Older moms have a greater risk of giving birth to a child with autism, according to a study by scientists at UC Davis. 

To reach this conclusion, Janie Shelton and colleagues reviewed all births in California during the 1990s.

They found that the risk of having a child with autism jumped 18% for each 5-year increment in maternal age. A 40-year-old woman had a 50% higher risk of having an autistic child than a 25 year-old woman.
 
Previous research had identified increased paternal age as a risk factor, but this one, by far the largest of its kind, showed that father’s advanced age matters only if the mom is under 30. For older moms, the risk is predicted solely by maternal age.
 
“This study challenges a current theory in autism epidemiology that identifies the father’s age as a key factor in increasing the risk of having a child with autism,” Janie Shelton, the study’s lead author told BurrillReport. “While maternal age consistently increases the risk of autism, father’s age only contributes an increased risk when the mother is under 30 years old.”
 
“We still need to figure out what it is about older parents that puts their children at greater risk for autism and other adverse outcomes, so that we can begin to design interventions,” said Irva Hertz-Picciotto the senior author on the study.

In this regard, UC Davis scientists reported in 2008 that they found antibodies to fetal brain protein in some mothers of children with autism, but not in the mothers of normal children. Others speculate that certain environmental toxins accumulate in the body with age and may play a role as well.

The write-up appears in Autism Research.

China’s enormous investment in the field of regenerative medicine has catapulted the nation to the world’s fifth most productive contributor to the scientific literature, despite continued international condemnation of it research methods, according to a study in Regenerative Medicine.

The report was authored by Dominique McMahon and colleagues at the McLaughlin-Rotman Centre for Global Health.

It describes China’s aggressive efforts to recruit top international scientists, as well as the broadly impugned practice of administering unproven stem cell treatments to thousands of domestic and foreign patients.

Chinese researchers contributed more than 1,100 articles on the subject to peer-reviewed journals in 2008. That’s up from 37 in 2000 and more than any country in the world except the US, Germany, Japan, and the UK.

McMahon and colleagues indicate that China has recently instituted new rules governing stem cell treatments, but they need to be enforced more strictly if the nation is to repair its seedy reputation in the field.

Right now in China, more than 200 hospitals use stem cell therapy to treat patients with autism, cataracts, diabetes, Lou Gehrig’s disease, multiple sclerosis, Parkinson’s disease, stroke traumatic brain and spinal cord injury and many other conditions.
 
Yet until May 2009, China did not require such therapies to have been subjected to clinical trials designed to assess the safety and effectiveness of such therapies. 

China made the change after international experts and many Chinese researchers complained about gross violations of standard scientific research principles.

“China is an important player in regenerative medicine,” McMahon told BurrillReport. “Despite the media’s focus on stem cell tourism, the international community needs to recognize that Chinese researchers are making important contributions to the science of this field, and China should be included in international discourses on standards and regulations.”

Scientists have made some progress in their effort to develop a vaccine for cocaine addiction. The vaccine is actually a series of injections that trigger an immune response to cocaine. The newly-created antibodies prevent the drug from entering the brain and thus blunt its euphoric effects.

To assess the safety and efficacy of their coke vaccine, Thomas Kosten and colleagues at Baylor randomized 115 cocaine addicts to receive either 5 shots of the vaccine over a 12 week period or a series of similarly timed placebo injections.

They monitored cocaine intake using urinalyses.

Most subjects smoked crack cocaine. Many also used marijuana (18%), alcohol (10%), and narcotics (44%).
 
Among subjects who received all 5 shots, 38% achieved sufficient antibody levels to blunt the effects of the drug. Antibodies remained in the bloodstream for 8-10 weeks after the final stick.

In this subset, 53% of the subjects stopped using cocaine—significantly more than the 23% of subjects who did not produce enough antibodies.

The vaccine was well tolerated, with no treatment-related serious adverse events or deaths.

But the partial success was associated with some risk. Some subjects began snorting massive amounts of the drug in an effort to overcome the vaccine’s effects. Some amassed 10 times the amount in their systems than had been encountered before the trial began.

“After the vaccine, doing cocaine was a very disappointing experience for them,” Kosten told the Washington Post.  “Previous research has shown that a reduction in use is associated with a significant improvement in cocaine abusers’ social functioning and thus is therapeutically meaningful.”

Kosten plans to begin a larger vaccine trial this spring.

About 2.1 million Americans have used cocaine in the last month, studies show. 

The write-up appears in the Archives of General Psychiatry.

Plavix, the clot-busting blockbuster marketed by BMS and Sanofi, is never out of the news for long.

One story that developed legs in the last year for example, was the finding of apparent marked variability in responsiveness to the drug. This begat calls for personalized prescribing of Plavix based on genetic markers, and warnings that Nexium-The Purple Pill—impaired its effectiveness, thus creating an increased risk of vascular complications.

Now it seems, the worm has turned again on this story. Victor Serebruany and colleagues have reported that the issue of Plavix nonresponsiveness may be caused by something rather mundane: non-compliance with the drug.

To reach this conclusion, the scientists obtained blood samples from 422 heart disease patients and 209 poststroke patients that had platelet activity tests performed before and after Plavix use.

They tested these archived blood specimens for a chemically stable, carboxyl metabolite of Plavix, and then defined Plavix noncompliance to be a very low plasma concentration of this inactive metabolite.

They found that 138 patients (22%) were in fact noncompliant. Noncompliance was more frequent in stroke victims (38%) than cardiac disease patients (14%).

“Some of the patients whom we would classically describe as ‘resistant’ to clopidogrel, in that they showed low levels of platelet inhibition, in fact didn’t actually have clopidogrel on board,” Serebruany told Medscape.

“The whole variability issue with clopidogrel (Plavix) is not such a big deal,” Serebruany added. “It has been hyped by the manufacturers of the newer antiplatelet agents. If we did studies with these agents, they would show variability, too.”

“Future antiplatelet trials should recognize noncompliance as a critical confounding factor, and every attempt should be made to minimize and strictly monitor prescribed antiplatelet regimens,” the authors concluded.

How’s this for a cool high-school science project?

Brenda Tan and Matt Cost, a pair of students at Trinity High School in Manhattan, recently performed DNA analysis of food items and other objects collected in their homes and surrounding environs.

They found a hellacious mix of mislabeled and possibly tainted food items and raised a ton of questions in the process.

Among their notable discoveries:
-  A pricey chunk of so-called sheep’s milk cheese turned out to have been derived from cow’s milk,
-  Fish labeled smelt turned out to be Japanese anchovy,
-  “Venison” dog treats were actually made from beef
-  Sturgeon caviar samples contained DNA from that widely-known delicacy, the Mississippi paddlefish.

The students dubbed their project “DNAHouse.” They analyzed their collections using the Barcode of Life Database which is normally used in species identification. They secured help from DNA barcoding experts at Rockefeller University and the American Museum of Natural History for their project.

A write-up of their work appears here.

“We do not know where or why the mislabeling occurred, but most cases appeared to involve substitution of a less expensive or less desirable item, suggesting the possibility of deliberate mislabeling for economic gain,” the authors wrote. “We also think mislabeling is a serious problem because certain individuals have allergies or dietary restrictions regarding certain foods.”

Trinity has a track record for producing these kinds of stories. Last year, 2 other Trinity students created a stir by reporting that one-quarter of the fish at local markets and restaurants was mislabeled.

Of note, Tan and Cost also sampled hair from several classmates. “We were happy to report,” they wrote, “that our classmates came back as 100% human.”

Inhibiting an enzyme known as Sirt1 in a particular region of the brain helps reduce food intake, according to scientists at Brown University. The discovery could open the door to new pharmacologic options for the management of obesity.

Sirt1 is found in many tissues including the liver and pancreas.

Earlier studies had shown that Sirt 1 had a fundamental role in cell differentiation, aging and death.

In these studies, both fasting and the antioxidant compound resveratrol-which is found in red wine–activated Sirt1 in peripheral tissues. This phenomenon was associated with improved exercise capacity, improved glucose control and prolonged survival in rats.

The Brown study, conducted by Eduardo Nillni and colleagues, is the first to study Sirt1 activity in the hypothalamus, a region of the brain known to be associated with appetite. 

Nillni’s team used 2 methods to inhibit hypothalamic Sirt1 activity: pharmacological inhibition and RNA transcription blockade. Both approaches resulted in reduced food intake and weight loss.

The scientists also found that fasting increases hypothalamic expression of the Sirt1 gene, which makes it even more likely that Sirt1 plays a central role in moderating appetite and hunger in mammals.

Nillni now plans to study how obesity affects Sirt1 activity in the brain.

The write-up is in PloS One.

Drug induced increases in levels of the brain neurotransmitter norepinephrine can overcome memory problems and improve cognitive development in mice with genetically-engineered Down syndrome, according to scientists at Stanford.

Ahmad Salehi and colleagues postulate that similar interventions, if applied early enough in children with Down syndrome, might improve their cognitive development as well.
 
Their write-up appears in Science Translational Medicine.

In the article, Salehi’s group showed that drugs which enhanced norepinephrine signaling in the brains of the genetically engineered mice rapidly restored cognitive function, enabling them to handle simple challenges like building a nest.

The treated mice could make nests as well as normal mice. Untreated mice were unable to do so. The beneficial effects became apparent just hours after treatment was initiated. They waned quickly following discontinuation of the drugs.
 
Salehi’s genetically-engineered mice exhibited early degeneration of the locus ceruleus, a part of the brain that supplies norepinephrine to the hippocampus, which is involved with memory formation. The same findings have been demonstrated in humans with Down syndrome.

Several drugs that have been approved by the FDA for treatment of depression and ADHD have the same effects on brain norepinephrine levels as those used in the Stanford study. Because these drugs have proven to be safe in humans (though not infants), Salehi told BurrillReport he hoped his results would quickly lead to human trials.
 
Previous efforts to modify the course of Down syndrome with drugs have focused on acetylcholine, a separate neurotransmitter that also acts on the hippocampus.

Ever wonder why there isn’t a birth control pill for men?

Part of the reason is that the physiological mechanisms governing sperm production in men are less well understood than those governing ovulation in women.

Androgens are known to play a key role in normal sperm production and male fertility generally, but the mechanism by which androgens exert these effects had been largely unknown.

Now, a recent paper published in the FASEB Journal may have shed some light on the matter.

In the paper, Michelle Welsh and colleagues at the Centre for Reproductive Biology in Edinburgh studied androgen levels and sperm production in 2 groups of mice. The first group was normal, but the second had been engineered such that the peritubular myeloid cells in their testes lacked a particular gene that codes for an androgen hormone receptor.

In latter group, testis weight did not increase normally at puberty, and by the time they matured to adulthood they could produce only about 14% as many sperm cells as their normal counterparts. The findings were not explained by differences in testosterone, luteinizing hormone, or follicle-stimulating hormone levels.

The authors concluded that androgen action on the peritubular myeloid cells was therefore essential for normal testis function, spermatogenesis, and fertility in male mice, and seemed quite confident in their write-up that the findings would be easily reproduced in other mammals including humans.

“This study…could provide new insight for the development of new treatments for male infertility and perhaps new male contraceptives,” Welch told BurrillReport.
 
“Not only does this research pinpoint androgenic hormones and their cellular receptors as prime targets for the development of new birth control drugs, but it promises to speed the development of new agents to boost sperm production,” added Gerald Weissmann, who edits the FASEB Journal.

Drugs used to reverse anemia in cancer and kidney failure patients are largely ineffective and markedly increase the risk of blood clots, according to a study by scientists at Columbia University Medical Center.

To reach this conclusion, Dawn Hershman and colleagues studied use of the so-called erythropoiesis stimulating agents (ESAs) in more than 50,000 patients that had been diagnosed with cancer.

In these patients, ESAs did not reduce blood transfusion requirements caused by chemotherapy, but they did jack up the risk of deep venous thrombosis and pulmonary embolism.

Hershman’s study population included patients that were at least 65 years of age and had been diagnosed with cancers of the breast, colon and lung. ESAs are used frequently in such patients as adjuncts to chemotherapy.

Survival was not impacted by the ESAs.

The number of patients receiving ESAs jumped 10-fold from 1991 through 2002. By that time, nearly half of all cancer patients were receiving them.

“This analysis confirms the association between ESAs and venous thromboembolism, which was observed in previous meta-analysis,” Hershman told BurillReport. “This data is from community practice – real-life clinical settings – where you see things that wouldn’t necessarily show-up in a short-term, 12-week study.”

Leading ESAs include Amgen’s Aranesp and Epogen, and Johnson & Johnson’s Procrit. Sales of these drugs topped $10 billion in 2006 in the US alone.

The meta-analysis mentioned above prompted the FDA to issue a black-box warning regarding the potential for tumor promotion, venous thromboembolism and decreased survival with ESAs. The warning suggested that ESAs should be used only for specific tumors and only when hemoglobin levels dropped below certain levels.

The write-up appears in the Journal of the National Cancer Institute.

Microbiologists from the Food and Drug Administration may have found a new way to protect fruits and vegetables from contamination with Salmonella.

Eric Brown and colleagues at the FDA’s Center for Food Safety and Applied Nutrition have found that a particular group of naturally occurring bacteria that can wipe out the dreaded pathogen, at least in laboratory settings. 

“The beauty is that we take something alive and organic and put it back into the field, and by itself, it will kill other bacteria. We’re right on the edge of this,” Brown told scientists at conference on held last month in France.

What is more, the as-yet unclassified “good” bacteria can also destroy listeria and E. coli O15:H7, 2 other bacterial pathogens that frequently cause food-borne illnesses. The only bug that seems immune to the new hero is vibrio, the critter that contaminates oysters and other seafood.

Salmonella causes 1.4 million cases of food-borne illnesses and 500 deaths a year in the US, according to the CDC. Most people recover spontaneously from the infection, but the young, the elderly and people with weakened immune systems are susceptible to severe complications.

The bacterium used to be associated outbreaks of food-borne illnesses caused by eggs and poultry, but for unknown reasons, it has been found increasingly in association with outbreaks caused by fresh fruit and vegetables.

Last year, a salmonella outbreak was initially attributed to tomatoes, although tainted Mexican jalapeño peppers turned out to be the cause. The mistake cost the tomato industry $150 million, and consumer demand for tomatoes has still has not returned to pre-outbreak levels.

By the way, Brown’s “good” bacteria appear in early testing to cause humans no harm. Brown and his colleagues plan to test them on tomatoes grown in research settings during the winter. If that goes well, further testing in the field would follow.

The National Heart, Lung, and Blood Institute has shut down a trial designed to compare cardiac arrest resuscitation strategies used by emergency medical technicians after an analysis of preliminary data revealed the newer strategies were ineffective.

The obliquely named study, “Resuscitation Outcomes Consortium Prehospital Resuscitation using an Impedance valve and Early versus Delayed” looked at a pair of new strategies.

The first one involved using an impedance threshold device to improve circulation during CPR, supposedly by enhancing changes in chest pressure.  The device featured a valve attached to breathing tubes that are normally inserted by EMTs during the course of CPR. It didn’t work.

The second part of the trial was designed to assess whether different CPR protocols had an impact on survival. In the so-called early protocol, EMTs performed CPR until they could analyze the victim’s heart rhythm (usually 30-90 seconds).

In the late protocol, techs performed CPR for at least 3 minutes before assessing the victim’s heart rhythm. Defibrillation was used when indicated. Neither strategy proved superior to the other.

After reviewing data from 11,500 cases, the trial’s Data and Safety Monitoring Board determined that continued enrollment of new patients was not going to change the disappointing results. Soon thereafter, the NHLBI turned out the lights.

The researchers agreed to continue monitoring survivors for up to 6 months. A final report is due out next spring.

“We will continue to search for new ways to save lives in the precious few moments after cardiac arrest – and evaluate the benefits and risks of commonly used practices,” Susan Shurin, deputy director of the NHLBI, said resolutely.

Physicians have quipped for years that HMG CoA Reductase inhibitors—the cholesterol-busters better known as “statins,” ought to be put in the nation’s drinking water.

After all, they have an excellent safety profile, profoundly beneficial effects on serum cholesterol and cardiovascular mortality, and may even work against sepsis and prostate cancer.

The quip is likely to be heard even more nowadays, because a study by Meredith VanderMeer and colleagues from the Oregon Department of Public Health has shown that patients who were hospitalized for seasonal (not H1N1) flu–and who by coincidence were taking statins–had a lower risk of dying from the infection.

VanderMeer reported her team’s findings at the annual meeting of the Infectious Diseases Society of America.

In their study of 2,800 people hospitalized for flu complications, 801 patients were taking statins for high cholesterol at the time of admission. Only 17 of of them died in the hospital or within 30 days of discharge. In the remaining 1999 patients who were not taking statins, 64 died.

The difference in mortality, 2.1% vs. 3.2%, amounted to a statistically significant 54% reduction, and persisted after controlling for confounding factors such as age and the use of antiviral drugs.

Patients in the study were taking a variety of statins, including Crestor, Lescol, Lipitor, Mevacor, Pravachol, and Zocor. It was not clear whether any one of them was associated with more beneficial effects than the others.

The data for the study was pulled from the CDC’s Emerging Infections Program and covered the 2007-2008 influenza season (again, not H1N1).

According to VanderMeer, the link between statins and decreased seasonal flu mortality is not entirely surprising. Flu complications like pneumonia are caused by inflammation, and statins have anti-inflammatory effects.

VanderMeer suggested that a randomized controlled trial might help confirm her teams’ findings.

When Thai and US Army scientists announced last month that their experimental HIV vaccine reduced the risk of contracting the disease by 31%, it caused quite a stir. After all, every one of the 100 or so previous HIV vaccine trials over the last 20 years had failed completely.

Alas, a second analysis of the $105 million study that was released weeks after the announcement suggests the apparent, moderate benefit may have been caused by a statistical fluke.

Worse yet, it turns out that the results of the second analysis were available to the scientists when they announced their original findings.

“We thought very hard about how to provide the clearest, most honest message,” said Jerome Kim, an Army scientist involved with the study. “We stand by the fact that this is a vaccine with a modest protective effect.”

Kim’s team based its initial announcement on a “modified intent to treat analysis,” which includes all volunteers that enrolled in the study, whether they received the full course of the vaccine or not. Such analyses reflect real world situations in which some people don’t show up for all shots in the vaccine sequence.

Using this analysis, the scientists determined that there was only a 3.9% chance that the observed 31% reduction in HIV among the vaccine-treated group was caused by a simple statistical fluke…in scientific parlance, this is considered to be a borderline significant result.

The second, so-called “per protocol” analysis included just the study participants that received all vaccines in the regimen at the right time.

Such analyses normally corroborate intent to treat findings, but for unknown reasons, it did just the opposite in this study. It suggested there was a 16% chance the results could have been due to chance alone—far too high to support claims that the vaccine was efficacious.

Some AIDS activists and scientists believe the vaccine merits further study, but worry that the botched announcement might undermine support for the vaccine and HIV vaccine trials generally.

“I would have preferred to have seen both results straight up. It might spring back on (the scientists), and that would be unfortunate,” Mitchell Warren, director of the AIDS Vaccine Advocacy Coalition said.

Looking for another reason to avoid the Greasy Spoon on your lunch break?

Oxford University scientists have provided a doozy. In their study, rats receiving a fat-laden diet exhibited a 50% reduction in exercise capacity and diminished cognitive skills after just 9 days.

The findings could have implications for Average Joes who eat Sloppy Joes for lunch, athletes in search of an edge, and people at risk for metabolic syndrome and diabetes, say the authors who published their findings in the FASEB journal.
 
“We found that rats, when switched to a high-fat diet from their standard low-fat feed, showed a surprisingly quick reduction in their physical performance,” lead author Andrew Murray told BurrillReport.
 
The physiology behind the observations is fairly well understood. Exercise endurance is a function of the amount of oxygen that can be delivered to muscles and the efficiency with which muscles can extract the energy contained within the chemical bonds of the nutrients supplied to them (a process known as oxidation)

Fat oxidation is less efficient than the oxidation of simple carbohydrates like glucose.

For their study, Murray and Co. fed 42 rats a standard diet containing 7.5% fat, and measured exercise capacity as the maximal time they were able to run on a treadmill. They assessed short-term memory in the subjects using a maze task.

The scientists then switched half the rats to a diet in which 55% of the calories were derived from fat and reassessed the rats’ endurance and cognitive abilities.

Junk food diets can easily approach the 55% fat content used by the scientists.
 
By day 9, rats on the high fat diet managed to run only half as far as their counterparts. They were also making mistakes about 17% earlier in the maze task, suggesting diminished cognitive skills.

Cal Tech scientists may have figured out why some people have a notably annoying tendency to get too close during conversations, on subway trains or in restrooms.

The culprit turns out to be a malfunction in an almond-sized structure known as the amygdala, which is located in both temporal lobes of the brain. The amygdala processes negative emotions like anger and fear, but its role in social interaction had not previously been studied.

Daniel Kennedy, Ralph Adolphs and colleagus made the association by studying a 42-year-old woman known as SM, who has severe, isolated damage to her amygdala.

The scientists had known that SM couldn’t recognize fear in the expressions of others, or judge their trustworthiness, and had shown these abnormalities to be caused by her amygdala lesions.
 
While observing SM over time, Adolphs also noticed that she seemed to be too friendly, and frequently violated what others perceived to be their own personal space.

“She is extremely friendly, and she wants to approach people more than normal. It’s something that immediately becomes apparent as you interact with her,” Kennedy told BurrillReport.
 
So the scientists decided to compare SM’s sense of personal space to normal volunteers using the stop-distance technique, in which subjects approach a person until they reach a point where they feel most comfortable, and this distance is recorded.

Among the normal volunteers, the mean preferred distance was about 2 feet, but SM came in much tighter than that, about a foot. And unlike normal subjects who reported feeling uncomfortable when the experimenter approached to a distance within their preferred range, SM never became uncomfortable.

Even cheek to cheek, she was relaxed, and her feelings changed not a whit regardless of who the experimenter was or how well she knew them.

The write-up appears in Nature Neuroscience.

Java junkies rejoice!

New studies suggest that caffeine reduces cerebral beta amyloid deposits and improves memory and overall cognitive function in aged mice genetically altered to develop a murine form of Alzheimer’s disease.

What is more, reductions in levels of the protein marker and the improved behavioral performance showed up after the mice received the equivalent of just 2 Grande Starbucks per day for 2 months.

To reach these conclusions, Gary Arendash and colleagues at the University of South Florida studied 55 mice.

After cognitive testing confirmed the little fellows were losing their marbles, the scientists added caffeine to the drinking water of half the subjects. The unlucky others just got the water.

After 2 months, the mice that received the Joe outperformed their counterparts on a battery of  memory and cognitive skills, and in fact their recall essentially matched that of normal, age-matched mice.

The scientists then showed that brains of the caffeinated mice had nearly 50% less beta amyloid, the notorious plaque-building protein that is the pathologic sine qua non of Alzheimer’s disease.

“The findings provide evidence that caffeine could be a viable treatment for established Alzheimer’s disease, and not simply a protective strategy,” Arendash told BurrillReport. “Caffeine is a safe drug for most people, it easily enters the brain, and it appears to directly affect the disease process.”

Arendash’s group performed follow-up experiments which suggested the wonder drug appears to work by down-regulating the process by which beta amyloid is produced, and by reducing cerebral inflammatory changes that stimulate beta amyloid production.

The write-up appears in the Journal of Alzheimer’s Disease. The scientists hope to begin human trials shortly. Getting people to volunteer for the studies is not expected to be problematic.