Diabetes increases risk of death in breast cancer patients

Breast cancer patients are nearly 50 percent more likely to die of any cause if they also have diabetes, according to a comprehensive review of research conducted by Johns Hopkins physicians.

Peairs says her research suggests that diabetics diagnosed with breast cancer may get less effective treatment because practitioners may be concerned about these patients suffering more side effects from chemotherapy or radiation treatments as a result of the metabolic condition. Patients also may be more likely to be hospitalized, get infections, and/or become anemic ??” complicating their care. Peairs says the higher death rate may also be linked to the fact that they come to breast cancer treatment less healthy than their counterparts without diabetes, which is associated with obesity, high cholesterol and high blood pressure.

Women with diabetes may also be at greater risk of chemotherapy-related toxicity, which may explain ??” and even justify ??” some of the less aggressive treatment, she says.

Peairs says more research should reveal whether increased insulin production in type 2 (adult onset) diabetics contributes to worse outcomes among diabetic breast cancer patients. Small studies suggest that some diabetes drugs may be associated with worse outcomes for cancer patients while other medications may actually improve survival.

She noted that the popular drug metformin, which makes diabetes patients more insulin-sensitive thereby lowering the amount of unused insulin in the body, may be associated with better survival outcomes.

SOURCE Johns Hopkins University School of Medicine

Modifiable and non-modifiable lifestyle factors influence breast cancer risk

Many risk factors for breast cancer are well studied and documented. Thus, scientists are sure by now that early first menstrual period, late onset of menopause and a family history of breast cancer are associated with an increased breast cancer risk.

Of the modifiable lifestyle factors, it is primarily hormone replacement therapy and a lack of physical activity which increase a woman’s risk of developing breast cancer. Alcohol consumption and overweight were found to have less influence on breast cancer risk. Thus, 19.4 percent of invasive postmenopausal breast cancer are attributed to hormone replacement therapy; 12.8 percent to a lack of physical activity. Both factors together are responsible for 29.8 percent of breast cancer cases. When the investigators took a separate look at the group of patients whose tumors have receptors for sex hormones (hormone receptor-positive breast tumors), they determined an even higher value of 37.9 percent. The study leaders emphasize that these results reflect the situation in Germany with our typical lifestyle and may differ in countries with other lifestyles.

Non-modifiable factors such as family history or age at first and last menstrual period account for 37.2 percent in total of all malignant postmenopausal breast cancers. "That means that two factors which each woman has in her own hands are responsible for a similar number of postmenopausal breast cancer cases as the non-modifiable factors," Karen Steindorf says. "If behavioral changes in these two areas could be brought about, almost 30 percent of breast cancers after menopause could be prevented." Therefore, the DKFZ researchers recommend women to take more exercise and to refrain from hormone replacement therapy, unless it is absolutely necessary.

Source: Helmholtz Association of German Research Centres

Severe asthma in early childhood may lead to premature loss of lung function during adolescence: Study

Severe asthma in early childhood may lead to premature loss of lung function during adolescence and more serious disease during adulthood, researchers at Emory University School of Medicine report. Early identification and treatment of children with severe asthma is important to help stem asthma progression.

The authors found that children with severe asthma reported a higher frequency of daily symptoms and hospitalization during the previous year despite higher doses of ICS and controller medication, and that they had significantly lower lung function when compared to children with mild-to-moderate asthma. Additionally, they noted that daily asthma symptoms such as coughing and wheezing and sensitization to aeroallergens during the initial evaluation were strong predictors of declines in lung function of more than one percent per year.

The authors conclude that children with severe asthma have a premature loss of lung function during the adolescent years that is associated with an increased frequency of wheezing and asthma symptoms and greater allergic sensitization during childhood. Further studies are needed to determine whether the loss of lung function is due to a slower rate of lung growth or to progressive changes in the lung tissues, and to explore the mechanisms that control the responses of severely asthmatic children to ICS treatment.

Source: Emory University

Study shows new cardio-pulmonary resuscitation technique increases long-term survival of patients

A study led by Dr. Tom P. Aufderheide, professor of emergency medicine at The Medical College of Wisconsin, shows an alternative method of cardio-pulmonary resuscitation increases long-term survival of patients.

The new technique uses two devices simultaneously to increase circulation. One is a handheld device that attaches with a small suction cup to the patient’s chest. After each compression, the suction cup allows the chest to be lifted up, stimulating blood flow. The second device, called an impedance threshold device, attaches to the patient’s airway using a facial mask or breathing tube. When the chest lifts upward, the impedance threshold device prevents air from rushing into the lungs. That creates a vacuum inside the chest and helps refill the heart after each compression. Researchers found in each compression-decompression cycle, the heart and brain receive nearly three times more blood flow when compared with standard CPR.

A total of 813 standard CPR patients and 840 intervention patients were analyzed in the study. Researchers found 6% of the standards CPR patients survived to hospital discharge with favorable neurologic function. That compares with 9% in the intervention group (improvement of survival chance 53% in intervention group). The same proportions of patients in each group survived to one year.

"Based on our findings, active compression-decompression CPR with augmentation of negative intrathoracic pressure should be considered as an alternative to standard CPR to increase long-term survival after cardiac arrest," said Dr. Aufderheide.

Source: Medical College of Wisconsin

Time-lapse technique can show cellular-level changes within deep brain regions: Study

Changes within deep regions of the brain can now be visualized at the cellular level, based on research on mice, which was funded by the National Institutes of Health. Published Sunday in Nature Medicine, the study used a groundbreaking technique to explore cellular-level changes over a period of weeks within deep brain regions, providing a level of detail not possible with previously available methods.

Investigators focused on two brain regions within the study, the hippocampus and striatum. The striatum, a brain region important for motor function and habit formation, is also a major target for abused drugs. Some researchers believe that a shift in activity within the striatum is at least partly responsible for the progression from voluntary drug-taking to addiction. This new technique could allow a better understanding of how these processes occur at the cellular level, leading to insights into mechanisms underlying addictive behaviors.

"The results should now allow neuroscientists to track longitudinally in the living brain the effects of drugs of abuse at the levels of neural circuitry, the individual neuron, and neuronal dendrites," said Dr. Mark Schnitzer, corresponding author for the article. "For example, our imaging methods work well in the dorsal striatum, which we have followed with microscopic resolution over weeks in the live brain. This should permit researchers interested in the reward system to address a range of issues that were previously out of reach."

Source: NIH/National Institute on Drug Abuse

AMBR sensor measures growth and drug susceptibility of bacterial cells without use of microscope

With an invention that can be made from some of the same parts used in CD players, University of Michigan researchers have developed a way to measure the growth and drug susceptibility of individual bacterial cells without the use of a microscope.

"You can basically tell, within minutes, whether or not the antibiotic is working," said Kinnunen.

In the near future, "we expect it will be possible to make the determination even quicker," said graduate student Irene Sinn, the paper’s other lead author. "This is something we are actively working on."

The device also can be used for monitoring the growth and drug susceptibility of other types of cells, said Kinnunen. "The sensor is very sensitive to small changes in growth, so this method can be applied to any applications in the microscale or nanoscale where there are small changes in size. That includes the growth of yeast and cancer cells as well as bacteria."

The technology could have far-reaching implications, said McNaughton.

"At Life Magnetics we are very excited and optimistic about leveraging the single cell sensitivity of the AMBR technology to develop a product that will determine the best antimicrobial in hours instead of days," he said. "This will have a dramatic positive impact for patients and for the health system, cutting costs and saving lives. Inappropriate therapy and the overuse of antimicrobials are large contributors to the problem of increased resistance in bacteria. In fact, with superbugs such as MRSA causing every year in the U.S. more deaths than HIV/AIDS, it is no surprise that the Centers for Disease Control and Prevention considers antimicrobial resistance to be among the most pressing health problems. Our technology is designed to attack that problem."

Source: University of Michigan

MicroRNA-29 molecule makes brain cells resistant to programmed cell death

Researchers at the University of North Carolina at Chapel Hill have discovered a molecule that can make brain cells resistant to programmed cell death or apoptosis.

They then decided to pinpoint where exactly this molecule played a role in the series of biochemical events leading to cell death. The researchers looked at a number of steps in apoptosis and found that miR-29 acts at a key point in the initiation of apoptosis by interacting with a group of genes called the BH3-only family. Interestingly, the microRNA appears to interact with not just one but as many as five members of that family, circumventing a redundancy that existed to allow cell death to continue even if one of them had been blocked.

"People in the field have been perplexed that when they have knocked-out any one of these members it hasn’t had a remarkable effect on apoptosis because there are others that can step in and do the job," said Deshmukh. "The fact that this microRNA can target multiple members of this family is very interesting because it shows how a single molecule can basically in one stroke keep apoptosis from happening. Interestingly, it only targets the members that are important for neuronal apoptosis, so it may be a way of specifically preserving cells in the brain without allowing them to grow out of control (and cause cancer) elsewhere in the body."

Deshmukh is currently developing mouse models where miR-29 is either "knocked-out" or overactive and plans to cross them with models of Alzheimer’s disease, Parkinson’s disease and ALS to see if it can prevent neurodegeneration. He is also actively screening for small molecule compounds that can elevate this microRNA and promote neuronal survival.

SOURCE University of North Carolina at Chapel Hill

Study may help develop novel ways to combat lipotoxic cardiomyopathy, related heart disease

A team led by Rolf Bodmer, Ph.D. at Sanford-Burnham Medical Research Institute recently unraveled an alternative pathway to lipotoxic cardiomyopathy in fruit flies – a genetic mechanism that occurs independently of a diet high in fat.

Since overactive SREBP seems to be the cause of heart disease in this system, can it be targeted to reduce heart disease? The researchers addressed this question by inhibiting SREBP or its fat-synthesizing target genes through genetic manipulation. In doing so, they were able to restore fat balance and rescue PE-deficient flies from heart malfunction. These beneficial effects were also achieved by reducing SREBP in just the heart, rather than the whole fly. As a result, the flies were still obese, but their hearts functioned normally. These findings further underscore the importance of SREBP in excess fat-related heart diseases, like lipotoxic cardiomyopathy.

"Here we identified a new metabolic pathway that exhibits striking similarities to obesity- and diabetes-related heart failure in humans," explained Dr. Bodmer, professor and director of the development and aging program at Sanford-Burnham and senior author of the study. "This information might now allow us to interfere with the toxic effects of high fat in the heart by directly manipulating these genes in the heart muscle."

Source: Sanford-Burnham Medical Research Institute

Magnetic maneuverable capsule safe and well-tolerated in the stomach

A study from researchers in Germany showed that magnetic maneuvering of a modified capsule endoscope in the stomach of healthy volunteers under clinical conditions is safe, well-tolerated, and technically feasible. Maneuverability of the capsule within the stomach was excellent and visualization of the gastric mucosa, the inner lining of the stomach, was satisfactory in the majority of subjects.

The study participants swallowed the MMC and sherbet powder to distend the stomach, which flattens the folds of the stomach. The external magnetic paddle was used to manipulate the MMC within the stomach. MMC responsiveness was evaluated on a screen showing the MMC film in real time. The main outcome measurements were safety and tolerability, time the MMC remained in the stomach, its responsiveness to the magnetic paddle, and the area of the stomach lining visualized.

Results

The MMC was always clearly attracted by the magnetic paddle and responded to its movements. In seven participants, maneuverability was graded as excellent because the MMC followed the rotating and tilting movements of the magnetic paddle smoothly. It remained in the stomach for approximately 39 minutes (plus or minus 24 minutes). In seven subjects, both the cardia (part of the stomach immediately adjacent to the esophagus) and the pylorus (part of the stomach through which contents are emptied into the small intestine) were inspected and 75 percent or more of the gastric mucosa was visualized (greater than or equal to 50 percent in all of the remaining subjects). The researchers noted that a learning curve was clearly recognizable (identification of MMC localization, intended movements). Some limitations of the study included small amounts of fluid that blocked the view of an area of the stomach called the fundus and gastric distention was not sufficient to flatten all gastric folds. There were no adverse events.

Study participants completed a questionnaire after the procedure, asking about difficulties swallowing, pain or other complaints. Nine participants reported no complaints and one reported mild complaints of feeling pressure. The researchers concluded that remote control of the MMC in the stomach of healthy volunteers using a handheld magnet is safe and feasible. Responsiveness of the MMC was excellent, and visualization of the stomach lining was good, although not complete, in the majority of subjects. The system appeared to be clinically valuable and should be developed further.

Source: American Society for Gastrointestinal Endoscopy

Antioxidants may cause fertility problems in females

Antioxidants are sold over the counter everywhere. They’re added to food, drink and face cream. But according to Prof. Nava Dekel of the Biological Regulation Department, we still don’t have a complete understanding of how they act in our bodies. New research by Dekel and her team, recently published in the Proceedings of the National Academy of Sciences USA (PNAS), has revealed a possible unexpected side effect of antioxidants: They might cause fertility problems in females.

Among other things, these results help fill in a picture that has begun to emerge in recent years of fertility and conception, in which it appears that these processes share a number of common mechanisms with inflammation. It makes sense, says Dekel, that substances which prevent inflammation in other parts of the body might also get in the way of normal ovulation, and so more caution should be taken when administering such substances.

Much of Dekel’s research has focused on fertility — her previous results are already helping some women become pregnant. Ironically, the new study has implications for those seeking the opposite effect. Dekel: ‘On the one hand, these findings could prove useful to women who are having trouble getting pregnant. On the other, further studies might show that certain antioxidants might be effective means of birth control that could be safer than today’s hormone-based prevention.’

Dekel and her team are now planning further studies to investigate the exact mechanics of this step in ovulation and to examine its effect on mice when administered in either food or drink. In addition, they plan to collect data on the possible link between females being administered antioxidant supplements and the difficulty to conceive.

Source: Weizmann Institute of Science