These decisions would apply to treatment of cancer that has already spread beyond the prostate gland or that has recurred after initial treatments, such as surgery or radiation. Patients with this more advanced prostate cancer receive a therapy called androgen ablation, which inhibits production of testosterone – the culprit that allows a tumor to keep growing.

Though the model’s outcomes remain theoretical at this point, the researchers have developed enough of a system to show that their incorporation of some personalized data – details about a patient’s tumor cell characteristics in particular – would give doctors more than they currently have to work with in making decisions about this stage of treatment.

“The model in its current form is proof of the concept that we can capture all of these different outcomes that are observed clinically. But we still need to refine the model with as much individual data as we can obtain,” said Harsh Jain, a postdoctoral fellow in Ohio State University’s Mathematical Biosciences Institute and lead author of the study.

“We envision that this model would be useful for clinicians who could keep feeding the equations with data about how a patient is responding to therapy, which would offer clues about how his cancer cells are mutating. Once you have an idea about that for the short or medium term, the model could predict the optimal therapy for that patient,” Jain said.

The model is described this week in the online early edition of the Proceedings of the National Academy of Sciences. Jain conducted the work with co-authors Steven Clinton, professor, and Arvinder Bhinder, assistant professor-clinical, in Ohio State’s division of medical oncology, and Avner Friedman, a Distinguished University Professor at Ohio State.

Prostate cancer is diagnosed in about 240,000 American men and leads to about 34,000 deaths each year, according to the National Cancer Institute.

The treatment of this cancer in its more advanced stages brings about chemical castration by targeting one of several mechanisms involved in the production of testosterone. In most patients, cancer cells develop castration resistance over time – on average, between 1½ and two years after the start of treatment. However, the overall range of resistance development spans from a few months to more than 10 years.

Jain said that some scientists have proposed that this treatment leads directly to castrate-resistant disease because once testosterone is removed from the body, mutant cancer cells that can survive in a no- or low-testosterone environment are able to take over the tumor.

Currently, continuous treatment to eliminate testosterone is the standard of care. But because clinicians know castration resistance is inevitable, a new approach is under study. A national clinical trial is assessing the benefits and risks of intermittent androgen ablation – keeping patients on the drugs until symptoms improve, and then giving men time off from the medication until the disease begins to progress again.

The math model developed by Ohio State scientists suggests that based on average clinical data currently available, such intermittent therapy could actually accelerate the development of castration resistance.

“In the same way that intermittent use of antibiotics gives a chance for bacteria that are resistant to the drug to take over, you might actually end up with intermittent anti-androgen therapy even more positively selecting for mutating cancer cells,” Jain said.

However, the averages don’t always apply, which is why the scientists are pursuing a system of differential equations to account for individual differences. For example, the “normal” levels of prostate-specific antigen, or PSA, in men’s blood cover a fairly broad range, Jain noted. Yet the PSA test remains the most common screening method for prostate cancer, and is used to gauge the effectiveness of treatments in advanced stages, as well.

“The PSA ranges are massive. It’s a very heterogeneous thing,” Jain said. “When we are talking about cancer, our point is that those variables should be personalized. Everyone’s cancer grows differently.

“There are a lot of questions. If you take an intermittent therapy route, how do you decide the scheduling of treatment? Is it based solely on PSA levels? Shouldn’t there be some incorporation of personal patient characteristics into these treatment decisions? Can you identify a subgroup of patients who are predicted to respond well to this, or are there conditions when one treatment vs. another could actually make things worse?”

Math offers some answers. The model’s foundation is based on existing animal and human data on prostate cancer characteristics. Beyond that, the researchers have selected parameters to plug into the equations that more specifically detail what could be going on in an individual tumor: cancer cell growth rates, cancer cell death rates, the level of activation of PSA in tumor cells, and how quickly one person’s PSA can travel from the prostate to the bloodstream.

The scientists even took into account the competitive power of individual types of cancer cells – for example, some mutated cancer cells aren’t as strong as their normal cancer cell counterparts. In those cases, the math model predicts, the best treatment option would be intermittent therapy because the stronger normal cancer cells would keep mutant cells in check during time off from the medication. With the cancer consistently dominated by cells that rely on the presence of testosterone, the treatment would continue to target those stronger cells that respond to androgen ablation therapy, Jain explained.

“That’s an important question with any therapy – is it making things better or worse in terms of allowing mutated cells to take over?” he said.

Jain and colleagues are now working to boost the model’s power by adding parameters that account for the blood vessel architecture in prostate tumors, a major indicator of how persistent the cancer will be. They also plan to add hundreds of individual patients’ case study data to make its predictions even more authentic.

FDA’s action will provide surgeons with a minimally-invasive option for repair of aortic endografts (endovascular grafts) that are not properly positioned. Aortic aneurysms can, over time, become weak and result in a life-threatening rupture. The endograft is placed inside the aorta to seal off the aneurysm and direct blood away from it.

The Aptus EndoStapling System is a cassette of nickel-cobalt corkscrew-shaped staples that is loaded into a long, thin, tube-like delivery catheter. The catheter is inserted into an artery in the leg and directed through the arteries to the failed endograft. Using a controller on the handle of the catheter, the surgeon applies one staple at a time around the top edge of the endograft to anchor the device and repair the endograft-artery seal.

“Leakage between the top end of the endograft and the aorta wall is a known complication of endograft implants that can be successfully treated,” said Christy Foreman, director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health. “The Aptus EndoStapling System provides a less invasive option than open surgery to access and repair these leaks.”

The FDA reviewed data for the Aptus EndoStapling System through the de novo reclassification process, a regulatory pathway for low- to moderate-risk medical devices that are novel and not comparable to an already legally marketed device.

FDA granted the de novo petition for the EndoStapling System based on review of data from 154 patients who were implanted with 810 EndoStaples. Patients were monitored with routine followup CT scans. After a year, none of the EndoStaples had fractured and no patients experienced endograft movement (migration); one subject needed an additional intervention to address an endoleak.

The Aptus EndoStapling System is for use in patients whose endovascular grafts have moved, exhibit endoleaks, or are at risk for these complications and additional intervention is needed to reattach the graft and seal off the aneurysm.

The Aptus EndoStapling System is manufactured by Aptus Endosystems Inc. of Sunnyvale, Calif.

In a nested case-control study of 327 non-smoking FDNY 9/11 rescue workers, metabolic syndrome biomarkers measured within six months of exposure to WTC dust predicted decline of forced expiratory volume in one second (FEV1) over the next six years.

“Study participants with dyslipidemia, elevated heart rate or elevated leptin levels had a significantly increased risk of developing abnormal lung function during follow-up,” said Anna Nolan, MD, MS, assistant professor of Medicine and Environmental Medicine at NYU Langone Medical Center. “In contrast, elevated amylin levels reduced the risk of developing abnormal FEV1 levels.”

The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

This case-control study was nested within a larger longitudinally followed cohort. All subjects had normal lung function prior to 9/11. Cases (n = 109) were defined as having FEV1 values below the lower limit of normal at follow-up, while controls (n = 218) were defined as having FEV1 at or above the lower limit of normal. Biomarkers were available for 71 cases and 166 controls. Lung function in cases continually declined in the median 28 months between baseline and follow-up examinations, while lung function improved in controls.

In a model adjusting for age, race, body mass index and WTC arrival time, dyslipidemia (triglycerides≥150mg/dL and HDL<40mg/dL) increased the odds of being a case three-fold, elevated heart rate (≥66 bpm) increased the odds more than two-fold, and elevated leptin (≥10,300 pg/mL) increased the odds three-fold. Elevated amylin levels (≥116 pg/mL) decreased the odds of being a case by 84 percent. “This is the first report in humans showing an association between amylin and lung function,” Dr. Nolan said. “There are amylin receptors in the lungs, and amylin has been shown to reduce leptin resistance. The protection offered by amylin in this study may have been mediated by these effects.”

“These findings suggest that systemic inflammation, a hallmark of the metabolic syndrome, may play a role in promoting lung function impairment in patients with particulate exposure,” Dr. Nolan said. “Given the high prevalence of the metabolic syndrome in industrialized nations and the rising incidence in developing nations with high ambient particulate levels, the relationship between these disorders is of considerable importance.”

The study had a few limitations. Use of a single cohort of rescue workers limits extrapolation of these results to other cohorts. There was no unexposed control group in this study, so replication of these findings in populations with and without exposure to particulate matter is needed. Finally, other possible causes of lung dysfunction were not explored.

“Our findings in WTC rescue workers highlight the importance of conducting rapid medical monitoring and sample banking following a disaster,” said Dr. Nolan. “If we can identify individuals at greater risk of developing lung function impairment, we can initiate appropriate interventions earlier.”

Avastin will still remain on the market as an approved treatment for certain types of colon, lung, kidney and brain cancer (glioblastoma multiforme).

“This was a difficult decision. FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use,” Dr. Hamburg said. “After reviewing the available studies it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks. Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life.”

Avastin’s risks include severe high blood pressure; bleeding and hemorrhaging; heart attack or heart failure; and the development of perforations in different parts of the body such as the nose, stomach, and intestines.

Today’s decision, outlined in Dr Hamburg’s 69-page opinion, involves Avastin used in combination with the cancer drug paclitaxel for those patients who have not been treated with chemotherapy for their form of metastatic breast cancer known as HER2 negative. This indication must now be removed from Avastin’s product labeling.

Dr. Hamburg’s decision is based on an extensive record, which includes thousands of pages submitted to a public docket, data from several clinical trials and the record from a two-day hearing held in June, 2011.

Avastin was approved for metastatic breast cancer in February 2008 under the FDA’s accelerated approval program, which allows a drug to be approved based on data that are not sufficiently complete to permit full approval. The accelerated approval program provides earlier patient access to promising new drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted. If the clinical trials do not justify the continued approval of the drug or a specific drug indication, the agency may revoke its approval. In this case, the accelerated approval was based on promising results from one study that suggested that the drug could provide a meaningful increase in the amount of time from when treatment is started until the tumor grows or the death of the patient.

After the accelerated approval of Avastin for breast cancer, the drug’s sponsor, Genentech, completed two additional clinical trials and submitted the data from those studies to the FDA. These data showed only a small effect on tumor growth without evidence that patients lived any longer or had a better quality of life compared to taking standard chemotherapy alone – not enough to outweigh the risk of taking the drug.

FDA’s Center for Drug Evaluation and Research, which is responsible for the approval of this drug, ultimately concluded that the results of these additional studies did not justify continued approval and notified Genentech it was proposing to withdraw approval of the indication.

Genentech did not agree with the Center’s evaluation of the data and, following the procedures set out in FDA regulations, requested a hearing on the Center’s withdrawal proposal, with a decision to be made by the Commissioner. That two-day hearing, which took place June 28-29, 2011, included recommendations from the FDA’s Oncologic Drugs Advisory Committee (ODAC), voting 6-0 in favor of withdrawing approval of Avastin’s breast cancer indication. After the hearing, the public docket remained open until Aug. 4, 2011. (In an earlier meeting of the ODAC, that committee had voted 12-1 in favor of the removal of the breast cancer indication from the Avastin label).

“FDA is committed to working with sponsors to bring promising cancer drugs to market as quickly as possible using tools like accelerated approval,” Dr. Hamburg said. “I encourage Genentech to consider additional studies to identify if there are select subgroups of women suffering from breast cancer who might benefit from this drug.”

“Anecdotally, many researchers have observed that HDL levels may be lower in states of inflammation, such as rheumatoid arthritis, psoriasis and even obesity,” said lead study author Nehal Mehta, MD, MSCE, director of Inflammatory Risk in Preventive Cardiology at Penn. “However, these new findings suggest that in addition to lower levels, chronic inflammation associated with conditions like psoriasis may change the composition and decrease the function of HDL as well.”

In the current studies, researchers enrolled 78 patients with psoriasis and 84 control subjects. In the first study, the authors measured fasting lipid levels and examined the number and size of cholesterol particles using nuclear magnetic resonance (NMR) spectroscopy. This analysis revealed that patients with psoriasis had a higher number of smaller LDL particles, or “bad” cholesterol, which was independent of traditional risk factors and obesity. “It was striking that the NMR profiles from patients with psoriasis resembled those seen in patients with diabetes, and that these patients with psoriasis had otherwise normal traditional lipid panels” Dr. Mehta added.

In the second study, the researchers measured HDL efflux, which is the ability of a patient’s HDL to remove cholesterol from cells involved in atherosclerosis. This process, known as ‘reverse cholesterol transport’, is why HDL may have protective properties. In a previous study, researchers at Penn have demonstrated that measuring HDL efflux capacity may be a more effective barometer of protection from heart disease than measuring HDL levels alone.

In this same group of patients who had normal cholesterol levels compared to controls, patients with psoriasis demonstrated dramatically reduced HDL efflux capacity compared to control patients. This negative association observed between psoriasis and HDL efflux persisted after adjusting for traditional lipid levels and other traditional risk factors, including body mass index (BMI).

“Patients with psoriasis had an approximate 25 percent reduction in the HDL efflux capacity than the controls, despite their relatively normal overall lipid profiles which leads to the question of whether function is more important than concentration in chronic inflammatory states” Dr. Mehta noted.

The new findings may provide a critical clue to the link between psoriasis and heart disease, but the researchers say larger studies are needed to validate their findings. Joel M. Gefland, MD, MSCE, assistant professor of Dermatology and Epidemiology, and a senior author on the studies, said “We’ve been able to show that psoriasis is an important risk factor for vascular disease, and now we may finally be able to identify and ultimately treat the pathways by which psoriasis increases these risks.”

“We have shown that a particular marker on the T-cells, PD-1, was found significantly more frequently in those young patients in whom relapses were about to occur,” says lead author, Dr. Hugo Soudeyns, an investigator at the Sainte-Justine University Hospital Research Center, affiliated with Université de Montreal. “PD-1 is also an indicator of ‘T cell exhaustion’, a process whereby T cells lose their capacity to multiply and are less effective at fighting viruses and cancer cells.”

Window of vulnerability

Dr. Soudeyns and his colleagues analyzed blood samples from young children who received an umbilical cord blood transplant for the treatment of blood disorders, including leukemia. They were particularly interested in studying the three to six month time period post-transplantation, when the children were most susceptible to both relapse and infection. During this time, expression of the PD-1 marker peaked, suggesting that many of these T cells were at the end of their life cycle and thus less effective.

“Our findings suggest that measurement of exhaustion markers such as PD-1 could serve as an early predictor of leukemic relapse – a very serious complication,” says Dr. Soudeyns. “Our next step is to repeat these experiments in larger groups of patients.”

Highlights

Diabetic patients with kidney failure benefit the most when their hemoglobin A1C levels, which reflect blood glucose levels, are between 7% and 8%.

For diabetics who need dialysis, hemoglobin A1C levels of 8% or greater or less than 7% put them at increased risk of dying prematurely compared to patients with levels between 7.0% and 7.9%.

Two separate studies presented during the American Society of Nephrology’s Annual Kidney Week agree that diabetics with kidney failure shouldn’t lower their blood glucose levels as much as diabetics without kidney failure.

For most patients with diabetes, taking medication to lowering blood levels of hemoglobin A1C, which reflect average blood glucose levels, to <7% can lower their risk of developing certain complications. Sylvia Paz Ramirez, MD (Arbor Research Collaborative For Health) and her colleagues wondered whether this holds true for diabetic patients who have developed kidney failure.

The researchers analyzed data from 8,437 dialysis patients from 12 countries who had diabetes. They found that the lowest risk of death during the study occurred when hemoglobin A1C levels were between 7% and 8%. Both high and low levels were linked with increased rates of death, particularly for patients with levels of 9% or higher or less than 5%. Among patients with A1C levels below 7%, death rates were higher among patients taking diabetes medications.

In a similar study, Miklos Molnar MD, PhD (Semmelweis University, in Budapest, Hungary) and his team examined death rates among 54,757 diabetic patients treated at DaVita dialysis clinics from July 2001 through June 2006 with follow-up through June 2007. They found a link between high death rates and hemoglobin A1C levels of 8% or greater. Very low levels also increased patients’ risk of dying during the study.

These results indicate that unlike for most patients with diabetes, diabetics with kidney failure benefit the most when their hemoglobin A1C levels are between 7% and 8%, although clinical trials are needed to definitely determine the optimal range.

Parkinson’s disease is a movement disorder caused by the loss of brain cells that produce a molecule called dopamine. The primary symptoms of Parkinson’s are tremor, stiffness, slowed movement and impaired balance, and as these symptoms progress, patients may also develop difficulty walking, speaking or completing other activities of daily living. Genes play a role in Parkinson’s disease, but fewer than 10 percent of cases are due to a single gene mutation, and not all people with these mutations develop Parkinson’s, suggesting that environmental factors also contribute to the likelihood of developing the disease.

The researchers, led by Samuel Goldman, M.D., M.P.H. and Caroline Tanner, M.D., Ph.D. at the Parkinson’s Institute in Sunnyvale, Calif., collected the histories of 99 pairs of twins in which one of the pair developed Parkinson’s and the other twin did not. Since twins are so genetically similar, twin studies are especially useful in identifying environmental influences in disease. The twins were identified through the National Academy of Sciences/National Research Council World War II Veteran Twins Registry. Of the 99 pairs, half were genetically identical twins, and half were fraternal twins.

The study team assessed the twins’ lifetime work and hobby activities, specifically inquiring about occupational tasks such as electrical work, industrial machinery repair, and dry cleaning, which would potentially expose people to chemicals previously linked to Parkinson’s. The researchers also collected information on head injuries, which are suspected to increase Parkinson’s risk, and smoking history, which is reported to decrease Parkinson’s risk. Expert evaluators, unaware of which study subjects had Parkinson’s, reviewed this information and calculated lifelong exposure to six chemicals: TCE, PERC, carbon tetrachloride, n-hexane, xylene and toluene. Of these, TCE and PERC posed a notable risk for developing Parkinson’s.

“The potential importance is great, since both solvents persist in the environment and are commonly used,” said Dr. Goldman, “Parkinson’s was sixfold more common in twins exposed to TCE, and ninefold more common in twins exposed to TCE or PERC.” There was also a trend toward a tenfold increase in Parkinson’s disease in twins exposed to PERC alone.

In this study researchers looked only at occupational chemical exposure, and the association with job categories tended toward significance only for the industrial machinery repairer and industrial worker categories. However, the chemicals evaluated here are found outside industrial settings as well. PERC is the leading chemical used in garment dry cleaning. TCE is the most frequently reported organic groundwater contaminant, was once used as general anesthetic and coffee decaffeinating agent, and is still used widely as a metal degreasing agent.

TCE has also been linked to Parkinson’s by other research groups. Researchers at the University of Kentucky, Lexington, and the Kangwon National University in South Korea have reported an association between TCE and Parkinson’s in highly-exposed industrial workers, and have also demonstrated that TCE causes neurodegeneration in animal models.

The analysis described in this report expands on preliminary findings presented at the 2010 American Academy of Neurology meeting. The new paper quantifies the individuals’ exposures to the chemicals in terms of successive years and cumulative exposure over their lifetime.

Dr. Tanner notes that while the association between chemical exposure and Parkinson’s is strong, one limitation of the research is the small number of individuals studied. “It will be important to replicate these results in additional populations with well-characterized exposure histories,” she commented.

Wendy Galpern, M.D., Ph.D., program director at NINDS, agreed that replication of these results is necessary. “This epidemiologic study is a noteworthy addition to our growing understanding of the association between environmental exposures and Parkinson’s disease,” Dr. Galpern said. “The identification of specific chemicals linked to this neurodegenerative disorder may have implications for disease prevention and an improved understanding of how Parkinson’s develops.”

Each year, millions of Americans take antibiotics to fight infections. But overuse and misuse of antibiotics can change germs, allowing them to evolve resistance to antibiotics, which increases the risk of an infection for which there are limited or no treatment options. Patients who receive antibiotics can experience side effects, including allergic reactions and may be at increased risk for Clostridium difficile infection, a potentially deadly diarrheal infection.

“Antibiotic use leads to antibiotic resistance, which is a major public health problem,” said CDC Director Thomas R. Frieden, M.D., M.P.H. “Hospitals and other health care facilities should monitor the antibiotics used in their facilities. This new system is a powerful tool that will enhance providers′ ability to monitor and improve patterns of antibiotic use so that these essential drugs will still be effective in the years to come.”

The antibiotic use tracking system is part of CDC′s National Healthcare Safety Network, the nation′s premier tool for monitoring infections in health care facilities, which includes over 4,800 hospitals. CDC has funded four health departments and their academic partners to implement the tracking system in 70 hospitals. In addition, any hospital that participates in the National Healthcare Safety Network can utilize this tool by working directly with its pharmacy software vendor to transmit data electronically from drug administration or barcoding records. There is no manual entry of data, thus saving a facility time and money.

“The threat of untreatable infections is real,” says Arjun Srinivasan, M.D., who heads CDC′s Get Smart for Healthcare program. “Although previously unthinkable, the day when antibiotics don′t work in all situations is upon us. We are already seeing germs that are stronger than any antibiotics we have to treat them, including some infections in health care settings.”

CDC implements multiple strategies to address antibiotic use, including Get Smart About Antibiotics Week (Nov. 14—20, 2011). This year, CDC and its partners are teaming up to promote appropriate antibiotic use among the nation′s health care facilities and doctors′ offices to preserve the strength of existing antibiotics and prevent resistant infections. While success of these strategies has been documented over the last decade with less unnecessary prescribing for colds and sore throats, there is still room for improvement as up to half of antibiotic prescriptions are unnecessary.

The 2011 observance of Get Smart About Antibiotics Week is an international collaboration, coinciding with European Antibiotic Awareness Day and Canada′s Antibiotic Awareness Week. CDC′s Get Smart: Know When Antibiotics Workand Get Smart for Healthcare programs are designed to educate consumers and health care providers about appropriate use of antibiotics. In conjunction with Get Smart About Antibiotics Week, CDC is announcing a partnership with the Institute for Healthcare Improvement  to pilot test a tool to help hospitals implement practical strategies to improve antibiotic use. The pilot testing is currently under way in eight U.S. hospitals.

Additionally, CDC is part of the Federal Interagency Task Force on Antimicrobial Resistance. During the observance week, this task force will meet in Washington, D.C., to discuss next steps toward meeting goals of the recently revised A Public Health Action Plan to Combat Antimicrobial Resistance. Patients, health care providers, hospital administrators, and policy makers must work together to employ safe and effective strategies for improving antibiotic use.

To access a list of pharmacy software vendors who are working with CDC′s new antibiotic use tracking system, see the Society for Infectious Disease Pharmacists website at www.sidp.org.

CDC works 24/7 saving lives, protecting people from health threats, and saving money to have a more secure nation. Whether these threats are chronic or acute, manmade or natural, human error or deliberate attack, global or domestic, CDC is the U.S. health protection agency.

Now, in research at the University of Georgia, a cellular biologist and his colleagues have found that Hirano bodies may play a protective role in the progression of neurodegenerative diseases such as Alzheimer’s. And to find out why this may be happening, they have developed the world’s first transgenic mouse model that has Hirano bodies, which will open new frontiers on how these poorly understood structures may be involved with some of humankind’s most difficult-to-treat diseases.

“This work gives us a first view of the possible effects of Hirano bodies,” said Marcus Fechheimer, Josiah Meigs Professor of cellular biology at UGA. “Now we know that Hirano bodies do not kill cells and are not toxic to mice. This new model will allow us to ask whether Hirano bodies have any effect on progression of disease in the brain.”

While the research offers no cure for diseases such as Lou Gehrig’s and mad cow, it does create a new area of research into understanding how these diseases operate in the human body and why they are so difficult to treat. And the problem is vast: the Alzheimer’s Association reports there are 5.4 million sufferers of that disease in the U.S. alone.

The latest research announcing the transgenic mouse model for the formation of Hirano bodies was just published in the journal BMC Neuroscience. Co-authors with Fechheimer include Ruth Furukawa in the Fechheimer lab at UGA, as well as John Wagner and Michael Stramiello of the College of Veterinary Medicine, also at UGA; and Sangdeuk Ha, formerly of UGA and now with Beth Israel Deconess Medical Center at the Harvard Medical School.

Researchers actually discovered Hirano bodies decades ago but studying them in the lab proved so difficult that all the medical community could say was that the bodies were in some way associated with diseases such as Alzheimer’s. It was clear that Hirano bodies are composed primarily of filaments of actin, a protein that participates in many important cellular processes. But no one understood their function.

Fechheimer’s lab has been at the center of research on Hirano bodies for nearly a decade. In 2002, it reported for the first time a method of inducing the bodies to form. Interestingly, these “inclusions” also show up in autopsies of people suffering from diabetes, alcoholism and cancer. Hirano bodies also are associated with normal aging. So understanding what they do when neurological processes go off the rails could add an important step in understanding how diseases that cause so much suffering progress.

In a companion paper to the new mouse model research, published this year in the journal Neurobiology of Aging, Fechheimer and his co-authors discovered that Hirano bodies may actually act as a “corral” into which more damaging cellular molecules are “rounded up,” thus actually promoting cell survival and possibly even slowing the impact of disease. The idea that Hirano bodies may actually help protect cells from such disorders as Alzheimer’s came as a surprise to the team, though much research remains to be done to make sure exactly what is happening.

Co-authors on the paper in Neurobiology of Aging were Furukawa and Ha.

“The new results show us that Hirano bodies reduce cell death in a model system in a culture dish,” said Fechheimer. “Now we need to know if Hirano bodies have any harmful or protective effects on cells in the brain in a mouse and in human patients. We developed the new mouse model to begin to answer this question.”

The new model system will allow Fechheimer and his colleagues to study the impact of Hirano bodies in a living, mammalian system and to investigate the pathways for formation and degradation of the bodies. It will also allow them to test whether Hirano bodies promote or modulate the development of pathology or affect the deterioration of learning and memory that characterize both the human disease and the mouse models of these conditions.

The study, which is published in the cancer journal, Annals of Oncology today [1], was carried out in patients with non-small-cell lung cancer, but already the researchers are using it in a range of other cancers as well.

Patients with non-small-cell lung cancer (NSCLC) may have mutations in any of at least 14 different genes (probably more, as yet undiscovered). Until now, it has only been possible to search for single or a small number of genetic mutations. But as more and more genes are discovered to be involved in more cancers, it has become increasingly important to develop a way of determining the mutational status of a large number of genes at once.

Assistant Professor of Medicine at Harvard Medical School and thoracic medical oncologist at the Massachusetts General Hospital Cancer Center (Boston, USA), Lecia Sequist (MD, MPH), and Dora Dias-Santagata (PhD), who is co-director of the Translational Research Laboratory in the Massachusetts General Hospital Pathology Department and Instructor of Pathology at Harvard Medical School, and their team have developed a clinical test called SNaPshot. It can test over 50 well-known mutation sites (hot-spots) in 14 key cancer genes, with an average turnaround time from a sample being sent for testing to final results of just 2.8 weeks. The genes include those such as EGFR, KRAS, BRAF, HER2, etc.

SNaPshot uses a technique called “multiplex PCR”, which amplifies multiple mutation sites in different genes, in a single polymerase chain reaction (PCR) experiment [2], thereby saving considerable time and effort.

Dr Dias-Santagata explained: “This test allows us to look for a defined set of common mutations that occur in cancer cells, but not in the other cells of the body. These mutations affect genes that disrupt the checks and balances that usually govern the behaviour of normal cells, giving the mutant cells an advantage to divide and multiply, and the potential to give rise to a tumour. Targeted cancer therapies or ‘smart drugs’, each developed to fight a specific group of genetic aberrations, are now available. Because each tumour will harbour a specific set of mutations, the SNaPshot test allows us to match individual patients with the therapies that will most likely be effective in treating their cancer.” Dr Sequist added: “Choosing the right therapy can raise response rates in NSCLC patients from around 20-30% to 60-75% and may improve survival.”

From March 2009 to May 2010 samples from 589 NSCLC patients were analysed using SNaPshot; 546 patients had samples with enough tissue to be tested, and turnaround time ranged from 1 to 8.9 weeks – with the longer time usually being due to retesting some samples. One or more mutations or rearrangements were found in 51% (282) of the samples, with the most common being in the KRAS (24%), EGFR (13%), ALK (5%), TP53 (5%) and PIK3CA (4%) genes.

Out of 353 patients with advanced disease (stage IIIb, IV or recurrent), 170 had genetic mutations or rearrangements in EGFR, KRAS, ALK, BRAF, PIK3CA and HER2 genes and were classified as “potentially targetable” as these patients could join clinical trials examining drugs targeting these genetic changes. Another 30 patients with EGFR mutations were treated outside a clinical trial with erlotinib, an EGFR inhibitor, which is already used to treat lung cancer patients.

Prof Sequist said: “To our knowledge we are the first centre to offer this broad multiplexed genetic screening to all non-small-cell lung cancer patients. Broad genotyping is going to become part of everyday care for lung cancer patients – the field is clearly moving in this direction. Our study is exciting because it demonstrates that indeed it is possible today to integrate testing for multiple genetic biomarkers into a busy clinic and steer patients toward personalised therapies.”

Dr. Dias-Santagata added: “In contrast with prior genotyping strategies (mainly focused on testing EGFR and KRAS), employing a broad gene panel enabled us to provide a therapeutic alternative to lung cancer patients whose tumours harboured much less frequent genetic abnormalities (such as mutations in PIK3CA and BRAF, or rearrangements in ALK). Taken together, these individuals accounted for around ten percent of our patient population, but they would have remained ‘invisible’ in the absence of a comprehensive genotyping panel, like the one used here.”

Prof Sequist and Dr Dias-Santagata say that SNaPshot can be performed in most existing clinical molecular diagnostic laboratories affiliated to hospitals and other institutions, using equipment that is already available.

Although SNaPshot was used initially on NSCLC patients, Dr Dias-Santagata and her colleagues are now using it in a range of solid tumours such as colorectal, breast and gliomas. In addition, they are planning to extend their analyses to cancers of the blood, including acute myeloid leukaemia. “While the present report describes the results of lung cancer genotyping, the SNaPshot test has been making a difference to clinical decision-making for a broader range of cancer patients. Future goals for testing involve the use of several technologies to obtain a more detailed genetic signature for each tumour. We hope that this approach will help us identify therapeutic options for a much larger fraction of cancer patients and provide a good resource to understand differences in response to therapy,” said Dr Dias-Santagata.

The study is the first to outline how to limit and repair DNA damage defects in cells and could provide a model for understanding processes that cause us to age.

The findings could have significant benefits, such as reducing degeneration of some tissues in older age, and could assist health management in countries, including the UK, where average life expectancy is extending, according to the researchers.

The first results of the 18-month study, led by Durham University, are published in the journal Human Molecular Genetics.

Researchers looked at a group of inherited degenerative disorders called Laminopathies that are caused by mutations in the gene LMNA. The most severe disorders linked to mutation in this gene include Hutchinson Gilford Progeria Syndrome (HGPS), a fatal disease that causes premature ageing in children.

The Durham University and University of Bologna team used in-vitro models and molecular imaging techniques to measure levels of oxidative stress and DNA damage in cells. Oxidative stress relates to the dynamics of cells and the body’s ability to detoxify and repair itself. When cells are stressed, levels of highly reactive molecules known as reactive oxygen species (ROS) can increase dramatically. This can result in significant damage to cell structures and to DNA which is one underlying cause of premature ageing and standard ageing.

The team monitored changes in thousands of ‘crinkly’, damaged cells after administering NAC, a widely-used and well-tolerated drug. They found that while this drug did not affect some aspects of cell stress that are effectively controlled by currently used drugs, it very effectively controlled ROS generation and DNA damage. The results suggest that administration of NAC in combination with currently used drugs might improve the health of children with progeria.

Professor Chris Hutchison, a member of the Biophysical Sciences Institute, Durham University, said: “In children with progeria, we can see that double-strand breaks in the DNA architecture of cells increase which in turn adds to poor rates of cell growth. Our treatment of these cells with the drug N-acetyl cysteine (NAC) reversed both of these effects.

“Mutations in the LMNA gene cause more diseases, such as muscular dystrophy, than any other that we know. We’ve found that DNA damage can be controlled and our findings could be an important step to helping both children with progeria and older people to live lives that are less debilitating in terms of health problems.”

The researchers said their findings were at an early stage and further studies and human clinical trials would be needed to develop effective drug treatments.

Professor Hutchison added: “We are using a careful approach that will look at patients with progeria to see if there’s a model that can be used for wider medicine. It would be great to find a way to help relieve some of the effects of progeria and to extend the children’s lives, whilst also finding a way to help increasingly ageing populations in many parts of the world.

“The findings are at a very early stage but they show the potential for helping people to live more comfortable and less painful lives when they reach 70 and 80 years of age and beyond.”

Hutchinson-Gilford Progeria Syndrome “Progeria” or “HGPS” is a rare, fatal genetic condition characterized by an appearance of accelerated aging in children. Progeria has a reported incidence of about 1 in 4 – 8 million newborns from all over the world. It affects both sexes equally and all races. Although they are born looking healthy, children with Progeria begin to display many characteristics of accelerated aging at around 18-24 months of age.

Progeria signs include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular (heart) disease and stroke. The children have a remarkably similar appearance, despite differing ethnic backgrounds. Children with Progeria die of atherosclerosis (heart disease) at an average age of thirteen years (with a range of about 8 – 21 years).

Dr. Leslie Gordon, Medical Director for The Progeria Research Foundation, said: “Dr. Hutchison’s study has not only confirmed basic cellular defects in Progeria, but has also identified potential ways to improve those defects. This type of biological science is how progress towards treatments and a cure for children with Progeria will advance.”

The research could also provide a model for the future for tailoring treatments and dosages of drugs to the individual and therefore improving patient health where drugs are administered.

Ivacaftor, also known as VX-770, was developed by Vertex Pharmaceuticals with financial support from the Cystic Fibrosis Foundation. The oral medicine targets the defective protein produced by the gene mutation called G551D that causes CF. Researchers found that patients carrying G551D – approximately four per cent of all CF patients – who were treated with VX-770 showed a 17 per cent relative improvement in lung function that was sustained over the course of 48 weeks.

Additionally, patients with G551D treated with VX-770 showed improvements in other areas critically important to the health of people with CF. Study participants experienced significant reductions in sweat chloride levels indicating an improvement in the body’s ability to carry salt in and out of cells – a process which when defective leads to CF. They also experienced decreased respiratory distress symptoms and improved weight gain. Those who received VX-770 gained on average seven pounds compared to those in the placebo group who gained approximately one pound. This is significant because many people with CF have difficulty gaining and maintaining weight due to reduced lung function and chronic infection.

“Our study shows that we are now able to improve the quality of life for cystic fibrosis patients with the G551D mutation with the administration of VX-770,” said Dr. Ramsey, director of the Center for Clinical and Translational Research at Seattle Children’s Research Institute and endowed chair in Cystic Fibrosis (CF) in the Department of Pediatrics at the University of Washington School of Medicine.

Dr. Ramsey and co-investigators evaluated lung function in patients 12 years or older who carry at least one copy of the G551D mutation. The study included 161 patients at multiple healthcare centers who received at least one dose of VX-770 or placebo. The study is the third and final in a series designed to assess VX-770′s effectiveness and safety before it is approved for public use.

Approximately 30,000 children and adults in the United States and 70,000 people worldwide have CF. The disease is caused by a defective gene that affects many parts of the body, but is especially harmful to the lungs and pancreas. The gene mutation causes very thick, sticky mucus to clog the lungs and often cause life-threatening infections. In the 1950s, few children with CF lived beyond age five. Today, advances in research and medical treatments have made it possible for people with CF to live well into their 30s, 40s and beyond.

“Overdoses involving prescription painkillers are at epidemic levels and now kill more Americans than heroin and cocaine combined, ” said CDC Director Thomas Frieden, M.D., M.P.H. “States, health insurers, health care providers and individuals have critical roles to play in the national effort to stop this epidemic of overdoses while we protect patients who need prescriptions to control pain. ”

The increased use of prescription painkillers for nonmedical reasons (without a prescription for the high they cause), along with growing sales, has contributed to the large number of overdoses and deaths. In 2010, 1 in every 20 people in the United States age 12 and older—a total of 12 million people—reported using prescription painkillers nonmedically according to the National Survey on Drug Use and Health. Based on the data from the Drug Enforcement Administration, sales of these drugs to pharmacies and health care providers have increased by more than 300 percent since 1999.

“Prescription drug abuse is a silent epidemic that is stealing thousands of lives and tearing apart communities and families across America, ” said Gil Kerlikowske, Director of National Drug Control Policy.  “From day one, we have been laser–focused on this crisis by taking a comprehensive public health and public safety approach.  All of us have a role to play. Health care providers and patients should be educated on the risks of prescription painkillers. And parents and grandparents can take time today to properly dispose of any unneeded or expired medications from the home and to talk to their kids about the misuse and abuse of prescription drugs. ”

In April, the Administration released a comprehensive action plan to address the national prescription drug abuse epidemic to reduce this public health burden.

Titled “Epidemic: Responding to America’s Prescription Drug Abuse Crisis, ” the plan includes support for the expansion of state–based prescription drug monitoring programs, more convenient and environmentally responsible disposal methods to remove unused medications from the home, education for patients and healthcare providers, and support for law enforcement efforts that reduce the prevalence of “pill mills” and doctor shopping.   

Already, 48 states have implemented state–based monitoring programs designed to reduce diversion and doctor shopping while protecting patient privacy and the Department of Justice has conducted a series of takedowns of rogue pain clinics operating as “pill mills. ”  President Obama has also signed into law the Secure and Responsible Drug Disposal Act, which will allow states and local communities to collect and safely dispose of unwanted prescription drugs and support DEA’s ongoing national efforts to collect unneeded or expired prescription drugs  which have collected over 300 tons of medications over the past year.

  “Almost 5,500 people start to misuse prescription painkillers every day, ” said Substance Abuse and Mental Health Services Administration Administrator Pamela S. Hyde.  “Just like other public health epidemics, community–based prevention can be a proven, life–saving and cost–effective key to breaking the trend and restoring health and well–being. ”

The prescription painkiller death rates among non–Hispanic whites and American Indians/Alaska Natives were three times those of blacks and Hispanic whites. In addition, the death rate was highest among persons aged 35–54 years. Overdose resulted in 830,652 years of potential life lost before age 65 years, a number comparable to the years of potential life lost from motor vehicle crashes and much higher than the years of potential life lost due to homicide.

For the analysis, CDC reviewed state data on fatal drug overdoses, nonmedical use of prescription painkillers, and sales of prescription painkillers to pharmacies and health care providers.

The study found:

• State death rates from overdoses (from 2008 data) ranged from a high of 27.0 deaths per 100,000 people in New Mexico to a low of 5.5 deaths per 100,000 people in Nebraska.
• Nonmedical use of prescription painkillers ranged from a high of 1 in 12 people aged 12 and older in Oklahoma to a low of 1 in 30 in Nebraska. States with more nonmedical use tend to have more deaths from drug overdoses.
• Prescription painkiller sales per person were more than three times higher in the highest state, Florida, than in the lowest state, Illinois. States with higher sales per person tend to have higher death rates from drug overdose.

While national strategies are being strengthened, states, as regulators of health care practice and large public insurers, can take the following steps to help prevent overdoses from prescription painkillers and reduce this public health burden:

• Start or improve prescription drug monitoring programs, which are electronic databases that track all prescriptions for painkillers in the state.
• Use prescription drug monitoring programs, public insurance programs, and workers’ compensation data to identify improper prescribing of painkillers.
• Set up programs for public insurance programs, workers’ compensation programs, and state–run health plans that identify and address improper patient use of painkillers.
• Pass, enforce and evaluate pill mill, doctor shopping and other state laws to reduce prescription painkiller abuse.
• Encourage professional state licensing boards to take action against inappropriate prescribing.
• Increase access to substance abuse treatment.

CDC is also releasing “Policy Impact: Prescription Painkiller Overdoses, ”one in a series of issue briefs highlighting key public health issues and important, science–based policy actions that can be taken to address them. Through this new publication, CDC supports state–based efforts to reduce prescription drug abuse while ensuring patients have access to safe, effective pain treatment.

Moreover, almost all of these co-infected children were rapidly treated with vancomycin, considered to be appropriate treatment for MRSA. The fact that they died despite this treatment is especially alarming given the rising rates of MRSA carriage among children in the community.

“There’s more risk for MRSA to become invasive in the presence of flu or other viruses,” says study leader Adrienne Randolph, MD, MsC, of the Division of Critical Care Medicine at Children’s Hospital Boston. “These deaths in co-infected children are a warning sign.”

The researchers hope their findings, published Nov. 7 by the journal Pediatrics, (eFirst pages) will promote flu vaccination among all children aged 6 months and older. (No flu vaccine is currently available for children younger than 6 months.)

“The 2009 H1N1 virus has not changed significantly to date,” notes Tim Uyeki, MD, MPH, of the Influenza Division of the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC), a senior investigator on the study. “Infections of children in the U.S. with 2009 H1N1 virus are expected this season and need to be prevented and treated appropriately. Influenza vaccination protects against 2009 H1N1 illness.”

With emergency funding from the National Institutes of Health, Randolph and her colleagues in the Pediatric Acute Lung Injury and Sepsis Investigator’s Network tracked 838 children admitted to 35 pediatric ICUs around the country with probable 2009 H1N1 influenza from April 2009 to April 2010. Their vaccination status wasn’t consistently known, but H1N1 vaccine did not become available until September 2009 or later.

The median age of the children critically ill with H1N1 was 6 years. Most had respiratory failure, two thirds required mechanical ventilation, and some required extracorporeal membrane oxygenation (ECMO) for advanced cardiac and respiratory support. Their disease progressed rapidly, and 75 children (9 percent) died, two thirds of them within two weeks of ICU admission.

“Some children were quickly overwhelmed, and many died despite centers doing everything to save them,” says Randolph. “Early in the pandemic, centers were worried that they would run out of ventilators, that they would run out of ICU beds.”

While most of the children critically ill with H1N1 had one or more chronic health conditions that increased their risk, such as asthma, neurologic disorders or compromised immune systems, 251 children (30 percent) were previously healthy.

Among these otherwise healthy children, the only risk factor that was identified for death from influenza was a presumed diagnosis of MRSA co-infection in the lung – which increased the risk for mortality 8-fold (P<0.0001).

“It is not common in the U.S. to lose a previously healthy child to pneumonia,” says Randolph. “Unfortunately, these children had necrotizing pneumonia – eating away at their tissue and killing off whole areas of the lung. They looked like immunocompromised patients in the way MRSA went through their body. It’s not that flu alone can’t kill – it can – but in most cases children with flu alone survived.”

Treatment challenges

Use of antiviral agents for critically ill patients with influenza is now routinely recommended. In this study, 88 percent of the children admitted to the ICU received Tamiflu (oseltamivir) during their stay, but only 6 percent had received it prior to hospital admission. Randolph believes it’s possible that earlier antiviral treatment might have saved some of these children, especially those who died of influenza without bacterial co-infection. (Influenza antiviral medications work best when given within the first two days of symptom onset.)

The study also found that most of the MRSA co-infected children who died had received vancomycin promptly at or before ICU admission. The researchers aren’t sure why this antibiotic of choice didn’t save these children – perhaps it couldn’t penetrate the lung, or perhaps the disease moved too rapidly.

Physicians seeing children with serious lower-respiratory-tract disease during flu season are urged to give early antiviral treatment (Tamiflu or zanamivir [Relenza]) and antibiotics covering MRSA and other flu-associated bacteria, even before suspected infections are confirmed in the lab, the researchers say.

But other approaches are urgently needed. “MRSA is hard to develop a vaccine against – researchers have been trying since the 1960s and have been unsuccessful,” says Randolph. “So the only way to prevent these severe complications is to get everyone vaccinated against the flu, and do more studies of MRSA colonization so we can prevent it in the community and in kids.”

A growing threat

Recent studies point to a rise in the number of children carrying MRSA. A study in Pediatrics in 2010 found that the number of children hospitalized for MRSA infection increased from 2 in 1,000 admissions in 1999 to 21 in 1,000 admissions in 2008. This rise was attributed mostly to community-acquired cases – not cases acquired in the hospital.

Many observers attribute the rise to increased use of antibiotics in both people and animals. “The more antibiotics we take, the more we colonize ourselves with antibiotic-resistant organisms such as MRSA,” says Randolph.

Influenza appears to suppress the immune response, making children who are already colonized more susceptible to invasive bacterial disease. “Previously, MRSA has not been considered a common cause of pneumonia in kids but this may be changing,” Randolph says. “It’s likely that flu and other viral infections let MRSA invade and that there’s some synergistic reaction between flu and these bacteria.”

While recent data show an increase in MRSA co-infection in children dying from seasonal influenza, this is the first study to collect data on a large number of children with no risk factors for severe flu.

Dr. Yancy, who will deliver the Heart and Stroke Foundation of Canada Lecture at the opening ceremonies of the Canadian Cardiovascular Congress in Vancouver this Sunday, will tell delegates that people who follow seven simple steps to a healthy life can expect to live an additional 40 to 50 years after the age of 50.

“Achieving these seven simple lifestyle factors gives people a 90 per cent chance of living to the age of 90 or 100, free of not only heart disease and stroke but from a number of other chronic illnesses including cancer,” says Dr. Yancy, a professor of medicine and chief of cardiology at the Northwestern University’s Feinberg School of Medicine. He is also the past-president of the American Heart Association.

“By following these steps, we can compress life-threatening disease into the final stages of life and maintain quality of life for the longest possible time.” He predicts that, if we act now, we can reverse the tide by 2020.

According to the Heart and Stroke Foundation, every year in Canada about 250,000 potential years of life are lost due to heart disease and stroke, which are two of the three leading causes of death in Canada.

Canadians can achieve optimal health, says Dr. Yancy, by following these steps:

GET ACTIVE: Inactivity can shave almost four years off a person’s expected lifespan. People who are physically inactive are twice as likely to be at risk for heart disease or stroke.
KNOW AND CONTROL CHOLESTEROL LEVELS: Almost 40 per cent of Canadian adults have high blood cholesterol, which can lead to the build up of fatty deposits in your arteries − increasing your risk for heart disease and stroke.

FOLLOW A HEALTHY DIET: Healthy eating is one of the most important things you can do to improve your health – yet about half of Canadians don’t meet the healthy eating recommendations.
KNOW AND CONTROL BLOOD PRESSURE: High blood pressure − often called a ‘silent killer’ because it has no warning signs or symptoms − affects one in five Canadians. By knowing and controlling your blood pressure, you can cut your risk of stroke by up to 40 per cent and the risk of heart attack by up to 25 per cent.
ACHIEVE AND MAINTAIN A HEALTHY WEIGHT: Almost 60 per cent of Canadian adults are either overweight or obese − major risk factors for heart disease and stroke. Being obese can reduce your life span by almost four years.

MANAGE DIABETES: By 2016 an estimated 2.4 million Canadians will live with diabetes. Diabetes increases the risk of high blood pressure, atherosclerosis (narrowing of the arteries), coronary artery disease, and stroke, particularly if your blood sugar levels are poorly controlled.
BE TOBACCO FREE: More than 37,000 Canadians die prematurely each year due to tobacco use, and thousands of non-smokers die each year from exposure to second-hand smoke. As soon as you become smoke-free, your risk of heart disease and stroke begins to decrease. After 15 years ,your risk will be nearly that of a non-smoker.
A call for focused prevention strategies

While this goal of optimal health has been achieved by fewer than 10 per cent of the population, “it demonstrates the striking potential that prevention has if it is broadly embraced,” says Dr. Yancy. “We know how to prevent heart disease and stroke – we now need to build the tools to empower our citizens to manage their risk and prevent heart disease.”

Dr. Yancy calls on governments to invest in steady and focused prevention strategies. He says that necessary initiatives include a change in current sodium policies, continued progress in tobacco control initiatives, increased green space, and health education.

“Healthy living is key to preventing heart disease and stroke,” says Bobbe Wood, president of the Heart and Stroke Foundation of Canada. “The Foundation is committed to raising awareness about heart health and to promoting public policies that facilitate healthy lifestyles and communities.”

She says that the Foundation will continue to build on partnerships and policies that have led to a significant reduction of trans fats in the Canadian food supply; stronger tobacco control initiatives; healthy community design; and a continued reduction in the amount of salt in our food products, which has been achieved in part through Health Check™, the Foundation’s flagship food information program.

Dr. Yancy adds that improved access to health care that focuses on prevention and control of important risk factors including high blood pressure, high cholesterol and diabetes is also key.

Raising the alarm over looming costs of treating heart disease

Dr. Yancy will also raise the alarm over the looming cost of treating heart disease now and in the future. With predictions that the direct medical cost of treating heart disease in the U.S. alone could climb to $818 billion in 2030, he says there is a health and economic imperative for governments and societies around the world to embrace prevention strategies.

Heart disease and stroke cost the Canadian economy more than $20.9 billion every year in physician services, hospital costs, lost wages and decreased productivity.

“The opportunity for prevention is not an unrealistic expectation,” says Dr. Yancy. “Over the past 40 years the rates of heart disease and stroke have steadily declined.” The rate has declined in Canada by 70 per cent since the mid-1950s. In the last decade alone, the rate has declined by 25 per cent.

Unfortunately, says Dr. Yancy, these benefits may be short-lived if the burden of risk, specifically obesity and diabetes, continues to grow, especially in children. “We need to act now.”

We offer several different treatments for eliminating acne blemishes, but the real secret to smooth, clear skin is finding a customized skin care regimen that is tailored to your skin’s specific needs. Everyone’s skin is different and our job is to help you design a plan that will get your skin acne free and put an end to the frustrations of going through dozens of products without achieving any results.

To better understand why Acne can be as persistent and frustrating as it is, let’s take a closer look at what Acne is and it’s possible causes…

Read full article via Acne Treatment Arlington

A year after the 35 patients in the study had Roux-en-Y gastric bypass surgery, their obese adult family members weighed on average 8 pounds less, the researchers say.

In addition, many of the children in these families also appeared to benefit through their close association with the patient, exhibiting a lower body mass index than would have been expected given their growth curve.

The study notes that overweight women on a traditional medically supervised diet, such as Atkins or Ornish, lose between 2 and 5 percent of their body weight over 12 months. Over that same period of time, both obese men and women in the families of the surgery patients lost 3 percent of their body weight overall — slimming down, on average, from 234 to 226 pounds.

“Family members were able to lose weight comparable to being part of a medically controlled diet simply by accompanying the bariatric surgery patient to their pre- and post-operative visits,” said senior author John Morton, MD, MPH, associate professor of surgery at Stanford and director of bariatric surgery at Stanford Hospital & Clinics.

The findings will be published Oct. 17 in the Archives of Surgery. The lead author of the study is Gavitt Woodard, MD, a 2011 graduate of the Stanford School of Medicine.

The 50 adults and children who participated in the study did more than just share a house with the bariatric patients; they also, as Morton noted, accompanied the patients to all of their pre- and post-operative clinical visits, where they received dietary and lifestyle counseling. These sessions would emphasize a high-protein, high-fiber, low-fat and low-sugar diet and small, frequent meals. The sessions also set daily goals for exercise and stressed a good night’s sleep, alcohol moderation and less time in front of the television.

After a year, not only did obese adult family members lose several pounds, but their waistlines also decreased on average from 47 inches to 44 inches. Weight loss among non-obese family members, however, was not significant (180 to 176 pounds), and their waist circumference held steady at an average of 39 inches. But the number of alcoholic drinks consumed by the adult family members, regardless of weight, decreased sharply, from 11.4 to 0.8 each month.

In addition, the mean body mass index among obese children in the study was lower than what would have been expected based on projected growth-curve metrics from the Centers for Disease Control and Prevention.

Adult family members made significant changes in their eating habits, with less emotional and uncontrollable eating. Both adults and children made substantial increases in their activity levels. For adult family members, metabolic equivalent task hours, a measure of physical-energy expenditure, more than doubled from 7.8 to 16.8; for children, the increase was from 12.9 to 22.4.

When behavior changes as a result of social-reinforcing conditions, it is sometimes known as a halo effect. For example, studies have found that people are more likely to quit smoking if their spouses quit, or become obese if a friend becomes obese.

Today, 26 percent of American adults and 15 percent of children are considered obese, which increases the risk of mortality related to diabetes, heart disease and cancer, the study says.

Morton noted that Stanford surgeons perform about 300 bariatric surgeries every year, and more than 200,000 are done annually in the United States.

“Can you imagine if every one of these bariatric patients were an ambassador for good health? You would have a huge, grassroots movement with bariatric surgery providing a vehicle for healthy change for patient and family alike,” Morton said. “Obesity is a family disease and bariatric surgery sets the table for future, healthy family meals.”

The authors conclude by saying, “Bariatric surgery programs should encourage family involvement in support groups and education sessions to capitalize on these halo effects.”

The success of this vaccine, CSIC’s patent, is based on the capability of human’s immune system to learn how to react over time against virus particles and infected cells. “MVA-B vaccine has proven to be as powerful as any other vaccine currently being studied, or even more”, says Mariano Esteban, head researcher from CSIC’s National Biotech Centre.

In 2008, MVA-B already showed very high efficiency in mice as well as macaque monkeys against Simian’s immunodeficiency virus (SIV). Due to it’s high immunological response in humans, Phase I clinic trials will be conducted with HIV infected volunteers, to test its efficiency as a therapeutic vaccine.

Weapon’s origins

Back in 1999, Esteban’s research team began to work in the development and preclinical studies of MVA-B, which name comes from its composition, based in Modified Ankara Vaccinia virus. MVA-B is an attenuated virus, which has already been used in the past to eradicate smallpox, and also as a model in the research of many other vaccines. The “B” stands for the HIV subtype it is meant to work against, the most common in Europe.

Development of MVA-B is based in the insertion of four HIV genes (Gag, Pol, Nef & Env) in Vaccina’s genetic sequence. A healthy immunitary system is able to react against MVA.

On the other hand, the inserted HIV genes in its DNA are not able to self-replicate, which guarantees the safety of the clinical trial.

30 healthy volunteers participated in this clinical trial. 24 of them were treated with MVA-B, while the other 6 were treated with a placebo, following a double-blind testing method. 3 doses of the vaccine were given via intramuscular route in weeks 0, 4 and 16. The effects were studied in peripheral blood until the trial ended on week 48.

Combat battalion

Inoculating the vaccine in a healthy volunteer is intended to train it’s immune system to detect and learn how to combat those virus components. According to Esteban ” it is like showing a picture of the HIV so that it is able to recognise it if it sees it again in the future”.

Lymphocytes T and B are the main cells in this experiment, the soldiers in charge of detecting the foreign substances in the body and sending the right coordinates to destroy them.

“Our body is full of lymphocytes, each of them programmed to fight against a different pathogen” says Esteban. For that reason “Training is needed when it involves a pathogen, like the HIV one, which cannot be naturally defeated”.

Lymphocytes B are responsible for the humoral immune response, producing antibodies which attack the HIV particles before they penetrate and infect the cell, anchoring themselves to the external structure and blocking it. 48th week blood tests reveal 72,7% of the treated volunteers hold specific antibodies against HIV.

On the other side, lymphocytes T control cell’s immune response, in charge of detecting and destroying HIV infected cells. In order to verify their defence response to the vaccine, production of interferon gamma immunitary protein was measured.

Tests performed on the 48th week, 32 weeks after the last inoculation of the vaccine, show the production of lymphocytes T CD4+ and CD8+ of the vaccinated group is 38,5% and 69,2%, respectively, while it stays at 0% in the control group.

Action in several fronts

Besides interferon gamma, other immune proteins (cytokines and chemokines) are produced by the body when the presence of a pathogen is detected. Each of these proteins tends to attack a different enemy front. When T lymphocytes’ defence action is able to generate several of these proteins it is called a polyfunctional action. CSIC’s researcher adds “The importance of polyfunctionality has to do with the capability of pathogens to develop resistance to the immune systems attacks. The higher the polyfunctionality, the lower the resistance”.

The defence spectrum of T lymphocytes in vaccinated subjects was measured based on the production of 3 other immunitary proteins. Tests indicate the vaccine generates up to 15 types of lymphocyte T CD4+ and CD8+ populations. 25% of CD4+ type and 45% of CD8+ type are able to produce two or more different proteins, proving their polyfunctionality.

War veterans

For a vaccine to become really effective, besides its immune system’s defence capability, generating a long lasting response against future attacks is the key. For this purpose, the body needs to be able to keep a basic level of memory T lymphocytes. These lymphocytes, generated after a first pathogen attack, are veteran soldiers, which can circulate the body for years, prepared to respond to a new enemy’s incursion.

48th week blood tests ran on vaccinated subjects show over 50% of CD4+ and CD8+ lymphocytes were memory T lymphocytes in the 85% of the patients who kept an immune response at this point of the trials.

In Esteban’s opinión “MVA-B immune profile meets, initially, the requirements for a promising HIV vaccine”. MVA-B is not capable of removing the virus from the body as once a cell is infected, virus’ genetic data is integrated and replicated with the cell. However, the immune response induced by the vaccine could keep the virus under control, “if the virus enters the body and tries to develop in a cell, the immune system is ready to inactivate the virus and destroy the infected cell”.

According to CSIC’s researcher: “If this genetic cocktail passes Phase II and Phase III future clinic trials, and makes it into production, in the future HIV could be compared to herpes virus nowadays”. Virus would not cause a disease anymore and would become a minor chronic infection, which would only show its effects in a low defence scenario, with a much lower contagious profile.

"It's important for children with autism to begin treatment as soon as possible, " said Micah Mazurek, assistant professor in the University of Missouri School of Health Professions

“It’s important for children with autism to begin treatment as soon as possible,” said Micah Mazurek, assistant professor in the School of Health Professions and the Thompson Center for Autism and Neurodevelopmental Disorders. “The more intense or comprehensive the therapy, the better it is in terms of helping children improve social and communication skills.”

Data was collected from more than 1,000 children and adolescents with ASD. The researchers measured fifteen social-communication skills, including facial expressions, gestures, language comprehension, sharing enjoyment and appropriate social responses. When examining change over time in these skills, the majority (95.4 percent) demonstrated improvement.

Those who received therapy, including behavioral, speech, and occupational therapy, had the best outcomes. The response to therapy was greatest among those with higher nonverbal IQs. Controlling for age and symptom severity, children who received more intensive treatment at younger ages experienced greater advancements in social-communication symptoms.

“With regard to social-communicative symptom severity, our study reveals that it is not IQ alone that contributes to improvements over time,” Mazurek said. “Instead, having a higher IQ may allow children to make greater gains in various types of treatments. Although IQ scores of children with ASD may be strongly influenced by their capacity for attention and ability to comply with tasks results indicate the need to design and examine alternative treatment approaches for those with intellectual impairments.”

For those children who were nonverbal at age 5, the researchers found that IQ and intensity of speech therapy most significantly predicted the acquisition of speech. The findings indicate that targeted, intensive treatments may be most successful in improving specific skills.

Mazurek is an assistant professor in the Department of Health Psychology. The study, “Predicting improvement in social-communication symptoms of autism spectrum disorders using retrospective treatment data,” will be published in Research in Autism Spectrum Disorders. The research was funded by a grant from the Simons Foundation, a private foundation based in New York City that supports research to improve the diagnosis and treatment of autism spectrum disorders.

The mice suffered fewer side effects compared with traditional cancer treatment relying on heavy doses that can cause hair and bone loss.While chemotherapy given repeatedly in small portions, called metronomic dosing, is not new, the studys authors say that the dosing appears to alter the cellular activity of the drug topotecan. This finding offers promising new ways to use topotecan — which is widely used and approved by the Food and Drug Administration for cervical and other cancers—to combat slowly growing prostate tumors. The findings appear this month in the journal Cancer Biology and Therapy.

“At these lower doses, there isnt enough topotecan to follow a classic cell death pathway,” said study co-author Robert D. Arnold, a Georgia Cancer Coalition Distinguished Scholar and assistant professor in the UGA College of Pharmacy. “Our research suggests that metronomic dosing altered topotecans behavior.”Scientists have known that topotecan given to patients in large, traditional doses kills cancer cells by deactivating proteins known as enzymes that are necessary for cell growth, Arnold explained.

By contrast, metronomic dosing of topotecan prevents new blood vessels — which are necessary for growth — from forming in the tumor. Arnold and his colleagues discovered that topotecan did not change the amount of blood vessels formed, but significantly decreased tumor size and altered genes critical for controlling cell growth.Brian S. Cummings, a co-author and associate professor at the pharmacy college, compared topotecans process of killing tumor cells to the everyday task of running an errand.”Lets assume youre going to go to the grocery store and you could walk, ride your bike or take the car,” he said.

“Those are different mechanisms of action. You will still get to the same place.”He added that researchers try to determine which pathway, or transportation choice, cells take after different amounts of exposure to topotecan. Their results suggest that when topotecan is given frequently in low doses, the drug could be changing the type of genes turned on in the tumor. These changes may be related to the structure or architecture of a gene — not a change in gene sequence. Such changes could be considered epigenetic, but more research is needed, Arnold said. IMAGE: University of Georgia researcher Robert Arnold has found that smaller, less toxic amounts of chemotherapy medicine given frequently to mice with human prostate cancer noticeably slowed tumor growth.Click here for more information.

The study suggests that metronomic dosing of topotecan can reduce prostate cancer growth at drug concentrations far below those that can be toxic to healthy cells in the body.Given the limited treatment options for late-stage prostate cancer and clinical use of topotecan, new clinical trials could occur in the near future, Arnold said. The same research team is now studying the dosing effects of topotecan in breast cancer models.

An international consortium of 175 scientists from 126 centres in Europe, the USA and Australia identified genetic variants associated with the health of the human lung. Their discovery sheds new light on the molecular basis of lung diseases like Chronic Obstructive Pulmonary Disease (COPD).

It is the first time that these sixteen common genetic variants have been definitely linked with lung function. Researchers say the new pathways discovered could be targeted by drugs.

The study was led by Professor Martin Tobin from the University of Leicester, and Professor Ian Hall from The University of Nottingham and Dr Stephanie London from the U.S. National Institute of Environmental Health Sciences.

The pioneering research involved a genetic study of 2.5 million genetic variants in each of 48,201 people across the world. A smaller number of the most promising variants were then studied in a further 46,411 individuals. The research, part-funded by the UK Medical Research Council (MRC) and the Wellcome Trust, is published today in Nature Genetics.

The recent discoveries build on research published by the same authors last year, bringing the total number of genetic variants associated with lung function to twenty six. The same authors also showed, in research published in the American Journal of Respiratory and Critical Care Medicine in June 2011, that variants which predict lung function also predict the disease, COPD.

Professor Martin Tobin, Professor of Genetic Epidemiology and Public Health & MRC Senior Clinical Fellow at the University of Leicester, said: “COPD – a progressive disease that makes it hard for people to breathe – affects around 1 in 10 adults above the age of 40 and is fourth most common cause of death worldwide.

“Smoking is the most important risk for developing COPD. Smokers are not all equally likely to develop COPD and differences in susceptibility occur due to the genetic variants people carry. For the first time we understand what so many of these genetic variants are, including the underlying mechanisms that they point to. We now need to prioritise research to better understand these disease mechanisms and inform improved patient care.

“These discoveries could provide the key to new therapies for lung diseases such as COPD. It is too early to say whether this information would be of use as a screening test to predict the development of COPD. Stopping smoking is the best way to prevent COPD.

Professor Ian Hall said “This work is important because until recently we have not understood the factors which underlie inherited variability in lung function. The very large genetic studies required to identify key genes would not have been possible without the support of many groups around the world and the input of thousands of subjects. We now need to take the knowledge gained from this study to do two things: firstly to learn more about the function of genes which contribute to the risk of developing lung diseases such as COPD, and secondly to try and develop strategies to use genetic information to improve the clinical care provided to individual patients.”