Bill Gates on Insanity and Energy R&D

The U.S. government is "crazy" when it comes to funding for energy research and development, according to high-tech titan Bill Gates. "It's crazy how little we are funding this energy stuff," Gates today told an audience at a U.S. Department of Energy (DOE) conference near Washington, D.C. "Funding for energy [research] in the U.S. is underfunded by a factor of two."

Gates, a founder of Microsoft and the Bill & Melinda Gates Foundation in Seattle, Washington, was a featured speaker at the DOE's Energy Innovation Summit, designed to highlight the work of the Advanced Research Projects Agency-Energy (ARPA-E), which aims to move new energy technologies from the lab bench to the market. For nearly an hour, Gates discussed energy challenges with DOE Secretary Steven Chu in an informal "fireside chat" moderated by John Podesta, former chief of staff to President Bill Clinton and now chair of the Center for American Progress, in Washington, D.C .

Gates's call for increased spending on energy R&D echoed recommendations he made late last year as a member of a blue-ribbon panel of U.S. business leaders convened by the Washington-based American Energy Innovation Council. That group noted that the U.S. government spent about $5 billion on energy research in 2010, compared with about $30 billion for medical research and over $80 billion for defense R&D.

It is "likely that underfunding is delaying the rate of progress," in developing new, cleaner energy technologies, Gates argued. And he isn't discouraged by the idea that some taxpayer money may go to ventures that don't pan out. "The failure rate is going to be very high," perhaps even 90%, he predicted. But "this is a very complex set of technologies, [and] we need literally thousands of companies trying these things so we will get the 10 or 20 approaches we need to make progress."

New, cheaper energy sources are also key to improving the lives of the world's poorest 2 billion people, Gates added: "Without advances in energy, they stay stuck where they are." He also called for the U.S. government to tax or put a price on carbon emissions in order to encourage private investment in clean energy and curb climate change. "If you look at who will be the victims of climate change, it will be small holder farmers [in equatorial nations] … and that brings you back to energy."

Not surprisingly, Chu didn't disagree with Gates. But "I'm not going to use the 'T' word," he joked, referring to Gates' call for using tax policy to create incentives for investments in clean energy. But Chu said the government does need to send clear signals to the private sector, such as those sent by setting high goals for improving vehicle fuel efficiency. "When that went through, the auto companies said: 'OK, now we need to have a game plan,' " Chu noted, adding that "the signal doesn't have to be big, but it needs to be clear."

Attack on Radiation Geneticists Triggers Furor

Allegations that two radiation geneticists suppressed scientific evidence over 60 years ago have triggered a fierce debate among scientists and historians of science. At stake is the legacy of two towering figures in the field, both of them long dead: Hermann Muller, who won the 1947 Nobel Prize in physiology medicine, and Curt Stern, with whom Muller collaborated on several key studies.
The allegations come from Edward Calabrese, a toxicologist at the University of Massachusetts, Amherst. In two recent papers, Calabrese concludes that Muller and Stern downplayed evidence that very low levels of radiation might be harmless, and he contends that Muller knowingly misrepresented the scientific state of the art in his Nobel acceptance speech in Stockholm. Those distortions, Calabrese says, are still affecting risk calculations today.

The broadside has outraged supporters of the two scientists. "Calabrese makes some scurrilous accusations, he accuses a dead man, [Muller] of being a liar. That's character assassination," says James Schwartz, who wrote about Muller in his book In Pursuit of the Gene: From Darwin to DNA. "Muller had a reputation for being a scientist of the utmost integrity."

The work of Muller and Stern laid the foundation for current regulations on radiation safety. Both were members of a U.S. National Academy of Sciences panel that wrote the first report on Biological Effects of Atomic Radiation (BEAR I) in 1956. That report provided a paradigm that still dominates today and has led to the stringent limits on low-dose radiation exposure currently in effect.

Calabrese is best known for his work on hormesis, the hypothesis that most if not all chemicals at low doses are actually good for you. He also says a bit more radiation than the natural background would be healthy for humans: "I believe we live in a radiation-deficit environment."

But current regulations on radiation exposure are based on a so-called linear no-threshold model, which says the effect is proportional with the dose—even at extremely low exposures. Calabrese says he got interested in Muller and Stern when he wanted to find out exactly how that model became so dominant after World War II. His research, published in September issue Archives of Toxicology and the October issue of Environmental and Molecular Mutagenesis, led him back to the BEAR I report, and ultimately to the studies that underpinned it. He spent years digging through the archives of the American Philosophical Society and read Muller's and Stern's correspondence to retrace how the scientific consensus arose.

The field has its origins in 1927, when Muller discovered that x-rays caused mutations in male fruit fly germ cells, which led him to voice concerns about the use of x-rays in medicine. He also started investigating the dose-response relationship of radiation and found that the evidence pointed in the direction of a linear relationship. Conventional wisdom in those days held that most toxic chemicals are harmless at low doses and that everything depends on the dose; as Paracelsus had put it, "Poison is in everything, and no thing is without poison."

Studies in the 1930s and '40s confirmed the linear relationship at intermediate and high doses of radiation. But questions about lower doses remained, in part because the studies were extremely cumbersome; to rack up enough mutations to reach statistical significance, scientists had to expose tens of thousands of flies to ionizing radiation.

In 1946, when Muller won the Nobel for his work, he was a consultant on two major studies funded by the Atomic Energy Commission that sought to answer the low-dose question. Both were led by Stern, then a professor of genetics at the University of Rochester. Calabrese says Muller "guided the group on breeding practices, data interpretation, and manuscript refinement."

The first of the studies, conducted by Stern and Warren Spencer, supported a linear relationship at low doses. But in August 1946, a month before Muller was awarded the Nobel, the results of the second study, which Stern had done with Ernst Caspari, became available. That work showed that flies exposed to similarly low doses of radiation didn't have significantly more mutations than control flies, supporting a "threshold model," in which radiation is innocuous below a certain level.

Muller received the manuscript of the Stern-Caspari study before he went to Stockholm for his Nobel lecture, and on 12 November 1946 he sent Stern a letter in which he wrote:

However, I see that it [the Caspari paper] is very important and shall do all I can to go through it in a reasonable time, surely before I leave again early in December. I hope that Caspari can wait that long if necessary. In the meantime I wonder whether you are having any steps taken to have the question tested again, with variations in technique. It is of such paramount importance, and the results seem so diametrically opposed to those which you and the others have obtained, that I should think funds would be forthcoming for a test of the matter.

Apparently he had not read the entire manuscript but was aware that it contradicted the no-threshold model, says Calabrese—and yet in his speech in Stockholm, Muller felt confident enough to say that there is "no escape from the conclusion that there is no threshold." "It was a misleading and dishonest statement that Muller made," Calabrese says. (A press release from his university about the papers bluntly says that "Muller knowingly lied.")

Schwartz says that conclusion is totally out of proportion. "Muller ... had 10 years of extensive experience in radiation genetics. To expect him to make an acknowledgement of this unpublished manuscript in his Nobel Prize address is the height of hypocrisy, it is totally absurd."
Kenneth Muller, a grandson of the Nobelist who's a professor of physiology and biophysics at the University of Miami, defended his grandfather as well in a recent story in The Chronicle of Higher Education. But in the same story, John Beatty, a professor of history and philosophy of science at the University of British Columbia in Canada who has studied Muller's career, agrees that given the paucity of data, Muller may have been too confident about the linear model. "How could Muller be so sure?" Beatty asks.

In the second paper, Calabrese aims to show that the Stockholm remarks were part of a broader pattern. He contends that Muller and Stern were biased by their post-war anxieties about radiation and tried to downplay the evidence for a threshold model in their handling of the Spencer-Caspari manuscript and later in the influential BEAR I report.

The Stern-Spencer and Stern-Caspari studies were both published in 1948 in the same issue of the journal Genetics, of which Stern was the editor at the time. Calabrese says that for a variety of methodological reasons, the Stern-Caspari study, which yielded evidence that radiation isn't harmful below a low threshold, was the superior one. Yet in the paper, Stern and Caspari seem to stress that the results could be just a statistical fluke, Calabrese says. "They say: 'don't accept our results unless you can explain why they differ from the Spencer paper.' "

Calabrese also discovered that a sentence mentioning the "possibility of a tolerance dose for radiation" appeared in the manuscript, but not in the published paper. He sees that as evidence that Stern, with the consent of Muller, suppressed scientific evidence. "With removal of this conclusion and the cautions about the differences, the paper was acceptable for Muller," Calabrese says.

To Schwartz, the accusations are way over the top. "They openly published their results and in the published paper they freely acknowledge the results," he says. Despite the deletion, the paper still contains a mention that the results point in the direction of a threshold. And it's not strange for Stern to be cautious about Caspari's results. "The Spencer results were entirely consistent with all the previous results. ... The Caspari results were unexpected and therefore Stern and Muller decided they had to be replicated."

Elof Axel Carlson, a former student of Muller who published a biography about him in 1981, is furious about the assault on his mentor. "Muller was enormously conscientious about the accuracy of the work he read," he wrote in an e-mail to Science.

After the two 1948 papers, Stern hired a young new researcher, Delta Uphoff, to do three new studies. The key outcomes were presented and compared with the previous two in a one-page Technical paper in Science in 1949. All three of the new studies appear to support the no-threshold model, although the authors acknowledged that "a final interpretation of the results cannot be offered," in part because in two of the new studies, control flies that received no radiation at all had unusually low mutation numbers, thereby inflating the apparent effects of exposure. The authors promised to publish full data on the three new studies later, but that never happened.

Despite its shortcomings, the Science paper had a major impact on the further development of the field, says Calabrese. It was cited in an influential 1957 review on leukemia and radiation by future Nobelist Edward Lewis in Science that promoted the linear model, as well as the BEAR I report, which concluded that "there is no minimum amount of radiation dose which might be exceeded before any harmful mutations occur." Calabrese says the report was a defining moment when the threshold model was replaced by the linear model as the standard in risk assessment. Within a few years, the new paradigm would be adopted all over the world.

Critics say that Calabrese's view may be colored by conflicts of interest. On his Web site, Carlson calls it "bothersome" that Calabrese's research is funded by chemical companies and the nuclear industry. Calabrese counters that around 80% of his funding comes from the government, that he is transparent about his sponsors, and that he does not consult for them.

Schwartz also notes that Calabrese has an intellectual bias, in that he's pushing the hormesis theory, which Schwartz calls "way out there." He points out that Calabrese tried in vain to convince a National Academy of Sciences panel of the benefits of low-level radiation in 2005. "The experts in the committee listened to his evidence and rejected it," says Schwartz.

Schizophrenia and Psychosis

Throughout recorded history, the disorder we now know as schizophrenia has been a source of bewilderment. Those suffering from the illness once were thought to be possessed by demons and were feared, tormented, exiled or locked up forever.
In spite of advances in the understanding of its causes, course and treatment, schizophrenia continues to confound both health professionals and the public. It is easier for the average person to cope with the idea of cancer than it is to understand the odd behavior, hallucinations or strange ideas of the person with schizophrenia.
As with many mental disorders, the causes of schizophrenia are poorly understood. Friends and family commonly are shocked, afraid or angry when they learn of the diagnosis. People often imagine a person with schizophrenia as being more violent or out-of-control than a person who has another kind of serious mental illness. But these kinds of prejudices and misperceptions can be readily corrected.
Expectations become more realistic as schizophrenia is better understood as a disorder that requires ongoing — often lifetime — treatment. Demystification of the illness, along with recent insights from neuroscience and neuropsychology, gives new hope for finding more effective treatments for an illness that previously carried a grave prognosis.
Schizophrenia is characterized by a broad range of unusual behaviors that cause profound disruption in the lives of people suffering from the condition, as well as in the lives of the people around them. Schizophrenia strikes without regard to gender, race, social class or culture.
Delusions and Hallucinations Are Common in Schizophrenia
One of the most important kinds of impairment caused by schizophrenia involves how a person thinks. The individual can lose much of the ability to rationally evaluate his or her surroundings and interactions with others. They often believe things that are untrue, and may have difficulty accepting what they see as "true" reality.
Schizophrenia most often includes hallucinations and/or delusions, which reflect distortions in the perception and interpretation of reality. The resulting behaviors may seem bizarre to the casual observer, even though they may be consistent with the schizophrenic's abnormal perceptions and beliefs.
For instance, someone with schizophrenia may act in an extremely paranoid manner — purchasing multiple locks for their doors, always checking behind them as they walk in public, refusing to talk on the phone. Without context, these behaviors may seem irrational or illogical. But to someone with schizophrenia, these behaviors may reflect a reasonable reaction their false beliefs that others are out to get them or lock them up.
Nearly one-third of those diagnosed with schizophrenia will attempt suicide. About 10 percent of those with the diagnosis will commit suicide within 20 years of the beginning of the disorder. Patients with schizophrenia are not likely to share their suicidal intentions with others, making life-saving interventions more difficult. The risk of depression needs special mention due to the high rate of suicide in these patients. The most significant risk of suicide in schizophrenia is among males under 30 who have some symptoms of depression and a relatively recent hospital discharge. Other risks include imagined voices directing the patient toward self-harm (auditory command hallucinations) and intense false beliefs (delusions).
The relationship of schizophrenia to substance abuse is significant. Due to impairments in insight and judgment, people with schizophrenia may be less able to judge and control the temptations and resulting difficulties associated with drug or alcohol abuse.
In addition, it is not uncommon for people suffering from this disorder to try to "self-medicate" their otherwise debilitating symptoms with mind-altering drugs. The abuse of such substances, most commonly nicotine, alcohol, cocaine and marijuana, impedes treatment and recovery.
The Onset of Schizophrenia
The onset of schizophrenia in most people is a gradual deterioration that occurs in early adulthood — usually in a person's early 20's. Loved ones and friends may spot early warning signs long before the primary symptoms of schizophrenia occur. During this initial pre-onset phase, a person may seem without goals in life, eccentric and unmotivated. They may isolate themselves and remove themselves from family situations and friends. They may stop engaging in other activities that they also used to enjoy, such as hobbies or volunteering.
Warning signs that may indicate someone is heading toward an episode of schizophrenia include:

• Social isolation and withdrawal
• Irrational, bizarre or odd statements or beliefs
• Increased paranoia or questioning others' motivations
• Becoming more emotionless
• Hostility or suspiciousness
• Increasing reliance on drugs or alcohol (in an attempt to self-medicate)
• Lack of motivation
• Speaking in a strange manner unlike themselves
• Inappropriate laughter
• Insomnia or oversleeping
• Deterioration in their personal appearance and hygiene

While there is no guarantee that one or more of these symptoms will lead to schizophrenia, a number of them occurring together should be cause for concern, especially if it appears that the individual is getting worse over time. This is the ideal time to act to help the person (even if it turns out not to be schizophrenia).

Preventing Back Pain Among New Moms

Back pain is common among new moms, who always seem to be lifting and carrying their newborns.
The American Academy of Orthopaedic Surgeons offers these suggestions to help new mothers thwart back pain:

• Start exercising in short bursts as soon as you can after you give birth.
• Make an effort to get back to your pre-pregnancy weight within six weeks of delivery.
• When you pick up your baby, don't twist your body. Hold baby close to you. Bend at the knees, squat down and lift with your legs.
• Carry baby with a front carrier; never carry baby on your hip.
• Nurse baby in an upright chair. Bring baby to your breast, rather than bending over.
• When putting baby in a car seat, kneel in the backseat, rather than standing upright outside the car.

Sleeping Pills Linked to Raised Risk of Death, Cancer: Study

Prescription sleeping pills may help you get some much needed rest at night, but using them routinely might also make it more likely that you will die or develop certain types of cancer, research suggests.
A new study suggests that those who take these medications are four times more likely to die than people who don't take them. What's more, the research shows that sleeping pill use is also associated with a raised risk for certain cancers. The findings appear online Feb. 27 in the journal BMJ Open.
Sleeping pills linked to these risks included benzodiazepines such as temazepam; non-benzodiazepines such as Ambien (zolpidem), Lunesta (eszopiclone) and Sonata (zaleplon); barbiturates; and sedative antihistamines.

The new study only shows an association between the sleeping aids and death risk, not cause-and-effect, and many experts are urging caution in jumping to any conclusions from the findings.
The study author, however, was less reticent.

"Popular sleeping pills are associated with a shocking excess of deaths and a horrible increase in new cancers," said Dr. Daniel Kripke, of the Scripps Clinic Viterbi Family Sleep Center, in La Jolla, Calif.
Many Americans use sleeping pills. During 2010, between one in 20 and one in 10 adults took a sleeping pill in the United States.

In the new study, Kripke's team tracked more than 10,500 people averaging 54 years of age. These patients had a range of underlying health conditions and were prescribed sleeping pills for an average of about 2.5 years between 2002 and 2007. The researchers compared these patients' risks for death and cancer against those of people who did not take sleeping pills.

Those who were prescribed up to 18 doses a year were 3.6 times more likely to die than their counterparts who were prescribed none, while those prescribed between 18 and 132 doses were more than four times as likely to die, the study showed. Those taking more than 132 doses a year had five times the risk of dying compared to those prescribed none. This was true regardless of age, but risks were highest among those individuals aged 18 to 55.

Specifically, there were 265 deaths among 4,336 people taking Ambien, compared with 295 deaths among the 23,671 people who had not taken sedatives or sleeping pills.

Those taking the highest doses were also at greater risk of developing several types of cancer, including esophagus, lymphoma, lung, colon and prostate cancers. Interestingly, the risks of leukemia, breast cancer, uterine cancer, bladder cancer, leukemia and melanoma were not elevated. This association was not explained away by preexisting health problems, the researchers added.

There are many known mechanisms that may explain these increased risks, Kripke stressed. For example, esophageal regurgitation may lead to esophageal cancer. These medications may also make sleep apnea worse, and they may make people more susceptible to falls and automobile crashes.
"For the particular sleeping pills studied, I do not see any time I would prescribe them," Kripke said.
However, other experts weren't ringing alarm bells.

Dr. Victor Fornari, director of child and adolescent psychiatry at the Zucker Hillside Hospital of the North Shore-Long Island Jewish Health System in Manhasset, N.Y., said that people who take sleeping pills should not panic. There could be many reasons for this increased risk of death that have little to do with the pills and more to do with the reasons why people take them, he explained.

"Sleep is the first thing affected when someone is under distress due to medical illness or psychological problems," he pointed out. "These are safe and effective medications when prescribed by a physician as part of a comprehensive treatment plan."

"Don't stop taking these medications if you feel that you need them and are taking them with a doctor's prescription, but be mindful that they shouldn't be taken frivolously and there are alternatives such as avoiding napping, getting proper exercise, eliminating caffeine and doing other the kinds of things that improve sleep hygiene," Fornari said.

But Dr. Bryan Bruno, acting chairman of the department of psychiatry at Lenox Hill Hospital in New York City, cautioned against the chronic use of sleeping pills.

"They can be dangerous and are ideally used on a temporary or short-term basis," he said. "Chronic use should be avoided if possible, particularly because there are risks involved, including dependence. They are not benign or without risk, and should be used cautiously."

More information
Daniel F. Kripke, M.D., Scripps Clinic Viterbi Family Sleep Center, La Jolla, Calif.; Bryan Bruno, M.D., acting chairman, department of psychiatry, Lenox Hill Hospital, New York City; Victor Fornari, M.D., director, child and adolescent psychiatry, Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Manhasset, N.Y.; Feb. 27, 2012, BMJ
http://www.sleepfoundation.org/article/sleep-topics/healthy-sleep-tips 

Pediatricians Renew Call for HPV Vaccine for Boys

The American Academy of Pediatrics on Monday renewed its call that all boys ages 11 and 12 receive the three-dose vaccine for the human papillomavirus (HPV).

The HPV vaccine has been available and recommended for girls and young women since 2006, because it's highly effective at preventing cervical cancer. Since then, other cancers thought to be caused by HPV have increased, including anal cancer and some head and neck cancers.

"Initially, when HPV vaccines were being evaluated, there was an assumption that they would be for preventing cervical cancer and genital warts. Subsequent to that, some things have occurred that show us that providing the vaccine to both genders would be beneficial," Dr. Michael Brady, chairman of the academy's Committee on Infectious Diseases, told HealthDay.

"Currently, our approach isn't effective from a public health perspective since males are also participants in the transmission of HPV. If we include both girls and boys, we could have a potential impact on HPV transmission," added Brady, also physician-in-chief at Nationwide Children's Hospital in Columbus, Ohio.

The new guidelines, published online Feb. 27 in the journal Pediatrics, mirror a recommendation released last October by the U.S. Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

The HPV virus can cause cervical, anal and some head and neck cancers, as well as genital warts, according to the CDC. The virus is transmitted though genital or oral sex, and many people who have the virus don't know they have it. To be effective, the vaccine for the virus must be given before someone is ever infected. That's why health experts recommend giving it in the preteen years of 11 or 12.

"I understand most parents aren't interested in hearing about their children being sexually active, but this is a cancer vaccine that's given for a number of different reasons that has to be given prior to the onset of sexual activity," Brady said, adding that another reason to give the vaccine at a younger age is that studies have shown the immune system responds more strongly to the vaccine at this age. "Children between 9 and 12 get the best response to this vaccine," he explained.

He cautioned that the vaccine doesn't protect against all sexually transmitted diseases. Whether vaccinated against HPV or not, practicing safe sex is still crucial for preventing potentially life-threatening infections.

"Plus, if you give HPV vaccine only to females, you won't have any impact for men who have sex with men. By expanding the vaccine to both genders, we would reduce the overall transmission of HPV. And, we would make sure all of the complications of HPV would be prevented in both genders," said Brady.

Brady noted that this vaccine is quite safe, with the most significant side effect being transient soreness in the vaccinated arm. "This vaccine has very minimal risk," he said. However, he said any time you give children in this age group a vaccination or take their blood, they are more likely to faint than people in other age groups. For this reason, your child will be asked to sit for 15 minutes or so after getting the vaccine to make sure that doesn't happen.

One vaccine expert agreed with the new recommendation.

"What the AAP is doing is being consistent with the [CDC] recommendations. There will be a benefit to women from immunizing men, as well as the prevention of warts in males, and possibly cancer associated with HPV," said Dr. Kenneth Bromberg, director of the Vaccine Research Center at the Brooklyn Hospital Center in New York City.

Both experts said that by providing the vaccine to girls and boys, the vaccine might become less controversial. And, because the CDC recommends it, both said that insurance coverage likely wouldn't be an issue. The three-shot regimen costs approximately $360.

SOURCES:
Michael T. Brady, M.D., chairman, American Academy of Pediatrics' Committee on Infectious Diseases, and physician-in-chief, Nationwide Children's Hospital, Columbus, Ohio; Kenneth Bromberg, M.D., chairman, pediatrics, and director, the Vaccine Research Center, The Brooklyn Hospital Center, New York City; Feb. 27, 2012, Pediatrics, online

Stents No Better Than Medicine for Stable Heart Disease, Study Says

Many people with stable heart disease undergo an expensive artery-opening procedure when medication would work just as well, a new study suggests.

The procedure involves placing a tiny mesh stent, or tube, in a clogged artery. As many as three-quarters of these operations are unnecessary, said lead researcher Dr. David L. Brown, a professor of medicine at Stony Brook University Medical Center in New York.

Money is the driving force, Brown said. "Everybody gets paid to put in stents, the hospital gets paid, the doctor gets paid, the stenting company gets paid," he said. "It's how our fee-for-service environment has taken over the decision making of this branch of cardiology."

Stenting costs an average of $9,500 more to the patient over a lifetime compared with medication, Brown said. Although the procedure, called percutaneous coronary intervention, reduces death and future heart attacks for someone actually having a heart attack, its use in stable heart disease patients is questionable, he noted.

For the study, published Feb. 27 in the Archives of Internal Medicine, Brown and Dr. Kathleen Stergiopoulos, an associate professor of clinical medicine at Stony Brook, analyzed eight trials involving more than 7,000 patients randomly assigned to medical therapy or stenting plus medication. The trials were begun between 1997 and 2005.

In this type of study, called a meta-analysis, researchers look for patterns that might not have been the main intent of the individual trials.

During an average follow-up of more than four years, no significant differences were seen in longevity or quality of life.

Overall, 649 patients died, 322 who received stents and 327 who received medication alone, the study found. Nonfatal heart attacks were suffered by 323 patients with stents and 291 taking only medication.
Among those with stents, 774 needed new procedures to open blocked heart arteries. Among those on medical therapy, 1,049 also needed a procedure to open blocked arteries.

Of more than 4,000 patients for whom data on chest pain -- called angina -- was available, 29 percent of those with stents had persistent chest pain compared with 33 percent of those on medical therapy alone, Brown found.

There is no data that stenting patients with stable heart disease reduces the risk of dying or having a heart attack, Brown said.

"This is not to say no one will need stenting, but only about a third of patients treated initially with medical therapy will need to cross over to stenting," he said.

"People shouldn't blindly agree to have procedures unless the doctor can tell them that there is a documented benefit" in quality or length of life, he said.

Quality of life involves relief of chest pains, he said. If patients on the best medication still have chest pain that is unacceptable to them, stenting becomes appropriate, Brown said.

Medical therapy included aspirin to prevent clotting, beta blockers and ACE inhibitors or angiotensin receptor blockers to control blood pressure, and statins to lower cholesterol, the researchers noted.
"If you go the medical therapy route, it means the patient has to be followed in an outpatient environment to see how they are responding to the medical therapy, and that takes time and effort that doesn't reimburse very well," he said. "That's part of the equation that drives putting in a stent rather than following the patient on medical therapy."

Dr. James Blankenship, a spokesman for the Society for Cardiovascular Angiography and Interventions, wasn't surprised by the study.

"This is largely old news and many interventional cardiologists are avoiding the pitfalls that the authors are pointing out," he said. "In fact, the volume of interventions among Medicare patients has gone down 18 percent between 2005 and 2010."

"For many people, conservative medical therapy is the right thing, but for those who have a lot of symptoms, having a coronary intervention is a reasonable strategy," he said.
Dr. Gregg C. Fonarow, co-director of the University of California, Los Angeles Preventive Cardiology Program at the David Geffen School of Medicine, agreed that medical therapy is the first choice for patients with stable heart disease.

Coronary stenting should be reserved for those patients who have worsening symptoms despite optimal medical therapy, he said.

For patients with stable coronary artery disease, "the most effective and valuable therapy to prevent disease progression, heart attacks, stroke, heart failure and premature cardiovascular death is a combination of medications together with lifestyle modification," Fonarow added.

SOURCES:
David L. Brown, M.D., professor, medicine, Stony Brook University Medical Center, New York;James C. Blankenship, M.D., Geisinger Medical Center Cardiovascular Medicine, Danville, Pa., and spokesman, Society for Cardiovascular Angiography and Interventions;Gregg C. Fonarow, M.D., professor, cardiovascular medicine and science, and director, Ahmanson-UCLA Cardiomyopathy Center, and co-director, University of California, Los Angeles Preventive Cardiology Program, David Geffen School of Medicine; Feb. 27, 2012, Archives of Internal Medicine

Omega-3 Fatty Acids May Protect the Aging Brain

Middle-aged and elderly adults who regularly eat foods rich in omega-3 fatty acids may slow the mental decline that leads to dementia, according to a new study.

Researchers found that people with the highest blood levels of these essential fatty acidsfound in fish such as salmon and tunawere more likely to perform well on tests of mental functioning and to experience less age-related brain shrinkage.

"We feel fatty-acid consumption exerts a beneficial effect on brain aging by promoting vascular health," said the study's lead author, Dr. Zaldy Tan, associate professor at the Easton Center for Alzheimer's Disease Research and the division of geriatrics at the University of California, Los Angeles. This might include reducing blood pressure and inflammation, he added.

Previous research linked dementia risk with the amount of omega-3 fatty acids in blood plasma, which reflects how much people had eaten in the past few days. But in the current work, researchers could estimate the amount of omega-3s that participants had consumed in the past several months by looking at how much had built up in their red blood cells.

"This represents their average intake of fatty acids, not just a snapshot," Tan said.

The study, published in the Feb. 28 issue of the journal Neurology, did not prove that omega-3 fatty acids prevent mental decline, merely that there may be an association between consumption of fatty acids and brain health.

For the study, researchers measured the red blood cell level of fatty acids in 1,575 dementia-free people whose average age was 67. About three months later, participants underwent mental-functioning tests and MRI scans that examined brain size and blood supply in the brain.

The participants were in the Framingham Offspring Study, which is predominately white. Whether the association would apply to other ethnic and racial groups needs to be explored, the authors said.
The researchers found that those with the lowest levels of omega-3s had worse scores on tests of visual memory, attention and abstract thinking than people who ranked in the top 75 percent for fatty-acid levels.

Adults in the bottom 25 percent also tended to have smaller brain volume overall. The decrease in brain volume was enough to make their brains appear two years older than those of people in the top three-quarters for fatty-acid levels.

Brain scans also showed signs of less blood supply in the brains of people with the lowest omega-3 levels. This suggests they may play a role in promoting general vascular, or blood vessel, health in the brain, similar to how they are thought to help heart health, rather than acting on just one brain area, Tan said.

The researchers took into account various health and lifestyle factors, including age, education and body mass index, to explore whether other differences among the people with low levels of omega-3s could help explain their more rapid brain aging.

But after controlling for those risk factors, "the difference [in brain aging] is still there so we conclude that omega-3 fatty acids likely explain them," Tan said.

Tan added, however, that it remains possible that factors they did not control for, such as fruit and vegetable consumption, are really responsible for the brain benefits. Another possibility is that the slight mental decline that the people in the older brain group were experiencing caused them to eat less healthy omega-3-rich foods, instead of vice versa.

"This is a strengthening of the argument that people with less [omega-3 fatty acids] have higher risk of dementia," said Dr. Nikolaos Scarmeas, associate professor of clinical neurology at Columbia University Medical Center in New York City.

But questions remain over whether fatty-acid levels really influence changes in brain size, Scarmeas added. A clinical trial comparing high and low intake of omega-3s in relation to brain imaging would help answer those questions, he said.

In the meantime, fish is "a good prescription for other things and we have a hint it might be helpful for the brain," Scarmeas said.

That the current study reported a difference in brain health between people with omega-3 fatty-acid levels in the bottom 25 percent and top 75 percent suggests that there is a threshold level of consumption to attain brain gains.

A previous study in which participants filled out food surveys found decreased risk of vascular brain problems among those who ate at least three servings of fish a week.

SOURCES:
Zaldy Tan, M.D., associate professor, Easton Center for Alzheimer's Disease Research and the Division of Geriatrics, University of California, Los Angeles; Dr. Nikolaos Scarmeas, associate professor, neurology, Columbia University, New York City; Feb. 28, 2012, Neurology

'Chemo Brain' May Linger 20 Years After Breast Cancer Treatment

"Chemo brain," the name given to the mental fog and related memory problems that can occur during and after chemotherapy, may last for two decades after breast cancer treatment, new research suggests.
In the new study, 196 women with breast cancer who were treated with chemotherapy roughly 21 years earlier performed worse on tests of their memory, processing speed and other thinking ("cognitive") skills when compared to their counterparts who had never been diagnosed with cancer.
Participants had all been treated for breast cancer with a chemotherapy combination that included the drugs cyclophosphamide, methotrexate and 5-fluorouracil between 1976 and 1995. This regimen was considered the standard of care for breast cancer worldwide from the 1970s to the 1990s and was received by thousands of women during this time. Women in the study were aged 50 to 80.
"To our knowledge, this is the first study to suggest that subtle cognitive deficits may be among the long-term effects of chemotherapy, especially of the earlier regimens," study author Sanne Schagen, a group leader at the department of psychosocial research and epidemiology at the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital in Amsterdam, said in a news release from the American Society of Clinical Oncology.

She added that while the results don't suggest that breast cancer survivors need to be watched more closely for memory and thinking problems, they could guide referrals to support services as needed.
In general, women who received this chemotherapy regimen had lower scores on tests of their ability to recall words, information-processing speed, and coordination of thinking and hand movement, such as putting pegs in a board, than women who did not. The results on these tests were similar to those seen among people who had just completed chemotherapy, and their magnitude was comparable to roughly six years of age-related decline in mental function, the study authors noted.
The researchers also assessed the women for depression and self-reported memory problems as part of the study. The women who had received chemotherapy also had more memory complaints than their peers who did not have chemo, but these complaints were not related to how they performed on memory tests.

The study findings were published online Feb. 27 in the Journal of Clinical Oncology.
Dr. Tim Ahles, the director of the Neurocognitive Research Laboratory at Memorial Sloan-Kettering Cancer Center in New York City, said this new study is the first to illustrate that long-term breast cancer survivors are still experiencing difficulty with their thought processes. "It adds to the notion that these effects may be long term and permanent," he said.

The effects of so-called chemo brain vary from person to person, and not all people who receive chemotherapy will develop or be affected by these issues.

"If someone is a professional who has an extremely demanding job, even a small change may be problematic, whereas for someone who is retired and has a more relaxed lifestyle, it may be less of a problem," Ahles said. "For women who are newly diagnosed and looking at treatments, it is still important to know that not everyone experiences these deficits."

In terms of prevention and treatment, there are more questions than answers right now. "This is an active area of research, and now that we have identified this is a real problem, people are turning their attention to what we can do to help treat and reduce some of the negative impact," Ahles noted.
Dr. Marisa Weiss, president and founder of Breastcancer.org and director of breast radiation oncology and breast health outreach at Lankenau Medical Center in Wynnewood, Pa., said the new study "shows only a few pieces of this complex puzzle."

She said it wasn't clear whether subtle losses in mental function were due to cancer alone, the effects of other therapies such as anti-estrogen treatments, or other factors.

Although the study uncovered an association between the cancer treatment and memory problems in the study patients, it did not prove a cause-and-effect relationship.

"There were many differences between these two groups," Weiss said, including whether or not they underwent the specific chemotherapy regimen. "We still need to fill in the other puzzle pieces before we can see what the picture is going to look like."

Dr. Stefan Gluck, a professor in the department of medicine and assistant director of the University of Miami/Sylvester Comprehensive Cancer Center, said that the new findings confirm this is not a temporary problem. "It may be the combination of drugs used 20 years ago were more likely to cause these issues," he said. "Today's drugs may be less likely to cause long-term cognitive effects."
He also added that drugs taken by many breast cancer survivors to stave off a breast cancer recurrence after treatment may also contribute to chemo brain.

SOURCES:
Tim Ahles, Ph.D., director, Neurocognitive Research Laboratory at Memorial Sloan-Kettering Cancer Center, New York City; Stefan Gluck, M.D., professor, department of medicine and assistant director, University of Miami/Sylvester Comprehensive Cancer Center; Marisa Weiss, president and founder, Breastcancer.org and director, breast radiation oncology and breast health outreach, Lankenau Medical Center, Wynnewood, Pa.; Feb. 27, 2012, Journal of Clinical Oncology, online

Monitoring Spinal Cord During Certain Surgeries May Prevent Complications

The spinal cord should be monitored during spinal surgery and certain chest surgeries -- such as procedures to repair narrowing of the walls of the aorta -- to help prevent paralysis or loss of muscle function, says an updated guideline from the American Academy of Neurology.
Continuous assessment of the spinal cord during surgery (intraoperative monitoring) can alert surgeons in time to find and correct problems before spinal cord damage occurs.
Monitoring detects small changes in nerve-signal transmission throughout the surgery.
"Paraparesis [partial paralysis of the legs], paraplegia and quadriplegia are potential serious complications of surgeries where the spinal cord is at risk," guideline lead author Dr. Marc Nuwer, of the University of California, Los Angeles, said in an academy news release.
"Monitoring can help prevent damage by identifying problems early enough to allow for interventions. If intraoperative monitoring raises warnings, surgeons and anesthesiologists can modify the surgery to reduce the risk of these complications," he noted.
The guidelines appear in the Feb. 21 issue of the Neurology and also in the Journal of Clinical Neurophysiology.
"The best way to treat paralysis is to prevent it in the first place. Spinal cord monitoring supervised by a neurologist can help meet this goal," Nuwer said.

SOURCE:
American Academy of Neurology, news release, Feb. 20, 2012

Genetically Engineered Bacteria Could Help Fight Climate Change

As humans warm the planet by releasing carbon dioxide into the atmosphere, some researchers believe that capturing CO₂ and trapping it in buried rocks could lower the risk of catastrophic climate change. Now a team of researchers has shown that bacteria can help the process along. They can even be genetically modified to trap CO₂ faster, keeping it underground for millions of years.
When CO₂ is pumped into underground porous rocks, it combines with metal ions in the salty water that fills the rock pores and mineralizes into mineral carbonates, such as calcium carbonate (CaCO₃). The process can take thousands of years. To see if they could speed things up, biochemist Jenny Cappuccio and colleagues at the Lawrence Berkeley National Laboratory's Center for Nanoscale Control of Geologic CO₂ put a diverse mix of common bacterial species in a calcium chloride solution in the lab and then pumped in CO₂. They found that calcium carbonate formed faster in areas where the bacteria were living than it did in sterile solutions. The CaCO₃ also had a different mineral structure when the bacteria were around. It tended to grow into crystals of white calcite instead of amorphous black lumps (see picture). The bacteria enhanced the formation of calcite even when they were just lying around, not growing or multiplying.
Intrigued, the team guessed that the surfaces of the bacteria were somehow helping the CO₂ hook up with calcium ions. To test that idea, they decided to modify one of the bacterial species, Caulobacter vibrioides, shaping its surface to attract calcium ions, and see what happened.
Cappuccio and colleagues inserted a short DNA sequence that coded for a loop of six glutamic acids—a type of amino acid—into C. vibrioides. The loop sticks out of the bacteria's surface protein and is repeated over the entire surface of the bacteria in a hexagonal pattern. Each six-acid loop contains six negative charges. The team reasoned that this "negative loop" could fit neatly around positively charged calcium ions in water, attracting them to the surface of the bacteria and coaxing them to form CaCO₃.
It worked. When the researchers pumped CO₂ into the tanks where the modified bacteria were living, even more CaCO₃ solidified than in tanks with unmodified bacteria. Better yet, more of it was in the crystalline calcite form, which is more stable—and likely to sequester CO₂ over geological time—than amorphous CaCO₃. Cappuccio reports the team's results today at a meeting of the Biophysical Society in San Diego, California.
Robin Gerlach, a biological engineer at Montana State University in Bozeman, who was not involved with the study, calls the work "very fundamental." He anticipates broad applications, including stabilizing soil in flood zones, isolating radioactive isotopes, and identifying early life in the fossil record by tracking changes in carbonate mineralization.
But Cappuccio is the first to admit that the results need to be demonstrated in conditions closer to real life. She wants to test her modified bacteria at higher pressures, higher temperatures, and lower pH, conditions closer to those that might be found underground. Eventually, her team wants to modify hard-to-grow extremophiles—bacteria that grow in very hot, high-pressure environments—that are more like the microorganisms that colonize the underground rock formations where CO₂ would be sequestered.

Dieting Can Prove Dangerous for Kidney Disease Patients

Overweight or obese people with chronic kidney disease may suffer further kidney damage if they use certain weight-loss methods, a new study warns.
Cleveland Clinic researchers analyzed the eating and lifestyle habits of nearly 11,000 overweight or obese adults who took part in the U.S. National Health and Nutrition Examination Survey.
Of those with chronic kidney disease, 50 percent said they had tried to lose weight in the past year, and 8 percent said they used medications as part of their weight-loss program. Some also used weight-loss methods that promoted high-protein diets that called for up to 1.9 grams per kilogram of body weight per day, considerably more than the amount recommended by the National Kidney Foundation.
Patients with chronic kidney disease are advised to consume 0.6 grams to 0.75 grams of protein per kilogram of body weight per day. The typical American adult consumes about 1.2 grams of protein per kilogram of body weight per day. (To convert body weight into kilograms, divide weight in pounds by 2.2.)
Weight-loss medications and high-protein diets are not recommended for people with chronic kidney disease because these methods may lead to further kidney damage, the researchers said in the study, published online recently in the International Journal of Obesity.
"People who are overweight or obese are at higher risk for chronic kidney disease, and there is a great need to define what the appropriate lifestyle changes and weight loss modalities are for protecting kidney function," lead author Dr. Sankar Navaneethan, a nephrologist in the Glickman Urological and Kidney Institute at Cleveland Clinic, said in a clinic news release.
"Rather than using fad diets or diet pills, overweight and obese people with kidney disease may adopt a weight loss plan that incorporates a low-protein, low-calorie diet, regular physical activity and close follow-up by their physicians," Navaneethan added.
The researchers called for further studies to identify safe weight-loss strategies for overweight or obese adults with chronic kidney disease, a condition in which kidney function progressively worsens.
More than 10 percent of adults 20 and older in the United States have chronic kidney disease, according to the U.S. Centers for Disease Control and Prevention.

SOURCE:
Cleveland Clinic, news release, Feb. 21, 2012

Recognizing the Symptoms of Bipolar Disorder

People with bipolar disorder can have a range of symptoms. Many experience dramatic mood swings, going from emotional highs to emotional lows with more normal moods in between, while others have much milder mood changes.

Bipolar Symptoms: Mania
Mania is a term that describes the emotional highs of bipolar disorder. Mania, or a manic episode, is usually characterized by feelings of extreme energy, restlessness, or irritability.
In general, symptoms of a manic episode may include:

• High energy, excessive activity, and/or restlessness
• Overly good mood
• Irritability
• Fast, erratic talking
• Racing thoughts
• Inability to concentrate
• Little need for sleep
• Feelings of power
• Poor judgment
• Reckless spending
• High sex drive
• Alcohol or drug abuse
• Aggression
• Refusal to admit that there is a problem

The severity of manic symptoms can vary in bipolar disorder, and most people will not experience all symptoms. In some forms of bipolar disorder, people will experience hypomania, a milder form of mania that usually feels good. People who are experiencing hypomania often can function well and be more productive than usual. But if left untreated, hypomania can develop into severe mania or can change to depression.
If your elevated or irritable mood is accompanied by manic symptoms most of the day, nearly every day, for at least one week, your doctor may diagnose a manic episode.

Bipolar Symptoms: Depression
In bipolar disorder, manic episodes alternate with periods of emotional lows, which are known as depressive episodes. Signs of a depressive episode may include:

• Sadness, anxiety, or a feeling of emptiness
• Hopelessness
• Feelings of guilt, feeling worthless, or feeling helpless
• Lack of interest in activities that were once enjoyable, such as sex
• Low energy
• Trouble with concentration or memory
• Restlessness or irritability
• Excessive sleeping or insomnia
• Changes in appetite or weight
• Pain or other physical symptoms not explained by an illness or injury
• Thoughts of death, or suicidal thoughts or attempts

A diagnosis of depressive episodes is made if at least five of these symptoms are present for most of the day, nearly every day, for two weeks or longer.

Bipolar Symptoms: Mood Swings
Symptoms of mania and depression can vary dramatically among people with bipolar disorder. All people with bipolar disorder experience mood swings, but the severity of these mood swings can vary.
In the form of bipolar disorder known as bipolar I, there are recurrent episodes of mania and depression. In bipolar II, severe mania never develops, but periods of hypomania alternate with depressive episodes.
The severity and symptoms of bipolar disorder can change over time, and the way the condition is treated may need to change as well.
If you are experiencing mood swings that are disrupting your life, speak to your doctor, who can recommend a mental health professional. Mental health professionals can talk with you about the symptoms, and diagnose and treat bipolar disorder if that is necessary.
Medication and other therapies can help you manage the bipolar symptoms and smooth out the highs and lows that interfere with living a normal, productive life.

College Suicide — Know the Warning Signs

College Suicide: The Warning Signs
Some people may actually be screaming for help, even if they aren’t vocalizing what they're thinking about. Typical signs of depression include:

• Difficulty handling schoolwork
• Disinterest in activities that used to be enjoyed
• Changes in sleeping and eating habits
• Lack of energy or feeling drained
• Emotional outbursts, from crying to being easily irritated

Self-destructive behavior, serious substance abuse, changes in relationships — particularly sexual promiscuity — are all warning signs of serious depression and potential suicidal thoughts that might not typically be recognized.
This kind of behavior "may be rationalized as a normal thing, but in reality it's a sign of somebody who's caught up in hopelessness, despair, and issues of self-esteem," says Kaveh Zamanian, PhD, a clinical psychologist and owner of East End Psychological Associates in Louisville, Ky. "Certainly the most obvious sign is any declaration of hopelessness and thoughts of suicide. Sometimes people say it to minimize it or in jest. My tendency is to take those seriously."
Any mention at all of suicide warrants immediate attention. Don't waste time wondering whether your friend is for real or contemplating if he would go through with it. If he even mentions it, regardless of whether he would follow through, he’s asking for help.

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Related: 10 Ways to Reduce Stress in College

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College Suicide: How to Get Help
Whether you're the individual experiencing these symptoms or you're witnessing a close friend, it's essential to get help now.
Speaking with a mental health professional or counselor is a great first step, says Zamanian. They're trained to help students in this situation. You can also go to your resident adviser or floor supervisor in your dorm.
"Mental health issues have been on the rise," says Zamanian. So college counseling centers are becoming better equipped to deal with these life-threatening situations. They can offer suicide screenings and follow up with appropriate interventions.
"If you're in doubt, I think you should get a consultation from someone," says Zamanian. You can also run it by friends — if you're suspicious, it's likely they are, too. Talk to them about your concerns and get their perspective. They can give you the confidence you need to approach your friend or get help. When it comes to contacting family members, says Zamanian, things get a bit trickier. If you don't know the family situation, involving relatives might not be much help.
A mere thought or passing statement about suicide is a cry for help. Be aware, listen, and get the help that’s needed.

Stem Cell Development Triggers Memory

Researchers at the RIKEN-MIT Center for Neural Circuit Genetics have discovered an answer to the long-standing mystery of how brain cells can both remember new memories while also maintaining older ones.

They found that specific neurons in a brain region called the dentate gyrus serve distinct roles in memory formation depending on whether the neural stem cells that produced them were of old versus young age.

The study will appear in the March 30 issue of Cell and links the cellular basis of memory formation to the birth of new neurons - a finding that could unlock a new class of drug targets to treat memory disorders.

The findings also suggest that an imbalance between young and old neurons in the brain could disrupt normal memory formation during post-traumatic stress disorder (PTSD) and aging. "In animals, traumatic experiences and aging often lead to decline of the birth of new neurons in the dentate gyrus. In humans, recent studies found dentate gyrus dysfunction and related memory impairments during normal aging," said the study's senior author Susumu Tonegawa, 1987 Nobel Laureate and Director of the RIKEN-MIT Center.

Other authors include Toshiaki Nakashiba and researchers from the RIKEN-MIT Center and Picower Institute at MIT; the laboratory of Michael S. Fanselow at the University of California at Los Angeles; and the laboratory of Chris J. McBain at the National Institute of Child Health and Human Development.

In the study, the authors tested mice in two types of memory processes. Pattern separation is the process by which the brain distinguishes differences between similar events, like remembering two Madeleine cookies with different tastes. In contrast, pattern completion is used to recall detailed content of memories based on limited clues, like recalling who one was with when remembering the taste of the Madeleine cookies.

Pattern separation forms distinct new memories based on differences between experiences; pattern completion retrieves memories by detecting similarities. Individuals with brain injury or trauma may be unable to recall people they see every day. Others with PTSD are unable to forget terrible events. "Impaired pattern separation due to the loss of young neurons may shift the balance in favor of pattern completion, which may underlie recurrent traumatic memory recall observed in PTSD patients," Tonegawa said.

Neuroscientists have long thought these two opposing and potentially competing processes occur in different neural circuits. The dentate gyrus, a structure with remarkable plasticity within the nervous system and its role in conditions from depression to epilepsy to traumatic brain injury - was thought to be engaged in pattern separation and the CA3 region in pattern completion. Instead, the MIT researchers found that dentate gyrus neurons may perform pattern separation or completion depending on the age of their cells.

The MIT researchers assessed pattern separation in mice who learned to distinguish between two similar but distinct chambers: one safe and the other associated with an unpleasant foot shock. To test their pattern completion abilities, the mice were given limited cues to escape a maze they had previously learned to negotiate. Normal mice were compared with mice lacking either young neurons or old neurons. The mice exhibited defects in pattern completion or separation depending on which set of neurons was removed.

"By studying mice genetically modified to block neuronal communication from old neurons -- or by wiping out their adult-born young neurons - we found that old neurons were dispensable for pattern separation, whereas young neurons were required for it," co-author Toshiaki Nakashiba said. "Our data also demonstrated that mice devoid of old neurons were defective in pattern completion, suggesting that the balance between pattern separation and completion may be altered as a result of loss of old neurons."

Reference
The work was supported by the RIKEN-MIT Center for Neural Circuit Genetics, Howard Hughes Medical Institute, Otsuka Maryland Research Institute, Picower Foundation and the National Institutes of Health.
RIKEN

A New Design Strategy For The Development Of Vaccines For HIV

HIV has eluded vaccine-makers for thirty years, in part due to the virus' extreme ability to mutate. Physical scientists and clinical virologists from the Massachusetts Institute of Technology (MIT) and the Ragon Institute in Cambridge, Mass., have identified a promising strategy for vaccine design using a mathematical technique that has also been used in problems related to quantum physics, as well as in analyses of stock market price fluctuations and studies of enzyme sequences. The team, led by Arup Chakraborty of MIT and Bruce Walker of the Ragon Institute, will give an update on its work at the Biophysical Society 56th Annual Meeting, held Feb. 25-29 in San Diego, Calif.

Vaccines prime the immune system to target molecular signatures associated with a particular pathogen. But HIV's ability to mutate has made it difficult to identify reliable vaccine targets. In their search for a new type of target, the team from the Ragon Institute did not focus on individual amino acids. Instead, the researchers sought to identify independently evolving groups of amino acids where, within each group, amino acids mutate in tandem (meaning that they rely on one another to maintain the viability of the virus). In particular, they looked for groups of amino acids within which combinations of mutations would have a greater chance of making the virus unviable. By staging a multi-pronged attack against these regions of HIV, the researchers reasoned, they might be able to trap the virus between two bad choices: be destroyed by the immune system, or mutate and destroy itself.

With a mathematical tool called random matrix theory, the team searched for high-order evolutionary constraints in the so-called Gag region of HIV. The researchers were looking for collectively co-evolving groups of amino acids with a high number of negative correlations (meaning multiple mutations would destroy the virus) and a low number of positive correlations (meaning the virus could survive multiple mutations). They found this combination in a region, which they call Gag sector 3, that is involved in stabilizing the protein shell of the virus: too many mutations here, and the virus' structure would collapse.

Interestingly, when the team studied HIV-infected individuals whose bodies are naturally able to fend off the virus' attacks - so-called "elite controllers" - they found that these individuals' immune systems preferentially targeted Gag sector 3 over other proteins.

At the moment, the study authors are working to extend their methods to HIV proteins beyond Gag. The team is also developing elements of the active components of a vaccine that would prime the immune system to selectively target Gag sector 3 proteins. They expect to begin testing in animal models soon.

Reference
Meeting Home Page: http://www.biophysics.org/2012meeting/Main/tabid/2386/Default.aspx
The presentation, "Analysis of collective coevolution in HIV proteins suggests strategies for rational vaccine design," will be presented by Dr. Chakraborty's graduate student Karthik Shekhar at 12:30 p.m. on Sunday, Feb. 26, 2012, in the San Diego Convention Center, Room 24ABC. ABSTRACT: http://tinyurl.com/6sz7kuf
American Institute of Physics

Pig-to-Human 'Superbug' May Be Due to Animal Antibiotics

Researchers who traced the evolution of a potentially deadly antibiotic-resistant bacteria strain that can jump from livestock to humans say their findings highlight the dangers of widespread antibiotic use in animal food production.

The international team of scientists studied methicillin-resistant Staphylococcus aureus CC398, also known as pig MRSA or livestock-associated MRSA, which most often infects people with direct exposure to swine or other livestock.

It's likely that MRSA CC398 originated as an antibiotic-susceptible strain in humans before it jumped to livestock, they said. Once in livestock, MRSA CC398 became a so-called superbug, resistant to two important antibiotics, tetracycline and methicillin, used to treat staph infections.

This resistance is likely caused by the widespread use of antibiotics in livestock to prevent infection and promote growth, said the authors of the study published online Feb. 21 in the journal mBio.
The findings reveal evolution in action, according to Paul Keim, one of the study authors and a professor and director of the Center for Microbial Genetics and Genomics at Northern Arizona University. He is also director of the pathogenic genomics division at the Translational Genomics Research Institute (TGen) in Phoenix.

"The most powerful force in evolution is selection. And in this case, humans have supplied a strong force through the excessive use of antibiotic drugs in farm animal production. It is that inappropriate use of antibiotics that is now coming back to haunt us," Keim said in a university news release.

This strain of MRSA was discovered less than a decade ago but appears to be spreading quickly, according to study lead author Lance Price, a university faculty member and director of the Center for Food Microbiology and Environmental Health at TGen.

"Our findings underscore the potential public health risks of widespread antibiotic use in food animal production," Price said in the news release. "Staph thrives in crowded and unsanitary conditions. Add antibiotics to that environment and you're going to create a public health problem."

SOURCE:
Northern Arizona University, news release, Feb. 14, 2012

Kidney Damage Greatly Raises Diabetics' Risk for Death

People with type 2 diabetes have a higher risk of death than people without the disease, but a new study suggests that if they also have kidney damage their risk of dying is even greater.

In an analysis of 22 studies, researchers from Brigham and Women's Hospital in Boston found that the annual risk of death for people with type 2 diabetes ranged from 0.28 per 100 patient years to 8.24 per 100 patient years. And, in studies with those with more advanced kidney disease, the risk of death was between 5.9 per 100 patient years to 8.24 per 100 patient years.

"It's no surprise that those with kidney disease have a higher mortality risk," said Dr. Vivian Fonseca, president of medicine and science for the American Diabetes Association. "People with type 2 diabetes often don't know they have the disease, and have many years of poor blood sugar control before they're diagnosed. That means they're likely to have nerve damage and visual damage, which make managing kidney disease more complicated."

The current analysis is published online Feb. 21 in the journal Cardiovascular and Cerebrovascular Disease.
There were almost 92,000 people and nearly 7,000 deaths included in the new analysis. All of the studies were randomized clinical trials including people with type 2 diabetes. The trials had to last at least a year to be included.

Overall, there was approximately a 30-fold difference in the annual risk of death across the various trials, suggesting that people with type 2 diabetes are very diverse, and that some people are at much higher risk of complications and death than others.

The researchers found that those with the lowest risk of death were people under the age of 59 with fewer signs of kidney damage.

Those with the highest risk of death were older, had diabetes for a longer period of time (average of about 15 years), had high blood pressure and signs of kidney disease. The authors found that presence of chronic kidney disease was associated with the highest mortality rates.

"This analysis shows that having a high creatinine level is a very high marker for mortality," said Dr. Joel Zonszein, director of the clinical diabetes center at Montefiore Medical Center in New York City.
Creatinine levels indicate the health of your kidneys. The higher this level is, the less effectively your kidneys are working.

Both experts said it's important to try to prevent kidney damage, because the more it progresses, the harder it becomes to control.

Controlling blood sugar and blood pressure levels are essential to keeping the kidneys healthy, Zonszein said.

"I see much less progression to late-stage kidney disease in patients who are treated aggressively for high blood pressure, especially with ACE inhibitors or ARBs. Patients need to get the proper amounts of these medications to bring their blood pressure to normal," he said.

ACE inhibitors and ARBs are two different types of blood-pressure lowering medications.
"We really can slow the progress of kidney disease, but we have to treat patients correctly early in the disease," Zonszein said.
Fonseca agreed. "Do everything you can to prevent late-stage kidney disease. Get good control of your blood pressure and good control of your diabetes. Make sure you have screening for kidney problems," Fonseca said.

Both also agreed that once late-stage kidney disease has set in, it becomes much harder to control blood pressure and other complications. "This group is a huge challenge and we haven't really found the answers yet. We need new therapies for this particular patient population," Fonseca said.

SOURCES:
Vivian Fonseca, M.D., president, medicine and science, American Diabetes Association; Joel Zonzsein, M.D., director, clinical diabetes center, Montefiore Medical Center, New York City; Feb. 22, 2012, Cardiovascular and Cerebrovascular Disease

Hepatitis C Now Kills More Americans Than HIV

Deaths from hepatitis C have increased steadily in the United States in recent years, in part because many people don't know they have disease, a new government report says.

More Americans now die of hepatitis C than from HIV, the AIDS-causing virus, according to 1999-2007 data reviewed by the U.S. Centers for Disease Control and Prevention (CDC). And most of those dying are middle-aged.

"These data underscore the urgent need to address the health threat posed by chronic hepatitis B and C in the United States," said investigator Dr. Scott Holmberg, chief of the Epidemiology and Surveillance Branch in CDC's Division of Viral Hepatitis.

About 3.2 million Americans are infected with hepatitis C, a major cause of liver cancer and cirrhosis, the CDC authors said. An estimated one-half to three-quarters of infected adults are unaware they have the disease, which progresses slowly.

Hepatitis C is spread through injection drug use, from blood transfusions received before routine blood-screening began in 1992, and through sexual contact. In some cases, it passes from mothers to infants.

"Chronic hepatitis is a leading and preventable cause of premature death in the United States," Holmberg said. "Over time, leaving viral hepatitis untreated can lead to costly care and treatments, and lifetime costs can total hundreds of thousands of dollars. However, early detection and intervention can be cost-effective and save lives."

The new study highlights the need to increase hepatitis awareness and the critical importance of testing, Holmberg said. Screening will increase diagnoses and treatment, thereby reducing hepatitis-related deaths, he said.

The report is published in the Feb. 21 issue of the Annals of Internal Medicine.
Using death records from 1999 to 2007, researchers collected data on some 22 million Americans, looking for those who died from hepatitis B, C and HIV.

The investigators found deaths from hepatitis C surpassed deaths from HIV (15,000 from hepatitis C versus 13,000 from HIV). They also found that deaths from hepatitis C and B are mostly among the middle-aged.
"Seventy-three percent of hepatitis C deaths were reported among those 45 to 64 years old," Holmberg said. "As the population living with hepatitis C in the United States -- 66 percent of whom were born between 1945 and 1964 -- has aged and entered a high-risk period of life for hepatitis C-related disease, deaths associated with hepatitis C have increased substantially."

Vaccines exist for hepatitis B, but not for hepatitis C. If current trends continue, by 2030 deaths from hepatitis C are expected to reach 35,000 a year, researchers say.

According to Dr. Eugene Schiff, director of the Center for Liver Diseases at the University of Miami Miller School of Medicine, "the study is important because it documents and authenticates what we knew." But, "what we need right now, particularly for hepatitis C, is routine screening," noted Schiff, who was not involved with the study.

Dramatic changes are under way in the treatment of hepatitis C, he pointed out. Current treatment involves a cocktail of drugs, including antivirals and interferon, which many people cannot tolerate.
In about two years, interferon-free treatment will be available, Schiff said. This means higher cure rates with fewer side effects, which will make treatment tolerable by most patients, he explained.
"What's going to happen is what happened with HIV -- test and treat," Schiff said. "Patients will be given an interferon-free regimen with cure rates approaching 100 percent," he predicted.
Another study in the same journal issue found that the most up-to-date treatment for hepatitis C can cost $60,000, but may be cost-effective, according to Stanford University health policy researchers.
In a study led by Jeremy Goldhaber-Fiebert, an assistant professor of medicine at the School of Medicine, investigators developed a computer model to assess the cost-effectiveness of a new treatment for hepatitis C. Their model showed that for people with advanced disease the cost was justified in terms of results.

The treatment involves use of two drugs called protease inhibitors -- boceprevir (brand name Victrelis) and telaprevir (brand name Incivek) -- in addition to interferon and an antiviral.

While the new treatment is expensive and may cause side effects, it could reduce patients' risks for cancer and liver transplants, thereby avoiding those costly events and possibly helping patients live longer, better lives, the researchers pointed out in a journal news release.

Yet another study in the journal recommends one-time screening of all those born between 1945 and 1965, instead of waiting until symptoms appear.

SOURCES:
Scott Holmberg, M.D., M.P.H., chief, epidemiology and surveillance branch, division of viral hepatitis, U.S. Centers for Disease Control and Prevention; Eugene R. Schiff, M.D., Leonard Miller Professor of Medicine, director, Schiff Liver Institute/Center for Liver Diseases, University of Miami Miller School of Medicine; Feb. 21, 2012, Annals of Internal Medicine

Specific Dietary Goals May Help Diabetics Eat Better

Specific goals can help people with type 2 diabetes improve their dietary habits, according to a new study.

Participants were given a goal to eat either six or eight daily servings of foods with a low glycemic index -- carbohydrates that are digested slowly and are less likely to cause a spike in blood sugar levels than carbohydrates with a high glycemic index.

Most of the participants achieved the eight-serving goal, partly because many of them were already consuming about six servings of low glycemic index foods a day, the Ohio State University researchers said.

During the study, most of the participants also ate about 500 fewer calories a day and added fruits, vegetables, nuts and seeds to their diet. All these foods are on the low end of the glycemic index.
The researchers also found that participants' confidence in being able to meet their goal was a major factor in their ability to reach the goal. Those with more confidence had higher levels of commitment, which increased their likelihood of success.
The study was published in the journal Patient Education and Counseling.

"We ask people to set goals because they motivate action," lead author Carla Miller, an associate professor of human nutrition, said in a university news release. "Telling people to 'go out and do your best' is not effective. It's not specific enough, or targeted enough, or timely."

"But in this context, it's not just a matter of setting a goal. It's deciding what specifically you are going to modify to help you achieve a more healthful diet," she added.

SOURCE:
Ohio State University, news release, Feb. 8, 2012

Gene Might Boost Risk for Obesity

A new animal study suggests that a genetic mutation could put certain people at higher risk for becoming obese if they eat high-fat diets.

At the moment, the practical uses of the research seem to be limited, but physicians could conceivably test people for the mutation and recommend that they avoid certain kinds of diets, said study co-author Dr. Gozoh Tsujimoto, a professor at Kyoto University's department of genomic drug discovery science in Japan. It may also be possible, Tsujimoto said, to eventually give people drugs to combat the effects of the mutation.
If that happens, there would be "a new avenue for personalized health care," Tsujimoto said.
Scientists have been busy studying genetic links to obesity that could make some people more prone to gain extra weight. Two-thirds of Americans are either overweight or obese, the U.S. Centers for Disease Control and Prevention estimates. Excess pounds contribute to a variety of diseases, including heart disease and cancer.

In the new study, researchers looked at the component of the body's internal communication system that plays a role in the regulation of appetite and the production of fat cells.

The investigators found that mice that didn't have the component were 10 percent fatter than other mice when all were fed a high-fat diet. Mice without the component also developed higher intolerance to glucose.

Research conducted in animals does not always translate into humans, and much more research is needed. However, the researchers found that Europeans with the genetic mutation, known as GPR120, were more likely to be obese.

"Our study for the first time demonstrated the gene responsible for diet-induced obesity," Tsujimoto said.

According to Tsujimoto, more than 3 percent of Europeans have the trait. The next step for researchers is to study its prevalence in Japanese, Korean and Chinese people.

What can be done with the knowledge from the study?

Tsujimoto said physicians could advise people with the trait to avoid high-fat diets. A test is available to detect the trait and it costs about $200 in Japan, Tsujimoto said.

While medications could potentially be developed that would reverse the effects of the genetic trait, there are no such drugs now, Tsujimoto added.

Ruth Loos, director of Genetics of Obesity and Related Metabolic Traits at Mount Sinai School of Medicine in New York City, said "these findings provide another piece of what turns out to be the very large puzzle that describes the causes of obesity."

Consistent findings in mice and humans have put the trait "more firmly on the obesity map and provides a new starting point for more research into the function of this gene," said Loos.

"This is only the beginning of likely many years of research to disentangle the physiological mechanisms that lie behind the link between this gene and obesity risk," she said. "It is only when we understand the physiology and biology better that one can start thinking of developing a drug."

The study appears online Feb. 19 in the journal Nature.
SOURCES:
Gozoh Tsujimoto, M.D., Ph.D., professor, department of genomic dru

Lupin’s bio arm may launch cancer drug this year

Lupin Ltd's biotechnology division hopes to hit the market with its first biotechnology-based cancer drug in India this year, if it gets regulatory approval for clinical trials on time .

“We have conducted two sets of clinical trials for the drug and are awaiting approval for the third trial which should be completed within six months of getting the approval. It will take us another six months for the commercial launch,” Mr Cyrus Karkaria, president of Lupin's biotechnology division, told media persons on the sidelines of the Bio-Asia meet here.

The company is conducting the clinical trials at different centres across the country.

New biotech drugs

It has in the pipeline six more bio-technology based drugs, three of which are undergoing clinical trials; one will undergo clinical trials this year and the remaining two are in the pre-clinical stage. These mainly deal with oncology and inflammation therapeutic areas.

Mr Karkaria pointed out that bio-technology based drug research was more complicated than small molecules and needed significantly more investments. He also felt that the regulatory mechanism could be made simpler , which would help companies launch products at a faster pace.

The company, which has a research-cum-manufacturing facility near Pune, will consider setting up a new manufacturing facility once the products hit the market and gains critical mass in terms of demand. ‘We may initially set up a single train facility at a cost of about $20 million. We are on the look-out for land near our existing facility. Till then, our existing facility will cater to market,” Mr Karkaria said.

The current biotechnology drugs market globally is estimated at between $120 billion and $140 billion. Emerging markets account for a one-fifth share. The domestic market for this category of drugs is expected to touch $2 billion by 2015.

Tarsiers Communicate in Secret Speech

Meet the world's tiniest cryptographers. Philippine tarsiers (Tarsius syrichta), primates native to Southeast Asia that are often no bigger than a human hand, pass messages using an unbreakable code: ultrasonic sounds. A new study shows that these tree-dwellers emit squeaky calls well above the vocal range of any known monkey or ape, perhaps to dodge eavesdropping predators.

Like any good code, ultrasound works because it's rarely used. Few land mammals—bats and kittens are exceptions—coo or call at frequencies above the normal range of human hearing (about 20 kilohertz). That's largely because ultrasonic waves, unlike other sound waves, spread out quickly; that makes it harder for animals to pinpoint the locations of faraway calls, says study co-author Marissa Ramsier, an anthropologist at Humboldt State University in Arcata, California.

The first clue that tarsiers use ultrasound came from observing an odd behavior. The big-eyed, nocturnal creatures occasionally open their mouths as if ready to shout, but no sound humans can hear comes out. On a whim, co-author Sharon Gursky-Doyen, a biological anthropologist at Texas A&M University in College Station, brought a microphone used for recording bat chirps to a Philippine jungle frequented by the primates. The animals, it turns out, are boisterous—just not to human ears. "Philippine tarsiers have often been described as quiet," Ramsier says. But "they're screaming and talking away, and we just didn't know it."

To dig deeper into tarsier communication, Ramsier and colleagues trapped and sedated six tarsiers in the wild. Using a technique first employed to test hearing in newborn babies, the team monitored the brainwaves of the dozing creatures as noises played on a speaker. The primates, the group reports online today in Biology Letters, could register sounds up to 90 kilohertz (slowed down in the accompanying audio), double the upper limit of any primate studied to date.

The team also listened in on the nighttime back and forth between tarsiers. Their calls closely resembled the vocalizations of similar primates: dominated by a single tone followed by several trills. Except they were much higher, fluctuating around 70 kilohertz.

Tarsiers use their savvy for hearing and speaking in ultrasound to eat and to keep from being eaten, Ramsier suggests. The primates dine exclusively on small insects such as moths and katydids, which also frequently communicate in ultrahigh frequencies. Because tarsiers' perky ears are so sensitive, they may be able to intercept this chatter at night—then zoom in for the kill.

But they may just as much want to avoid being eavesdropped on. Their nails-on-a-chalkboard trills are too high-pitched for predators such as birds to notice, letting mothers and infants talk without drawing the attention of the entire forest. Ramsier thinks that hidden communication may be more common than many researchers suspect. Scientists, she says, rarely think to listen for ultrasonic noise. "I want everyone to go out with their bat detectors."

"It's a neat paper," says Mark Coleman, who studies primate hearing at Midwestern University in Glendale, Arizona. But he's not convinced that ultrasonic communication is so underappreciated in primates. Based on the shapes of their inner ears, early mammals likely vocalized a lot using ultrasonic frequencies, the better to hide from hungry dinosaurs, he suggests. Tarsiers, unlike most other primates, may be one of the few species to have retained this ability. "They're kind of a holdover from this really ancestral mammal ... where high-frequency communication was the norm."

More Than 4 Million Americans Have New Knee

More than 4 million Americans now live with an artificial knee, and increasing numbers of younger patients are undergoing knee replacement surgery, new research reveals.

Researchers at Brigham and Women's Hospital in Boston estimate that more than half of adults who are diagnosed with knee osteoarthritis will receive a total knee replacement in their lifetime.
Senior author Elena Losina, co-director of the hospital's Orthopaedic and Arthritis Center for Outcomes Research, said the country's aging population and high rates of obesity are only partly responsible for the rise in total knee replacements.

"We think that as more and more people began participating in active sports, they sustained injuries earlier in life, and therefore developed knee osteoarthritis earlier," Losina said. "And these active people are probably more willing to undergo surgery that will enable them to continue to be active."
Also, with improved success rates over the past 20 years, "surgeons are more comfortable offering it, and patients are more comfortable having it," Losina added.

A shorter postoperative hospital stay has also made the procedure more acceptable, she said. "Ten or 15 years ago, patients stayed in the hospital for a week," Losina said. "Now, they're usually discharged on the third day after surgery."

The number of new-knee procedures doubled over the last decade, reached more than 620,000 in 2009, and the researchers said younger patients -- those 45 to 64 -- accounted for a disproportionate amount of that growth. Their relatively young ages means many are at risk of revision surgery as well as potential long-term complications of surgery, the authors warned.

The researchers estimate that more than 4.2 million Americans currently have an intact total knee replacement, which represents 4.4 percent of the total population aged 50 and over. Prevalence is slightly higher in women versus men.

They further estimate that nearly 53 percent of men and 52 percent of women diagnosed with symptomatic knee [osteoarthritis] will receive a total knee replacement in their lifetimes. The risk of subsequent revision is nearly 15 percent for men and roughly 18 percent for women, the authors wrote.

In osteoarthritis of the knee, the cartilage wears down, causing changes in the adjacent bone, resulting in pain, swelling and stiffness.

The study is scheduled for presentation Friday at an American Academy of Orthopaedic Surgeons' meeting in San Francisco. The researchers' data included information from the U.S. Census, two national studies on people with knee arthritis, and a computer model on the history and management of knee arthritis.

One leading orthopedic surgeon, Dr. William J. Robb III, chairman of the department of orthopaedic surgery at NorthShore University Health System in Evanston, Ill., said the findings were useful in that they provided more details about the number of patients now living with artificial knees. But he questioned the estimate of patients who might require revision surgery.

"The study used historical failure and complication rates to predict future numbers of failures that might require revision surgery," Robb said. "The methodology used likely projects the 'worst-case scenario' for total numbers of failures, as implant materials have been improved and those improvements may decrease the overall revision rate."

The study was funded by the U.S. National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Data and conclusions presented at medical meetings should be viewed as preliminary until published in a peer-reviewed medical journal.

SOURCES:
 Elena Losina, Ph.D., co-director, Orthopaedic and Arthritis Center for Outcomes Research, Brigham and Women's Hospital, Boston; William J. Robb III, M.D., chairman, Department of Orthopaedic Surgery, NorthShore University Health System, Evanston, Ill; Feb. 10, 2012, presentation, American Academy of Orthopaedic Surgeons, annual meeting, San Francisco

Patient information: Type 1 diabetes mellitus and diet

TYPE 1 DIABETES OVERVIEW

Diet and physical activity are critically important in the management of the ABCs (A1C, Blood pressure and Cholesterol) of type 1 diabetes. To effectively manage A1C (hemoglobin A1c) and achieve stable blood sugar control, it is important to understand to understand how to balance food intake, physical activity, and insulin.
Making healthy food choices every day has both immediate and long-term effects. With education, practice, and assistance from a dietitian and/or a diabetes educator, it is possible to eat well and control diabetes.
This topic discusses how to manage diet in people with type 1 diabetes. The role of diet and activity in managing blood pressure and cholesterol is reviewed separately. (See "Patient information: High blood pressure, diet, and weight" and "Patient information: High cholesterol and lipids (hyperlipidemia)".)

WHY IS DIET IMPORTANT?

Many factors affect how well diabetes is controlled. Many of these factors are controlled by the patient, including how much and what is eaten, how frequently the blood sugar is monitored, physical activity levels, and accuracy and consistency of medication dosing. Even small changes can affect blood sugar control.
Eating a consistent amount of food every day and taking medications as directed can greatly improve blood sugar control and decrease the risk of diabetes-related complications, such as coronary artery disease, kidney disease, and nerve damage. In addition, these measures impact weight control. A dietitian can help to create a food plan that is tailored to your medical needs, lifestyle, and personal preferences.

TYPE 1 DIABETES AND MEAL TIMING

Consistently eating at the same times every day is important for some people, especially those who take long-acting insulin (eg, NPH). If a meal is skipped or delayed, you are at risk for developing low blood glucose.
People who use intensive insulin therapy (those on an insulin pump or multiple daily insulin injections) have more flexibility around meal timing. With these regimens, skipping or delaying a meal does not usually increase the risk of low blood sugar.

High fat meals — Foods or meals that are high in fat (eg, pizza) may be eaten occasionally, although blood glucose levels should be monitored more closely. High-fat meals are broken down more slowly than low-fat meals. When using rapid acting insulin (eg, Humalog, Novolog) before a meal, the blood sugar level may become low shortly after eating and then rise hours later.

People who use an insulin pump can use an extended insulin delivery regimen to better manage blood sugar levels after eating a high-fat meal. People who give insulin injections do not generally adjust their treatment based upon the fat content of their meal.

TYPE 1 DIABETES AND CARBOHYDRATE CONSISTENCY

Carbohydrates are the main energy source in the diet, and include starches, vegetables, fruits, dairy products and sugars. Most meats and fats do not contain any carbohydrates.
Carbohydrates have a direct impact on the blood sugar level whereas proteins and fat have little to no impact. Eating a consistent amount of carbohydrates at each meal can help to control blood sugar levels, especially if you take long-acting insulin (eg, NPH).
There are several ways to calculate carbohydrate content of a meal, including carbohydrate counting and exchange planning.

Carbohydrate counting — A dietitian usually helps to determine the number of carbohydrates needed at each meal and snack, based upon your usual eating habits, insulin regimen, body weight, nutritional goals, and activity level. In most people, between 45 and 65 percent of the day's total calories should come from carbohydrates.

The way carbohydrates are divided up for each meal or snack is based upon personal preferences, meal timing and spacing, and type of insulin regimen (table 1).
The number of carbohydrates in a food can be determined by reading the nutrition label, consulting a reference book or website, or carrying a database on a personal digital assistant (PDA). Restaurants usually have this information available upon request. (See 'Where to get more information' below.)
It is important to note the serving size and grams of fiber when calculating carbohydrates. Eating more than one serving will increase the number of calories consumed and the dose of insulin needed to cover the meal. For example, some pre-packaged snacks contain 2 or more servings. To calculate the carbohydrate content of the entire package, multiply the number of servings by the number of carbohydrates.
When a serving of food has more than 5 grams of fiber, the grams of fiber should be subtracted from the grams of carbohydrates to calculate the insulin dose (figure 1) [1].

Intensive insulin therapy — People who use an insulin pump or take multiple injections of rapid-acting insulin per day can adjust their pre-meal insulin dose based upon the number of carbohydrates they plan to eat and their pre-meal blood sugar. This requires the person to perform basic arithmetic.

The pre-meal insulin dose is calculated by dividing the number of carbohydrates to be consumed by the number of carbohydrates covered by one unit of insulin (insulin-to-carbohydrate ratio). This dose is then adjusted based upon the pre-meal blood sugar reading (see correction factor below). Some insulin pumps can perform these calculations.

• Insulin-to-carbohydrate ratio — An insulin-to-carbohydrate ratio is determined by a dietitian or diabetes educator. This allows you to calculate the dose of rapid-acting insulin needed to cover a meal or snack.
  
  For example, if the insulin-to-carbohydrate ratio is 1 to 10, then you would give 1 unit of insulin for every 10 grams of carbohydrate consumed. If you ate a meal with 70 grams of carbohydrates, the dose of rapid-acting insulin would be 7 units. Most insulin pumps are able to give tenths of a unit, so that 78 grams of carbohydrate would require 7.8 units of insulin.
• Correction factor — The pre-meal insulin dose can also be adjusted based upon the pre-meal blood sugar level; this is called a correction factor. The correction factor can be determined by a dietitian or diabetes educator.
  
  For example, let's assume that the correction factor is 30. If the pre-meal blood sugar was 240 mg/dL and the goal BG was 120 mg/dL, take 240 minus 120 = 120. Then divide 120 by 30 = 4 extra units of insulin to correct the high blood sugar level.
  
  For patients whose blood sugar is measured in mmol/L, a different formula is used. Let's assume a correction factor of 2. If the pre-meal blood sugar was 14 mmol/L and the goal blood sugar was 6 mmol/L, take 14 minus 6 = 8. Then divide 8 by 2 = 4 extra units of insulin to correct the high blood sugar.

Exchange planning — With exchange planning, all foods are categorized as either a carbohydrate, meat or meat substitute, or fat. In this system, one serving of a carbohydrate (eg, 1 small apple) can be exchanged for any other carbohydrate (eg, 1/3 cup cooked pasta) because both servings contain about 15 grams of carbohydrate.

The exchange lists also identify foods that are good sources of fiber, and foods that have a high sodium content. A dietitian can determine how many servings of each group should be eaten at each meal and snack (table 2).

WHAT SHOULD I EAT?

While protein and fat do not affect blood glucose levels significantly, they do contribute to the number of calories consumed. Eating a consistent number of calories every day can help to maintain body weight. An individual's recommended calorie intake is discussed below. (See 'Recommended calorie intake' below.)

General recommendations — The American Diabetes Association recommends the following to help manage the ABCs (A1C, blood pressure and cholesterol) and promote good health:

• Less than 25 to 35 percent of calories per day should be from fat, and less than 7 percent of calories per day should be from saturated fat; there should be minimal trans fat. Saturated and trans fats are found in solid fats like butter, margarine, and shortening. People with diabetes are at increased risk for heart disease and stroke, and eating a diet low in saturated and trans fats and cholesterol diet can help to manage cholesterol levels and decrease these risks.
• Total cholesterol intake should be less than 200 mg per day. The main sources of cholesterol in the diet are foods such as organ meats, egg yolks, and whole milk.
• Between 15 and 20 percent of calories should be from protein, except in people with certain kidney problems (chronic kidney disease or CKD). People with CKD are sometimes advised to eat a low-protein diet. (See "Patient information: Chronic kidney disease".)
• A diet that is high in fiber (25 to 30 grams per day) may help to control blood sugar levels and AIC. (See "Patient information: High-fiber diet".)
• A diet that is low in sodium (less than 2300 mg per day) and that is high in fruits, vegetables, and low fat dairy products, is recommended and can help manage blood pressure. For people with diabetes and heart failure, a low sodium diet may reduce symptoms. (See "Patient information: Low sodium diet".)
• Artificial sweeteners do not affect blood sugar levels and may be consumed in moderation. The US Food and Drug Administration has approved five artificial sweeteners: aspartame (Equal, NutraSweet), saccharin (Sweet'N Low, Sweet Twin), acesulfame-K (Sunnet, Sweet One), neotame, and sucralose (Splenda).
  
  Sugar alcohols (sorbitol, xylitol, lactitol, mannitol, and maltitol) are often used to sweeten sugar-free candies and gum, and increase blood sugar levels slightly. When calculating the carbohydrate content of foods, one half of the sugar alcohol content should be counted in the total carbohydrate content of the food. Eating too much sugar alcohol at one time can cause cramping, gas, and diarrhea.
• Previously, people with diabetes were told to avoid all foods with added sugar. This is no longer necessary, although sugar should be eaten in moderation. If you take insulin, calculate your dose based upon the number of carbohydrates, which already includes the sugar content, as described above. (See 'Carbohydrate counting' above.)
• Products that are "sugar-free" or "fat-free" do not necessarily have a reduced number of calories or carbohydrates. Read the nutrition label carefully and compare it to other similar products that are not sugar- or fat-free to determine which has the best balance of serving size and number of calories carbohydrates, fat, and fiber.
  
  Some sugar-free foods, such as diet soda, sugar-free gelatin, and sugar-free gum, do not have a significant number of calories or carbohydrates, and are considered "free foods". Any food that has less than 20 calories and 5 grams of carbohydrate is considered a free food, meaning that there are not enough calories or carbohydrates to affect your weight or require additional insulin.

Recommended calorie intake — The number of calories needed to maintain weight depends upon your age, sex, height, weight, and activity level. In general:

• Men, active women — 15 calories/pound
• Most women, sedentary men, and adults over 55 years — 13 cal/lb
• Sedentary women, obese adults — 10 cal/lb
• Pregnant, lactating women — 15 to 17 cal/lb

To lose 1 to 2 pounds per week (a safe rate of weight loss), subtract 500 to 1000 calories from the total number of calories needed to maintain weight.
As an example, an overweight man who weighs 250 lbs would need to eat 2500 calories per day to maintain his weight. To lose weight, he should eat 1500 to 2000 calories per day. As weight is lost, his recommended calorie intake should be recalculated.

TYPE 1 DIABETES, DIET, AND WEIGHT

Your weight is a direct reflection of how much you eaten and how active you are. Eating a consistent number of calories every day can help to control blood sugar levels and maintain body weight.

Avoiding weight gain — Weight gain is a potential side effect of intensive insulin therapy in type 1 diabetes. To avoid weight gain, the following tips are recommended.

• Measure your weight on a regular basis (eg, once weekly). Weight gains of more than 2 to 3 pounds indicate a need to decrease what you eat or increase your activity. Do not wait until weight increases by 10 or more pounds to take action.
• As blood sugar control improves, it may be necessary to decrease your calorie intake by 250 to 300 calories to avoid weight gain.
• If blood sugar levels are frequently low at a particular time of day, talk to a healthcare provider about decreasing the insulin dose rather than adding a snack.

Exercise — Exercising regularly can help to lose weight and keep it off. The recommended amount of exercise is 30 minutes per day most days of the week. (See "Patient information: Exercise".)

People who take insulin should check their blood sugar level before and after exercising. If exercise is vigorous and prolonged (more than thirty minutes), check your blood sugar every fifteen minutes (if the exercise regimen is new and will be used again). Frequent monitoring can help to get a sense of what effect exercise has on your blood sugar level.
If your blood sugar becomes low during exercise, eat a snack according to the guidelines below. (See "Patient information: Hypoglycemia (low blood sugar) in diabetes mellitus".)

• If the blood glucose is 51 to 70 mg/dL (2.8 to 3.9 mmol/L), eat 10 to 15 grams of fast-acting carbohydrate (eg, 1/2 cup fruit juice, 6 to 8 hard candies, 3 to 4 glucose tablets).
• If the level is less than 50 mg/dL (2.7 mmol/L), eat 20 to 30 grams of fast-acting carbohydrates.

Retest after 15 minutes and repeat treatment if needed. If the next meal is more than an hour away, eat an additional 15 grams of carbohydrate and 1 ounce of protein (for example, crackers with cheese or one-half of a sandwich with peanut butter). Try not to eat too much because this can raise blood sugar levels above the target level and lead to weight gain over the long term.

Adjusting insulin dose for exercise — It may be possible to reduce the insulin dose before exercising to avoid developing low blood glucose. A physician, diabetes educator, or exercise physiologist can help to determine the best way to adjust your insulin dose before, during, and after exercising. People who take oral diabetes medications usually do not need to adjust the dose of these medications for exercise.

TYPE 1 DIABETES AND ALCOHOL

Drinking a moderate amount of alcohol (up to 1 serving per day for women, up to 2 servings per day for men) with food does not affect blood sugar levels significantly. Alcohol may cause a slight rise in blood sugar, followed hours later by a decrease in the blood glucose level. As a result, it is important to monitor blood sugar response to alcohol to determine if any changes in insulin doses are needed.
Mixers, such as fruit juice or regular cola, can increase blood sugar levels and increase the number of calories consumed in a day. If mixers are consumed, a dose of insulin may be needed.

TYPE 1 DIABETES AND EATING DISORDERS

Eating disorders are relatively common in people with diabetes, especially in female adolescents and young adults with type 1 diabetes. This may be due, in part, to the difficulty of balancing food intake, exercise, and blood sugar levels, which sometimes leads to weight gain, especially in people who use intensive insulin therapy or an insulin pump.
People with eating disorders and diabetes often use unhealthy strategies to control their weight, including:

• Giving less insulin than required (or no insulin)
• Severely restricting the amount of food eaten
• Eating a large amount of food at one time (binge eating). After binging, some people vomit (purge), use laxatives inappropriately, or exercise excessively.

Eating disorders can cause serious complications in anyone, although the consequences for people with diabetes can be especially severe. The kidneys and retinas (in the eyes) are at high risk of becoming damaged as a result of eating disorders, especially if blood sugar levels are chronically high due to underdosing of insulin. Missing or underdosing insulin, even occasionally, is harmful.
If you have concerns about your body weight, size, or shape, you should speak honestly with your healthcare provider. The provider can help to make a plan that includes a reasonable diet, exercise, and if needed, counseling regarding body image.