Scientists have identified a single-gene mutation that enables people to function effectively with far less sleep than most, a discovery that could lead to improved understanding of sleep cycles and open up new paths toward the treatment of insomnia and other sleep disorders.

Ying-Hui Fu and colleagues at UCSF made the find while conducting routine DNA screening on blood samples from people that had participated in several sleep studies.

The scientists had been searching for gene variations that affect circadian rhythms and other aspects of the sleep cycle. When they identified 2 specimens having unusual mutations of the so-called DEC2 gene, they traced them back and found a mother and daughter who routinely functioned on 6 hours of sleep per night. The average requirement is 8 to 8.5 hours per night.

The scientists then bred mice to have the same mutation, and found they required less sleep and recovered more easily from experimental sleep deprivation than regular mice.

The study “opens up a window to understanding the genetic basis of individual differences in sleep duration. You have a piece of the puzzle and you can begin trace back,” Charles Czeisler told the New York Times. He’s chief of sleep medicine at Brigham and Women’s Hospital.

The 2 women turn in around 10 or 10:30 each night and wake up ready to rock and roll at 4 or 4:30 in the morning, according to Fu.

Many people sleep for six or fewer hours per night, but have to use stimulants and alarm clocks to pull off the feat. “That’s a very different thing,” Fu told the Times. “Our body needs 8 to 8.5 hours.” (more…)

For legions parents that have endured far too many sleepless nights trying to console colicky babies, relief might be on the way.

Scientists think they’ve identified a bacterium that causes the nerve-racking condition, in which otherwise healthy babies scream for hours.

Colic affects nearly 15% of all infants in the US.

Pediatrics professor J. Marc Rhoads and colleagues at the University of Texas are proposing that Klebsiella is the culprit. The gram-negative bacterium resides in the gastrointestinal tracts of humans of every age, but in colicky babies only, the bug seems to trigger an inflammatory reaction in the intestines.

In non-colicky babies, Klebsiella causes no such disturbance.

Previous theories held that babies receiving cow’s milk were more likely to suffer from colic, but research on the matter has failed to support that claim. The colicky babies in Rhoads’ study for example, included some who were fed breast milk and some who received formula.

Rhoads speculated that colic might actually be a precursor to other gastrointestinal maladies ranging from  irritable bowel syndrome to Celiac disease. “Inflammation in the gut of colicky infants closely compared to levels in patients with inflammatory bowel disease,” he told BurrillReport.

The write-up appears in Pediatrics.

Typicially, pediatricians prescribe hypoallergenic formulas for the treatment of colic, but as harried parents can attest, the approach is often ineffective.

Rhoads believes his teams’ discovery might eventually save lives.

“Colic can be a dangerous situation for a baby. The parent’s frustration over the crying can lead to maternal frustration, post-partum depression, and even thoughts of harming the baby,” he told Burrill.

“More than half of infanticides fall into the age category of colic. We may be able to prevent deaths if we can find a treatment.”

Two over-the-counter medicines used to treat itchy eyes and runny noses might be effective treatments for obesity and Type 2 diabetes, according to a pair of papers in Nature Medicine.

The allergy drugs Zaditor and cromolyn are immune system modulators, and scientists have come to believe there’s a link between immune system activity and these common conditions. 
 
In the first study, Guo-Ping Shi, a biochemist from Brigham and Women’s Hospital noticed a plethora of mast cells—which normally facilitate wound healing by increasing blood flow to the site and are also implicated in the etiology of asthma and allergic reactions—in the fat tissue of obese and diabetic humans and mice. 

Shi  showed that Zaditor or cromolyn could quell mast cell activity in this tissue and that was associated with  reduced body weight and more easily controlled diabetes in mice. 
 
Following this, Shi showed that genetically engineered mice that could not produce mast cells did not become obese or develop diabetes, even while being fed a high calorie diet which produced these conditions in normal mice.
 
“The best thing about these (2 allergy drugs) is that (they’re) safe for people,” Shi explained to BurrillReport. “The remaining question now is: Will this also work for people?”
 
She intends to test the drugs on obese and diabetic primates as a next step.

In the second study, Joslin endocrinologist Steven Schoelson and colleagues showed that fat tissue in obese and diabetic subjects contained fewer regulatory T cells than that in normal-weight humans and mice.  
 
The paucity of these cells created an overabundance of macrophages and other inflammation-generating cells in the fat tissue of obese and diabetic subjects.
 
“It’s possible that the inflammation caused by macrophages results in insulin resistance,” Shoelson told Burrill.

“And it’s likely that (regulatory T cells) are keeping the macrophages in check in normal fat tissue, thus preventing inflammation.”

Who says Aromatherapy is simply a New Age fad?

Japanese scientists have recently shown that inhaling fragrant scents like lemon, mango, and lavender alters gene activity and blood chemistry, with the net effects being reduced stress levels, resistance to inflammation and depression, and improved sleep… in lab rats.

The beneficial effects seem to be caused by linalool, a chemical previously thought to contribute nothing more than a pleasing odor associated with foods and flowers such as basil, grapes, oranges, tomatoes and tea.

In their experiments, Akio Nakamura and colleagues from the Graduate School of Agricultural and Life Science at the University of Tokyo showed linalool does far more than that.

The scientists divided rats into 3 groups. The control group was exposed to neither stress nor odor. The second was exposed to stress only, in the form of mildly restraining their free movements for a period of 2 hours. The third group was exposed to both stress and inhaled linalool.

In all 3 groups, the researchers assessed stress hormone levels, blood cell counts and gene expression. 
 
The simply stressed-out rats were found to have elevated levels of circulating white blood cells as expected, but those exposed to both stress and linalool had normal WBC counts.

In other words, the linalool attenuated stress-related bumps in white blood cell counts.

Similarly, stress-related elevations in heart rate were blunted by linalool, and the stuff was also shown to down-regulate the activity of 109 genes that normally get turned on during stressful situations, and up-regulate the expression of 6 genes that are normally turned off during such situations.

Investigators attributed much of the physiological impact to sedative effects of the compound. The write-up appears in the Journal of Agricultural and Food Chemistry.

The National Cancer Institute has funded cutting-edge research for years, but now it’s engaged in some innovation on the financial side of things, and the initiative might just help the venerable institution improve the ROI on its own investments.

The NCI’s idea is to set aside funds that help emerging companies forge the “valley of death,” a term describing the period after their SBIR funding is exhausted and before they are ready to raise funds from an increasingly penurious VC community. 

According to BurrillReport, then acting NIH Director Elias Zerhouni hatched the idea upon realizing that $650 million invested by NIH in the Small Business Innovative Research program was not yielding adequate returns in the form of newly commercialized drugs and devices.

Zerhouni charged the NCI’s Michael Weingarten and Andy Kurtz to remedy matters, and they came up with the concept of the Bridge Awards.

“A lot of projects die on the vine when they exhaust the usual funding through the SBIR program. The idea with the Bridge Awards was to provide additional funding for the most promising projects,” Kurtz explained to Burrill.

The NCI recently issued its first round of Bridge Award grants and is now reviewing a second round. The 3-year grants top-out at $3 million.

Bridge Award applicants must match NCI funds on a dollar-for-dollar basis via external funding mechanisms. The Award provides non-dilutive capital and a measure of independence for the  companies while helping the NCI to validate the commercial potential of the company’s product.

“It’s money that buys you some runway or buys you time to a next milestone where you can get traditional venture capital,” Ernst & Young’s Glen Giovannetti explained.

“With NIH, there’s a process by which you have to qualify, so there is a scientific review and validation that comes from that.”

Several conditions associated with aging, such as atherosclerotic blockages of the arteries and cataracts can be treated nowadays, but for osteoarthritis, a condition that affects millions in this country alone, little can be done save the administration of anti-inflammatory agents and pain relievers.

Osteoarthritis of the knees can be particularly unfortunate since afflicted individuals typically cut down their physical activity in response, and this can exacerbate or cause other health conditions like diabetes. 

A cure does not appear imminent, but a new technique developed by Lior Shamir and colleagues at the NIH might just be able to predict who will get the condition 20 years prior to symptom onset.

This would be good since people found to be at risk could be encouraged to lose weight, exercise properly, and alter their diet to ward off the onset of the painful condition.

Shamir’s group digitized 200 x-rays that were taken in the 1980s for a project designed to document human aging. All radiographs had been read as normal at the time.

Since the images were obtained, many of these people developed osteoarthritis of the knees.

The researchers sorted the original x-rays into 2 groups: one group included “normal” pictures from the people that eventually developed osteoarthritis while the other had pictures from people that did not.

The researchers then looked for subtle structural alterations of the bone and cartilage in both groups of x-rays.

From the inter-group differences they detected, they built a computer algorithm designed to predict which individuals would eventually develop osteoarthritis and which would not.

Their algorithm proved to be accurate 72% of the time, an astonishing finding considering that the x-rays had originally been read as normal and that they were obtained 20 years before symptom onset.

The write-up is in Osteoarthritis and Cartilage.

Asthma is common in first world nations, unheard of in the developing world and rising quickly in countries making the transition.

Many theories have been posited to explain this association. They range from the idea that clean living somehow revs-up the immune system to a belief that swimming pool chemicals bring on the allergy-mediated condition.

The common denominator is that environmentally mediated phenomena associated with economic development are directly triggering asthma.

Shadmehr Demehri and colleagues at Washington University in St. Louis have postulated an indirect link, in which environmental factors trigger eczema, a benign though annoying skin condition, and the distressed skin cells create chemical signals that in turn trigger asthma. 

Eczema is also linked to economic development. Nearly 17% of US children have it, and nearly 70% of children with eczema develop asthma, even though the prevalence of the letter condition in the general population is only 4-8%.

Demehri’s team believes the culprit is thymic stromal lymphopoietin (TSLP), an immune-stimulating molecule released by skin cells when they are damaged, as by eczema. TSLP, they theorize, causes lung tissue to over-react to allergens, which leads to asthma.

The team wrote-up the results of 3 experiments in the Public Library of Science Biology that provide support for its hypothesis.

First, the scientists showed that mice genetically engineered to develop eczema were prone to develop asthma. Then they deleted the gene coding for the TSLP receptor in the bronchial tissue of such mice and voila, the new editions did not develop asthma.

In the third step, the scientists created mice that over-produced TSLP in the absence of skin problems. These mice wheezed up the wazoo.

Case closed, at least in mice. Eczema is easily treated, by the way, with low-dose topical steroids.

Cancer research trials published in peer-reviewed journals tend to include a disproportionately small number of women, according to a study published in Cancer.

To reach this conclusion, Reshma Jagsi and her colleagues at the University of Michigan reviewed 661 prospective studies involving more than a million subjects who had non-gender specific cancers like those of the colon, head and neck, lung, brain and lymphomas.

“In the vast majority of studies we analyzed, fewer women were enrolled than we would expect given the proportion of women diagnosed with the type of cancer being studied,” Jagsi told BurrillReport.

Jagsi added, “we’re seeing it in all cancer types. We know there are biological differences between the sexes, as well as social and cultural differences. Studies need to assess whether there are differences in responses to treatment between women and men.”

The practice flies in the face of the NIH’s Revitalization Act of 1993, which highlighted the need to include women in research studies in numbers sufficient to support gender-specific subgroup analyses.

Government-funded studies did include slightly higher numbers of female participants: 41% of subjects in such trials were women, whereas only 37% of the subjects in non-government-funded studies were women.

The authors suggested several reasons for the discrepancy. For example, scientists tend to avoid including “vulnerable populations,” such as women of childbearing age in their studies. “By protecting them from research, we’re excluding them,” the scientists concluded.

Other barriers are thought to include a lack of information, fear, and a belief that the studies interfere with individual responsibilities including child care.

The authors suggest that among other things, investigators should reimburse participants for transportation and child care expenses incurred during the study.

Ever since a 2007 trial of Avandia raised concern that newer generation diabetes-fighters raised cardiovascular risk, sales of the drugs have crashed and investigators have scurried to provide follow-up data one way or the other.

Now, Bristol Meyers Squibb scientists have raised hope that a diabetes drug in the pipeline may actually cut cardiovascular risk.

The drug is saxagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor.

At the ADA meetings last month, Robert Wolf and colleagues reported the results of a meta-analysis, in which they pooled results from 8 phase II and III trials of the drug.

They found major adverse cardiovascular events to be 55% less common in saxagliptin-treated patients than in those receiving either placebo or metformin.

If confirmed with prospective trials, this cardioprotective effect “would be a very important advance,” Wolf told MedPageToday.

The meta-analysis combined 4,607 adverse events reported during 3,758 patient-years of study in 8 randomized, double-blind trials of saxagliptin in type 2 diabetes.

The incidence of major adverse cardiovascular events, which include cardiovascular death, nonfatal MI, and nonfatal stroke was 0.7% in saxagliptin-treated patients and 1.4% in the other groups.

Saxagliptin was found to cut CV risk in high-risk subsets as well. For example, among those with a prior history of cardiovascular disease, the incidence of major adverse CV events was 9.2% in saxagliptin-treated patients versus 46.3% in other groups.

Equally impressive reductions were seen in populations with at least one CV risk factor beyond diabetes, at least 2 risk factors in addition to diabetes, in men, and in those at least 65 years old.

The drug’s codevelopers, BMS and AZ, have submitted an NDA to the FDA, which is expected to rule on the matter later this month.

In December, 1997, goats, cattle and sheep began dropping dead in north-eastern Kenya. A month later people began doing the same. The cause was Rift Valley fever. Nearly 100,000 animals died and as many humans were infected. Hundreds of people died.

Exactly ten years later, livestock once again began dying off in the same area, but the outbreak was largely avoided in humans because NASA scientists had tipped off the Kenyans before things got nasty.

Acting on the news, Kenyan officials distributed mosquito nets and told folks to stop eating their livestock. The 2007 outbreak killed 300 people, but the number would have been twice that or more without the head’s up.

The warning resulted from the research of Kenneth Linthicum, of the US Department of Agriculture, who used data derived from satellites to predict the outbreak. 

Linthicum and his colleagues noticed in retrospect that the first outbreak was preceded by a rise of one degree Fahrenheit in the surface temperatures of the Indian Ocean near the east coast of Africa.

That had triggered monsoon rains and cloudy, warm weather over the Horn of Africa, which caused explosive growth in the mosquito population. Linthicum’s team saw the same thing happening in September, 2007.

Heretofore, efforts to predict epidemics relied on slow, expensive fieldwork. Satellite data is cheaper to obtain. It includes information about precipitation, temperature, vegetation cover and chlorophyll production.

Confirming the value of satellite-derived information, Jacques-André Ndione of Dakar’s Centre de Suivi Ecologique cites a satellite study showing that malaria spreads more quickly in suburbs than in cities.

In that study, satellite images revealed that suburbs have more ponds and puddles, and that their longevity, salinity and mud content tended to favor mosquito happy times.

Incidentally, the EDEN project, a public-health cooperative involving European and African countries, has used satellite findings to conclude that malaria, dengue fever and Rift Valley fever will soon enter Europe.

Indeed, chikungunya, a mosquito-borne viral disease previously found only in tropical Africa and Asia, has recently shown up in Italy and Albania. A sign of things to come, maybe?

The millions of folks with no cardiac history who have been diligently popping baby aspirin to prevent future cardiovascular events might as well flush ‘em down the toilet, according to the results of a meta-analysis performed by Oxford University scientists.

In such people, aspirin did reduce the combined risk of heart attack, stroke, and vascular death from 0.57% per year to 0.51%, a significant finding, but it also bumped the risk of gastrointestinal and all extracranial bleeding from 0.07% per year to 0.10%, negating any overall benefit.

Colin Baigent and colleagues oversaw the trial, known as Antithrombotic Trialists’ Collaboration, and published their findings in Lancet.

Current American Heart Association and US Preventive Services Task Force guidelines recommend baby aspirin for primary cardioprevention in those deemed to have a moderately high risk for developing heart disease.

The “current guidelines may need to be reviewed,” Biagent stated matter-of-factly to MedPageToday. For primary prevention, “the main strategies ought to be stopping smoking — if people smoke – and then if further measures are needed, lowering blood pressure, lowering cholesterol.” Baigent added.
 
The scientists had pooled data from 6 randomized, controlled trials of aspirin for the primary prevention of cardiovascular disease. Collectively, the trials had enrolled 95,000 individuals.

Subset analyses involving gender, older age, and a history of either diabetes or high blood pressure revealed nothing to chirp about. In these groups as well, any benefits in cardiovascular risk were offset by increased bleeding.

By the way, Biagent’s group also took a quick peek at secondary prevention, and confirmed that the benefits of aspirin outweigh the risks in individuals with a history of cardiac disease.

Two months ago, scientists at the University of Pennsylvania announced they developed a remarkably accurate screening test for Alzheimer’s disease.

Unfortunately, the test necessitates a spinal tap which is only slightly less odious than say, colonoscopy.

That’s why many were elated to learn that scientists at UCSF just developed a noninvasive, 15-point assessment tool that does pretty much the same thing, albeit sacrificing some diagnostic accuracy in the process.

Sexagenarians that score eight or higher on the scale are at high risk of developing dementia within the next 6 years, according to lead author Deborah Barnes.

Many items on the test are known risk factors for the condition, including old age, low scores on thinking skill tests, and having a gene linked to the disease.
 
Others are less obvious, including being underweight, completely abstaining from alcohol, a history of coronary bypass surgery, and difficulty with simple physical tasks like buttoning a shirt.
 
“This new risk index could be very important both for research and for people at risk of developing dementia and their families,” Barnes told BurrillReport. “It could be used to identify people at high risk for dementia for studies on new drugs or prevention methods.”

To develop the index, the scientists followed 3,375 elderly people for 6 years. Subjects had no evidence of dementia at study onset, but 480 had developed the condition by the end of the observation period.

The scientists then determined using logistic regression which combination of factors best predicted dementia onset.
 
Nearly 56% of those with high scores on the test developed dementia, compared with 23% of subjects having moderate scores and 4% among subjects with low scores. Overall, 88% of subjects ended up being correctly classified by the test.
 
The study is in Neurology.

Soon after treatment onset, high-dose Lipitor cuts inflammation in carotid plaques and reduces the incidence potentially dangerous cerebral microemboli, say scientists from Cambridge University.

Their study also provides early validation of a new method for detecting inflammation in such plaques. This could prove to be a boon for those who study atherosclerosis of the carotid arteries, a risk factor for stroke.

Jonathan Gillard and colleagues test-drove ultrasmall superparamagnetic iron oxide particles as the contrast agent in their MRI-based study.

The particles are ingested by macrophages, a major constituent of inflamed plaques which often cause strokes.

Heretofore, the only noninvasive means to detect vessel inflammation had been fluorodeoxyglucose positron emission tomography, but radiation exposure associated with repeated PET scanning limits its use in studies requiring repeat scans to assess disease progress.

In the study, Gillard’s team randomized 47 high-risk plaque-afflicted patients to receive either 10- or 80-mg of Lipitor once per day for 12 weeks.

MRIs performed at 6 weeks revealed a marked reduction in macrophage activity, but only in the group randomized to receive 80 mg of Lipitor. MRIs at 12 weeks showed continued improvement, but again only in the high-dose group.

In these patients, cerebral microemboli counts, as measured by transcranial Doppler, fell 91% compared with baseline.

The write-up appears in the Journal of the American College of Cardiology.

“Our study may support the hypothesis that dampening of plaque inflammation rather than morphological regression (may be responsible for the) the early beneficial effects of statins seen in clinical practice,” wrote the scientists.

Still, it’s too early to pop the corks, at least for the new imaging technique. The contrast agent may promote oxidation of LDL cholesterol in the plaque which might cause it to destabilize and rupture.

When it comes to the early diagnosis of autism, scientists are on a roll.

Last month, a group at Yale showed that autistic children could be differentiated from age-matched controls by their responses to visual and auditory cues in cartoons.

Now, a group at UNC has demonstrated using MRI scans that a specific part of the brain known as the amygdala was roughly 13% larger in autistic children than it was in normally developing kids, even after adjusting for age, gender and IQ.

To reach this conclusion, Joseph Piven and colleagues scanned the noggins of 50 toddlers with autism and 33 age-matched controls that were developing normally.

“We believe that children with autism have normal-sized brains at birth but at some point, in the latter part of the first year of life, (the amygdala) begins to grow in kids with autism,” Piven told CNN.

The amygdala helps people process faces and emotions, a behavior known as joint attention. Piven’s group confirmed that toddlers with big amygdalas had joint attention problems.

“We would basically try to get the child to look one way, we’d turn and point to a clock and see whether or not the child would notice it,” Piven explained. “The 2-year-olds without autism would…see where you are looking and join you but the children with autism, with large amygdalas, would not.”

Autism experts say such findings are critical in developing new ways to diagnose autism and initiate treatment earlier in the course of the disease.

Autism affects about 1 in 150 children. It is the most rapidly growing serious developmental disability in the US. The average age for diagnosis of autism is 3.

The findings appear in the Archives of General Psychiatry.

For years, physicians have debated when to start therapy for HIV-infected patients. Starting it early might delay, perhaps indefinitely, progression from a quiescent carrier state to the full blown syndrome, but it exposes patients to unpleasant, sometimes life-threatening side effects.

A study by Mari Kitahata and colleagues may have settled the argument in favor of early drug treatment.

The scientists tracked survival in 17,517 asymptomatic HIV-infected patients who started antiretroviral therapy at different points in the course of their disease, as determined by serum CD4 cell counts.

About a quarter of the subjects began therapy when their CD4 counts were in the 351- 500 range, and the remainder started therapy only after counts dropped to 350 or less.

The mortality risk was 69% higher in the latter group. These findings were confirmed in a second, separate cohort.

The write-up appears in the New England Journal of Medicine.

“This has been one of the most important questions in the last decade: what the optimal timing is for starting therapy,” Kitahata told the New York Times.

“Our study provides evidence that patients would live longer if antiretroviral treatment was begun when their CD4 count was above 350,” added Kitahata, who is director of clinical epidemiology at the Center for AIDS and STDs at the University of Washington.

National guidelines recommend beginning therapy in asymptomatic patients when CD4 counts drop below 350.

In the brains of patients with Alzheimer’s disease, A-beta proteins stick together to form plaques that are at least associated with, and may actually precipitate the clinical syndrome.

A-beta proteins are formed when enzymes known as secretases digest a larger protein known as amyloid precursor protein.

Knowing this, drug designers have tried to find something that inhibits the secretases, but so far the search has been fruitless.

Malcolm Leissring and a team at Mayo Clinic, Florida have taken a different approach. They searched for compounds that hasten the destruction A-beta proteins, and they may have hit paydirt.

In a report published in PLoS ONE, the scientists used in vitro procedures to isolate 2 chemicals that stimulate insulin-degrading enzyme or IDE, which chews up A-beta proteins faster than Owen and Jen’s white Lab Marley could dismantle a sofa.

Almost immediately after the chemicals were added to IDE, more than 99 percent of the A-beta was destroyed.
 
“This study describes the first examples of synthetic small-molecule activators of IDE, showing that activation of this enzyme is achievable,” Leissring told BurrillReport.

“If it is possible to generate drugs for human use that stimulate the activity of IDE, these agents might offer therapeutic benefit for treating and preventing Alzheimer’s disease.”
 
IDE is shaped like a clamshell that opens and shuts, like Pac-Man.

When IDE is open, A-beta fits snugly inside. The protease then closes like a Venus-fly trap and digests the A-beta.

IDE’s primary role is to digest excess insulin in the body, so small molecule activators like the ones uncovered by Leissring’s group might prove to be useful in managing diabetes one day as well.

The compounds are years away from human testing.