were consistently and significantly associated with lack of social support, poor physical health, poor mental health, lower income and younger age.”
The authors recommend that “effective interventions to challenge HIV-related stigma should operate on multiple levels and target several populations.” Wider-ranging structural interventions are also needed, and the authors suggest these should provide “legal protection from HIV-related stigma and discrimination as well as address poverty through increasing access to employment for people living with HIV and ensuring adequate disability insurance”.
Reference
Meta-analysis of health and demographic correlates of stigma towards people living with HIV.
C. Logie and T. M. Gadalla
AIDS Care 21: 742-53, 2009.
Link to AIDS Care abstract
Less = longer
Michael Torrice for ScienceNOW Daily News (9 July 2009)
Calorie-Counting Monkeys Live Longer
Rodents, yeast, and roundworms all have something in common: They live longer when they consume less. Now a primate has joined the calorie-restriction club. After 20 long years of waiting, scientists have concluded that rhesus monkeys that eat nearly a third less food than normal monkeys age more slowly. The results come as close as any can to proving that calorie restriction could significantly slow aging in humans--even if such a lean diet would not appeal to most of us.
Researchers first discovered the connection between lean diets and extended life spans in a 1935 study of calorie-restricted rats. In the past decade, studies in yeast and worms have pinpointed some genes that may be responsible. Scientists believe the genes somehow ramp up systems to protect an organism from environmental stress and may have evolved to help organisms survive in environments where food was scarce. In rodent studies, calorie restriction can extend life span by 20% to 80%. Whether calorie restriction also slows aging in primates wasn't known, however.
Two decades ago, three different research groups in the United States decided to fill this gap. The groups have previously published updates on their monkeys' health, but in Science, one of them reports survival data from their colony of 76 rhesus monkeys. The team, led by gerontologist Richard Weindruch of the University of Wisconsin, Madison, began monitoring the animals when they hit 7 to 14 years old--monkey adulthood. Researchers allowed half of the monkeys to eat as much as they wanted during the day, while restricting the other half to a diet with 30% fewer calories. The scientists gave the restricted monkeys vitamin and mineral supplements to ensure they did not suffer malnutrition and treated any animals that fell sick, says Weindruch.
Studying aging in monkeys takes patience. Mice and rats only live for a couple of years, while these monkeys can live to 40, and the average life span is 27 years. Now that the surviving monkeys have reached their mid- to late 20s, the Wisconsin group could glean how calorie restriction was affecting their life span. Sixty-three percent of the calorie-restricted animals are still alive compared to only 45% of their free-feeding counterparts. For age-related deaths caused by illnesses such as cardiovascular disease and cancer, the voracious eaters died at three times the rate of restricted monkeys: 14 versus five monkeys, respectively. Another seven control and nine lean monkeys died from causes not related to aging such as complications from anesthesia or injuries. Leaner diets also reduced muscle and brain gray matter deterioration, two conditions associated with aging. (The team has not yet studied cognitive differences between the two groups.)
Researchers who study aging are split on how much stock to put in the study. Leonard Guarente, a molecular biologist at the Massachusetts Institute of Technology in Cambridge who has studied aging in yeast, believes that not enough monkeys have died yet to make definitive comparisons between the two groups. As of March, when Weindruch's group submitted the paper, about half of the colony was still alive. "The gap [in survival rates] may separate more, but it's still too early to tell," Guarente says. On the other hand, molecular biologist Matthew Kaeberlein of the University of Washington, Seattle, thinks the gap as it stands now is still compelling. He points to the difference in age-related deaths between the two groups as the more relevant statistic. "The fact that they see a significant effect at this point suggests there will be a robust effect when they finish the study," he says.
Weindruch and his collaborators plan to continue monitoring the remaining monkeys, which could stretch the study's length past 3 decades. "If we reach the 40-year-old life span, the study could continue for another 15 years," Weindruch said. "That would probably round out my career."
reference
Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys
Ricki J. Colman, et al
Science 10 July 2009: Vol. 325. no. 5937, pp. 201 – 204 DOI: 10.1126/science.1173635
Link to Science abstract
first-line HIV treatment
Michael Carter for Aidsmap (July 10, 2009)
Raltegravir approved for first-line HIV treatment in US
The integrase inhibitor raltegravir ( sold commercial by Merck & Co as Isentress) has been approved by the the US Food and Drug Administration (FDA) for use by individuals starting HIV treatment for the first time.
On July 9th the FDA announced that it had granted approval for the use of raltegravir in combination with other antiretrovirals by treatment-naïve patients. The use of the drug had previously been restricted to treatment-experienced patients.
Approval for first-line use was based on the results of the 48-week STARTMRK study that showed that raltegravir was non-inferior to efavirenz (Sustiva), when taken with FTC and tenofovir by patients initiating HIV therapy.
Research indicates that raltegravir appears to cause only mild to moderate side-effects, with 4% of individuals who took the drug in the STARMRK study reporting headache and 3% nausea.
Raltegravi is an integrase inhibitor that it works by blocking the enzyme integrase, one of three types of enzymes the AIDS virus uses to reproduce and infect cells.
Raltegravir’s approved dose is 400 mg twice-daily with or without food.
The European license for raltegravir currently restricts its use to treatment-experienced patients but an application for first-line use in Europe is currently under review.
earlier initiation of HIV therapy
Michael Carter for Aidsmap (July 09, 2009)
Immune suppression increases risk of death from non-AIDS-defining illnesses
Over half the deaths observed in a large cohort of HIV individuals in the combination antiretroviral therapy era who were followed from seroconversion were due to non-AIDS-related illnesses, investigators from the CASCADE cohort study report in the online edition of the journal AIDS.
The researchers found that deaths due to liver disease, infections, respiratory diseases and non-AIDS-defining cancers were all related to immune deficiency. Although deaths because of cardiovascular disease were not related to CD4 cell count, they were associated with a high viral load.
HIV treatment guidelines have been changed in many countries to recommend earlier initiation of HIV therapy to reduce the risk of death from non-HIV-related causes. The investigators believe that their findings strong support such guidance and write: “The consistent finding of a raised risk of non-AIDS-defining death and cumulative time spent with a CD4 cell count less than 350 cells/mm3 reveals clinically important information and provides a strong argument that HIV-infected patients may benefit from early initiation of antiretroviral treatment to reduce the risk of AIDS and non-AIDS-related causes of death.”
“Our results add to the growing body of evidence of the association of immunodepletion and important non-AIDS-related morbidity”, conclude the investigators.
Reference
Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy.
Marin, Benoît et al on behalf of the CASCADE Collaboration
AIDS 23 (online edition), 2009. doi: 10.1097/QAD.0b013e32832e9b78
Link to AIDS abstract
Thursday, July 09, 2009
28%-38% longer life
University of Texas Health Science Center, San Antonio (July 8, 2009)
Easter Island Compound Extends Lifespan Of Old Mice
The giant monoliths of Easter Island are worn, but they have endured for centuries. New research suggests that a compound first discovered in the soil of the South Pacific island might help us stand the test of time, too.
In the journal Nature, The University of Texas Health Science Center at San Antonio and two collaborating centers reported that the Easter Island compound – called "rapamycin" after the island's Polynesian name, Rapa Nui – extended the expected lifespan of middle-aged mice by 28 percent to 38 percent. In human terms, this would be greater than the predicted increase in extra years of life if cancer and heart disease were both cured and prevented.
The rapamycin was given to the mice at an age equivalent to 60 years old in humans.
The studies are part of the National Institute on Aging (NIA) Interventions Testing Program, which seeks compounds that might help people remain active and disease-free throughout their lives. The other two centers involved are the University of Michigan at Ann Arbor and Jackson Laboratory in Bar Harbor, Maine.
The Texas study was led by scientists at two institutes at the UT Health Science Center: the Institute of Biotechnology (IBT) and the Barshop Institute for Longevity and Aging Studies.
Discovered in the 1970s, rapamycin was first noted for its anti-fungal properties and later was used to prevent organ rejection in transplant patients. It also is used in stents, which are implanted in patients during angioplasty to keep coronary arteries open. It is in clinical trials for the treatment of cancer.
The new aging experiments found that adding rapamycin to the diet of older mice increased their lifespan. The results were the same in Texas, Michigan and Maine.
Aging researchers currently acknowledge only two life-extending interventions in mammals: calorie restriction and genetic manipulation. Rapamycin appears to partially shut down the same molecular pathway as restricting food intake or reducing growth factors.
It does so through a cellular protein called mTOR (mammalian target of rapamycin), which controls many processes in cell metabolism and responses to stress.
reference
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
David E. Harrison et al
Nature advance online publication 8 July 2009 | doi:10.1038/nature08221
Link to Nature abstract
Alzheimer’s – language predicts?
Science Daily (July 9, 2009)
Language Skills In Your Twenties May Predict Risk Of Dementia Decades Later
People who have superior language skills early in life may be less likely to develop Alzheimer’s disease decades later, despite having the hallmark signs of the disease, according to research published in the July 9, 2009, online issue of Neurology®, the medical journal of the American Academy of Neurology.
"A puzzling feature of Alzheimer’s disease is how it affects people differently," said study author Juan C. Troncoso, MD, with Johns Hopkins University in Baltimore. "One person who has severe plaques and tangles, the telling signs of Alzheimer’s disease in their brains, may show no symptoms affecting their memory. Another person with those same types of plaques and tangles in the same areas of the brain might end up with a full-blown case of Alzheimer’s disease. We looked at how language ability might affect the onset of symptoms."
Researchers examined the brains of 38 Catholic nuns after death. The participants were part of the Nun Study, an ongoing clinical study of Catholic sisters of the School Sisters of Notre Dame congregation living in the United States. Scientists determined two groups: women with memory problems and Alzheimer’s disease hallmarks in the brain and women with normal memory with or without signs of Alzheimer’s disease in the brain.
The researchers analyzed essays that 14 participants wrote as they entered the convent in their late teens or early 20's. They studied the average number of ideas expressed for every 10 words. The analysis also measured how complex the grammar was in each essay.
The study found that language scores were 20 percent higher in the women without memory problems compared to those with memory problems. The grammar score, however, did not show any difference between the two groups.
"Despite the small number of participants in this portion of the study, the finding is a fascinating one," Troncoso said. "Our results show that an intellectual ability test in the early 20s may predict the likelihood of remaining cognitively normal five or six decades later, even in the presence of a large amount of Alzheimer’s disease pathology."
The study also measured how growth in brain cells might be part of the brain cell's early response to Alzheimer’s disease or how these cells may prevent memory impairment despite a large amount of Alzheimer’s disease lesions. The study found significant increases in the size of brain cells in nuns with normal thinking skills and Alzheimer’s disease hallmarks compared to people with memory problems and those with normal thinking skills and without the signs of Alzheimer’s disease.
"Perhaps mental abilities at age 20 are indicative of a brain that will be better able to cope with diseases later in life," said Troncoso.
reference
The Nun Study. Clinically silent AD, neuronal hypertrophy, and linguistic skills in early life
D. Iacono, et al
Neurology, first published on July 8, 2009 as doi: doi:10.1212/WNL.0b013e3181b01077
Link to Neurology abstract
‘Suicides are just the tip of the iceberg’
Science Daily (July 8, 2009)
Financial Crisis Increases Suicides And Homicides, Study Finds
Market crashes could lead to rises in homicides and suicides, unless governments invest in labor market protections, according to a study published in The Lancet.
Researchers at London School of Hygiene & Tropical Medicine and Oxford University estimated that soaring stress brought on by job losses could prompt a 2.4% rise in suicide rates in people under-64 years of age, a 2.7% rise in heart attack deaths in men between 30 and 44 years, and a 2.4% rise in homicides rates, corresponding to thousands of deaths in European Union countries, such as the UK.
Government spending to keep people in employment and quickly get them back to work when they lose jobs could prevent these rises in deaths from occurring, the study says. When spending on such "active labor market programs" is above US $190 (£115; €135) per person, financial crisis would not be a major killer.
The report also suggests that in poor countries, where investments in active labor market programs are much lower or virtually non-existent, the death toll brought on by the financial meltdown would be much worse.
The study was written in the wake of concerns that health might suffer as a result of the financial crisis. It is thought to be the most comprehensive evaluation of the relationship between economic crises, unemployment and mortality in Europe and the first to consider the role of specific government responses.
"Financial crisis causes hardship for many ordinary people, but it does not have to cost them their lives", social epidemiologist David Stuckler, who led the research said. He continued, "Our findings show that investing in active labor market programs can both help the economy and save lives."
The researchers studied mortality rates for over 30 causes of death from the World Health Organization’s Health for All Database between the years 1970 and 2007. They then compared the results to unemployment data from the International Labour Organisation, and data from the Organisation for Economic Co-operation and Development describing different types of government social program expenditures during the same period. Models were used to control variables such as past employment and mortality trends, differing degrees to which countries monitor suicides and unemployment, and population ageing.
Previous studies in individual countries had found mixed results – in Sweden, finding no effect of financial crises on health, but in Spain and the US, finding some negative effects and in some cases improved health. The researchers found that whether more people died depended on how much countries spent on social protections, including active labor market programs.
In the UK, where currently about US$150 (£91; €107) per head per year is spent active labor market programs, the researchers estimated that at least 25 to 290 suicides would occur as a direct result of the financial crisis.
Professor Martin McKee at the London School of Hygiene & Tropical Medicine and one of the report's authors, noted that "Suicides are just the tip of the iceberg – rising suicide rates are a sign of many failed suicide attempts and high levels of mental distress among workers and families."
As with any ecological study, the analysis had several limitations. The analysis focused on the experience of entire populations, and vulnerable groups, such as migrants or refugees, could suffer disproportionately even when social spending was high. Data on social protections were also missing for many countries, in particular for most central and eastern European countries, where unemployment rates tended to be higher than the west EU and social spending was much lower.
The researchers estimated that rising unemployment rates by 3% could prompt a 2.4% rise in suicide rates in people under-64 years of age and a 2.4% rise in homicides rates, but a drop in traffic fatalities by 4.2% in European Union countries, such as the UK. The study's findings were consistent with recent reports in the UK of rising suicides and falling traffic volume. Unemployed persons have two times the risk of death as employed persons due to suicides, and during recession people walk instead of drive or use public transit, reducing risks of road injury and death.
Sanjay Basu, at University of California at San Francisco pointed out that, "The analysis suggests that governments may be able to do something to protect their populations, specifically by budgeting for measures that help people get back into work." He continued, "This report shows that government spending programs designed to stimulate the economy could also be used to prevent potentially thousands of deaths."
reference
The public health effect of economic crises and alternative policy responses in Europe: an empirical analysis
David Stuckler, Sanjay Basu, Marc Suhrcke, Adam Coutts, Martin McKee
The Lancet, Early Online Publication, 8 July 2009 doi:10.1016/S0140-6736(09)61124-7
Link to The Lancet abstract
Andreas Lundin, Tomas Hemmingsson
The Lancet, Early Online Publication, 8 July 2009 doi:10.1016/S0140-6736(09)61202-2
Link to The Lancet abstract
Wednesday, July 08, 2009
Sperm Created
UK’s Newcastle University(July 8, 2009)
Human Sperm Created From Embryonic Stem Cells
Human sperm have been created using embryonic stem cells for the first time in a scientific development which will lead researchers to a better understanding of the causes of infertility.
Researchers led by Professor Karim Nayernia at Newcastle University and the North East England Stem Cell Institute (NESCI)* have developed a new technique which has made the creation of human sperm possible in the laboratory. NESCI is a collaboration between Newcastle and Durham Universities, Newcastle NHS Foundation Trust and other partners
The work is published July 8th 2009 in the academic journal Stem Cells and Development.
Professor Nayernia says: "This is an important development as it will allow researchers to study in detail how sperm forms and lead to a better understanding of infertility in men – why it happens and what is causing it. This understanding could help us develop new ways to help couples suffering infertility so they can have a child which is genetically their own."
"It will also allow scientists to study how cells involved in reproduction are affected by toxins, for example, why young boys with leukemia who undergo chemotherapy can become infertile for life – and possibly lead us to a solution."
The team also believes that studying the process of forming sperm could lead to a better understanding of how genetic diseases are passed on.
In the technique developed at Newcastle, stem cells with XY chromosomes (male) were developed into germline stem cells which were then prompted to complete meiosis - cell division with halving of the chromosome set. These were shown to produce fully mature, sperm called scientifically, In Vitro Derived sperm (IVD sperm).
In contrast, stem cells with XX chromosomes (female) were prompted to form early stage sperm, spermatagonia, but did not progress further. This demonstrates to researchers that the genes on a Y chromosome are essential for meiosis and for sperm maturation.
IVD sperm
The IVD sperm will not and cannot be used for fertility treatment. As well as being prohibited by UK law, the research team say fertilization of human eggs and implantation of embryos would hold no scientific merit for them as they want to study the process as a model for research.
"While we can understand that some people may have concerns, this does not mean that humans can be produced 'in a dish' and we have no intention of doing this. This work is a way of investigating why some people are infertile and the reasons behind it. If we have a better understanding of what's going on it could lead to new ways of treating infertility," adds Professor Nayernia.
Technique
The Newcastle University team have developed a method for establishing early stage sperm from human embryonic stem cells in the laboratory.
The embryonic stem cells were cultured in a new medium containing vitamin A derivative (retinoic acid), in a new technique established by the team. Based on this technique, the cells differentiated into germline stem cells.
These expressed a protein which was stained with a green fluorescent marker and they were separated out by FACSTM (Fluorescence-activated cell sorting) using a laser.
After further differentiation, these in vitro derived germline stem cells expressed markers which are specific to primordial germ cells, spermatogonial stem cells, meiotic (spermatocytes) and post meiotic germ cells (spermatids and sperm).
These results indicated maturation of the primordial germ cells to haploid male gametes – called IVD sperm - characterised by containing half a chromosome set (23 chromosomes).
reference:
In Vitro Derivation of Human Sperm from Embryonic Stem Cells
Karim Nayernia, Jae Ho Lee, Majlinda Lako et al
Stem Cells and Development ahead of print. doi:10.1089/scd.2009.0063.
Link to Stem Cells and Development abstract
man -- woman
Science Daily (July 8, 2009)
Different Clues To The Health Of Women And Men
A study by Carita Håkansson, senior lecturer at the School of Health Sciences, Jönköping in Sweden, shows that meaning and balance in everyday life are predictors of health among women. However, the most important predictor of health among men is their ability to manage the demands of their working life.
Having energy left over for domestic chores and leisure activities after work influences women’s subjective health in a positive way. Furthermore, good subjective health among women is influenced by their experience of meaningfulness both at work, and in activities outside work. However, having time and energy to manage the demands of their working life is the most important factor influencing men’s subjective health.
Whether women have time and energy to manage the combined demands of their career and their domestic chores influences their attendance at work, whereas it is the stress of their career which actually influences men’s attendance. The results are based on a survey of 2,683 women and men in a working population in Sweden, who participated in a postal survey by responding to questions twice, with a two-year interval.
“Women who are not able to meet the demands of their working life and private life perceive themselves as being stressed, which may lead to sick leave, while men’s health is mainly influenced by their working life” Håkansson said.
The study shows that different strategies are needed to promote health and increase employment among women and men.
Fear
Joel Schwarz for University of Washington News (July 6, 2009)
Finding fear: Neuroscientists locate where it is processed in mammalian brain
Fear is a powerful emotion, and neuroscientists have for the first time located the neurons responsible for fear conditioning in the mammalian brain. Fear conditioning is a form of Pavlovian, or associative, learning and is considered to be a model system for understanding human phobias, post-traumatic stress disorder and other anxiety disorders.
Using an imaging technique that enabled them to trace the process of neural activation in the brains of rats, University of Washington researchers have pinpointed the basolateral nucleus in the region of the brain called the amygdala as the place where fear conditioning is encoded.
Neuroscientists previously suspected that both the amygdala and another brain region, the dorsal hippocampus, were where cues get associated when fear memories are formed. But the new work indicates that the role of the hippocampus is to process and transmit information about conditioned stimuli to the amygdala, said Ilene Bernstein, corresponding author of the new study and a UW professor of psychology.
Associative conditioning is a basic form of learning across the animal kingdom and is regularly used in studying how brain circuits can change as a result of experience. In earlier research, UW neuroscientists looked at taste aversion, another associative learning behavior, and found that neurons critical to how people and animals learn from experience are located in the amygdala.
The new work was designed to look for where information about conditioned and unconditioned stimuli converges in the brain as fear memories are formed. The researchers used four groups of rats and placed individual rodents inside of a chamber for 30 minutes. Three of the groups had never seen the chamber before.
When control rats were placed in the chamber, they explored it, became less active and some fell asleep. A delayed shock group also explored the chamber, became less active and after 26 minutes received an electric shock through the floor of the chamber. The third group was acclimated to the chamber by a series of 10 prior visits and then went through the same procedure as the delayed shock rats. The final group was shocked immediately upon being introduced inside the chamber.
The following day the rats were individually returned to the chamber and the researchers observed them for freezing behavior. Freezing, or not moving, is the most common behavioral measure of fear in rodents. The only rats that exhibited robust freezing were those that received the delayed shock in a chamber which was unfamiliar to them.
"We didn't know if we could delay the shock for 26 minutes and get a fear reaction after just one trial. I thought it would be impossible to do this with fear conditioning," said Bernstein. "This allowed us to ask where information converged in the brain."
To do this, the researchers repeated the procedure, but then killed the rats. They then took slices of the brains and used Arc catfish, an imaging technique, which allowed them to follow the pattern of neural activation in the animals.
Only the delayed shock group displayed evidence of converging activation from the conditioned stimulus (the chamber) and the unconditioned stimulus (the shock). The experiment showed that animals can acquire a long-term fear when a novel context is paired with a shock 26 minutes later, but not when a familiar context is matched with a shock.
"Fear learning and taste aversion learning are both examples of associative learning in which two experiences occur together. Often they are learned very rapidly because they are critical to survival, such as avoiding dangerous places or toxic foods," said Bernstein.
"People have phobias that often are set off by cues from something bad that happened to them, such as being scared by a snake or being in a dark alley. So they develop an anxiety disorder," she said.
"By understanding the process of fear conditioning we might learn how to treat anxiety by making the conditioning weaker or to go away. It is also a tool for learning about these brain cells and the underlying mechanism of fear conditioning."
reference:
Functional Imaging of Stimulus Convergence in Amygdalar Neurons during Pavlovian Fear Conditioning.
Sabiha K. Barot, Ain Chung, Jeansok J. Kim, Ilene L. Bernstein.
PLoS ONE, 2009; 4 (7): e6156 DOI: 10.1371/journal.pone.0006156
Link to PLoS ONE abstract
Swine Flu Testing
Phil Serafino and Kristen Hallam for Bloomberg News (July 7, 2009)
WHO to Recommend Countries Stop Testing All Flu Cases
The World Health Organization will recommend that countries stop trying to test all suspected cases of swine flu, said Keiji Fukuda, the agency’s assistant director-general of health security and environment.
Nations that have reported pandemic flu cases should focus on diagnosing patients by their symptoms, Fukuda said today on a conference call with reporters. That will free up laboratories to test samples in unusual or severe cases, clusters of illnesses and cases with odd symptoms, he said.
“What countries ought to do is tailor down their testing,” he said. “It will ease the burden on labs and make testing less of a chore. It is very hard to keep up.”
The Geneva-based United Nations health agency will continue recommending testing in countries that haven’t reported any cases of the pandemic H1N1 flu virus, Fukuda said. The WHO will release updated guidance on testing within a few days, he said. More than 98,000 pandemic flu cases have been reported worldwide, Fukuda said.
Subscribe to:
Posts (Atom)
