Antibiotic Use Aids MRSA Spread in Hospital and Infection Control Measures Do Little to Prevent It, Says Hospital Study

The use of a commonly prescribed antibiotic is a major contributor to the spread of infection in hospitals by the 'superbug' MRSA, according to new research. The study also found that increasing measures to prevent infection -- such as improved hygiene and hand washing -- appeared to have only a small effect on reducing MRSA infection rates during the period studied.

MRSA -- methicillin-resistant Staphylococcus aureus -- is a bacteria that causes hospital-acquired infection and is resistant to all of the penicillin-type antibiotics frequently used in hospitals to prevent and treat infection. It can cause serious infections of the skin, blood, lungs and bones.

The researchers -- led by St George's, University of London -- tracked MRSA infection over 10 years from 1999 to 2009 at St George's Hospital, looking at how it has adapted to survive in a hospital environment and at factors that affected its prevalence. They found that a significant drop in MRSA rates coincided with a reduction in hospital prescriptions of ciprofloxacin, the most commonly prescribed antibiotic of the fluoroquinolone family.

Over a short period of the study, ciprofloxacin prescriptions fell from 70-100 daily doses for every thousand occupied beds to about 30 doses. In the same period, the number of patients identified by the laboratory to be infected with MRSA fell by half, from an average of about 120 a month to about 60. Following this, over the last two years of the study both the drug prescription level and MRSA rates remained at these reduced levels. Symptoms of MRSA infection can range from very mild to severe, but it is not known how many of the cases examined in the study were serious.

The study -- published in the Journal of Antimicrobial Chemotherapy -- looked at whether other factors such as improved infection control measures may have contributed to this decrease in infection. However, during a four-year period when more stringent infection control policies were introduced -- including improved cleaning and hand washing, and screening patients for MRSA on arrival at hospital -- the only major reduction in MRSA infection rates coincided with the reduction in ciprofloxacin prescriptions.

Lead author Dr Jodi Lindsay, a reader in microbial pathogenesis at St George's, University of London, said: "Surprisingly, it wasn't hygiene and hand washing that were the main factors responsible for the decrease in MRSA in the hospital. Rather, it seemed to be a change in the use of a particular group of antibiotics. Hand washing and infection control are important, but they were not enough to cause the decrease in MRSA we saw."

Dr Lindsay said the study suggested that MRSA relies on ciprofloxacin -- and fluoroquinolones in general -- to thrive in hospitals, as well as penicillin-type drugs, which was already assumed. The fluoroquinolone group of antibiotics have a similar enough mechanism of action to assume that the effect would be the same for them all.

She added that the findings suggest the most effective way to control MRSA and other hospital-based superbugs is to continue finding alternative ways to use antibiotics, rather than simply focusing on infection control techniques.

As well as identifying factors that influenced prevalence, the researchers identified the strain of MRSA that has become dominant. This strain -- CC22 -- has thrived by developing and maintaining multi-drug resistance, and becoming more fit to survive on hospital surfaces than other strains.

Dr Tim Planche, consultant microbiologist at St George's Healthcare NHS Trust and one of the co-authors of the study, said: "The Trust currently has infection rates among the lowest in London, having successfully driven acquisitions down over the past five or six years using a combination of both tough hygiene regimes and careful selective use of antibiotics. These findings, however, provide valuable insight and certainly warrant further investigation, which could lead to the development of even more effective infection control strategies in future."

Dr Lindsay said that studying the dynamic of how MRSA bacteria strains continue to evolve in hospitals in response to changing practice and interventions, such as infection control and antibiotic prescribing, will be essential to determine which interventions work, which are cost effective, and which are likely to have the best long-term outcomes.

She added: "But it seems that we now have an excellent opportunity to control superbugs in hospitals by re-examining how we prescribe antibiotics and ensuring we're using them in the most effective way possible."

Journal Reference:

1. G. M. Knight, E. L. Budd, L. Whitney, A. Thornley, H. Al-Ghusein, T. Planche, J. A. Lindsay. Shift in dominant hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) clones over time. Journal of Antimicrobial Chemotherapy, 2012; 67 (10): 2514 DOI: 10.1093/jac/dks245

Courtesy: ScienceDaily

Key Immune Cell May Play Role in Lung Cancer Susceptibility

Why do many heavy smokers evade lung cancer while others who have never lit up die of the disease? The question has vexed scientists for decades.

Now, new research at Washington University School of Medicine in St. Louis suggests a key immune cell may play a role in lung cancer susceptibility. Working in mice, they found evidence that the genetic diversity in natural killer cells, which typically seek out and destroy tumor cells, contributes to whether or not the animals develop lung cancer.

The research is published in September in Cancer Research.

“Overall, humans are genetically very similar but their immune systems are incredibly diverse,” explains senior author Alexander Krupnick, MD, a thoracic surgeon at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “Our findings add to the growing body of evidence suggesting that innate differences in immunity may determine not only a person’s susceptibility to colds but also to lung cancer.”

Based on the findings in mice, Krupnick says he and his colleagues now are studying whether humans have a similar genetic diversity in their natural killer cells. As part of a new clinical study, they’re analyzing the blood of heavy smokers with and without lung cancer and never-smokers with and without lung cancer to look for differences.

“We want to know whether heavy smokers who don’t get lung cancer have natural killer cells that are somehow better at destroying newly developing lung cancer cells,” says Krupnick, associate professor of surgery. “And, by comparison, do patients who have never smoked but develop lung cancer have weak natural killer cells?”

For the mouse study, the scientists evaluated three groups of mice with varying susceptibilities to lung tumors. After the mice were exposed to a carcinogen that causes lung cancer, one group readily developed the disease while another showed little evidence of the tumors. A third group experienced moderate tumor growth.

When the researchers depleted natural killers cells from the mice using an antibody, those that had been resistant to lung cancer developed large, aggressive tumors.

Further, in mice susceptible to lung cancer, the scientists showed that manipulating the immune system with a bone marrow transplant could significantly block the development of lung cancer. Their studies indicate that natural killer cells, not other types of immune cells like T cells or inflammatory cells, are responsible for this phenomenon.

In other types of cancers, including those of the breast, colon and prostate, T cells are capable of destroying tumor cells. But in lung cancer, scientists suspect that T cells become inactivated, which may give natural killer cells a more prominent role.

The researchers also traced the genetic diversity of the natural killer cells in the mice to a region of chromosome 6, which includes numerous genes that influence the effectiveness of these cells.

Moving forward, Krupnick and his team want to learn whether natural killer cells influence lung cancer susceptibility in people. “We need to identify those patients who are resistant to lung cancer and ask, ‘What is unique about their natural killer cells – are they more potent or do they produce more of them than people with lung cancer?’ The answer will determine our next steps.”

The research is supported by the ATX/Lungevity Foundation, the Alvin Siteman Cancer Center Internal Research Grant by the American Cancer Society, the National Institutes of Health (KO8CA131097) and Biostatistics Core (P30 Ca091842), the Rheumatic Diseases Core Center NIH (P30 AR48335), National Institutes of Health (1R01HL094601), The Barnes-Jewish Foundation, the American Association for Thoracic Surgery, Advancing a Healthier Wisconsin, Thoracic Surgery Foundation for Research and Education and the generous support of the Charlotte and Sheldon Rudnick.

Journal Reference:

1. D. Kreisel, A. E. Gelman, R. Higashikubo, X. Lin, H. G. Vikis, J. M. White, K. A. Toth, C. Deshpande, B. M. Carreno, M. You, S. M. Taffner, W. M. Yokoyama, J. D. Bui, R. D. Schreiber, A. S. Krupnick. Strain-Specific Variation in Murine Natural Killer Gene Complex Contributes to Differences in Immunosurveillance for Urethane-Induced Lung Cancer. Cancer Research, 2012; 72 (17): 4311 DOI: 10.1158/0008-5472.CAN-12-0908

Courtesy: ScienceDaily

Novel Approach for Single Molecule Electronic DNA Sequencing

DNA sequencing is the driving force behind key discoveries in medicine and biology. For instance, the complete sequence of an individual's genome provides important markers and guidelines for medical diagnostics and healthcare. Up to now, the major roadblock has been the cost and speed of obtaining highly accurate DNA sequences. While numerous advances have been made in the last 10 years, most current high-throughput sequencing instruments depend on optical techniques for the detection of the four building blocks of DNA: A, C, G and T. To further advance the measurement capability, electronic DNA sequencing of an ensemble of DNA templates has also been developed.

Recently, it has been shown that DNA can be threaded through protein nanoscale pores under an applied electric current to produce electronic signals at single molecule level. However, because the four nucleotides are very similar in their chemical structures, they cannot easily be distinguished using this technique. Thus, the research and development of a single-molecule electronic DNA sequencing platform is the most active area of investigation and has the potential to produce a hand-held DNA sequencer capable of deciphering the genome for personalized medicine and basic biomedical research.

A team of researchers at Columbia University, headed by Dr. Jingyue Ju (the Samuel Ruben-Peter G. Viele Professor of Engineering, Professor of Chemical Engineering and Pharmacology, Director of the Center for Genome Technology and Biomolecular Engineering), with colleagues at the National Institute of Standards and Technology (NIST) led by Dr. John Kasianowicz (Fellow of the American Physical Society), have developed a novel approach to potentially sequence DNA in nanopores electronically at single molecule level with single-base resolution. This work, entitled "PEG-Labeled Nucleotides and Nanopore Detection for Single Molecule DNA Sequencing by Synthesis" is now available in the open access online journal Scientific Reports, from Nature Publishing Group.

The reported nanopore-based sequencing by synthesis (Nano-SBS) strategy can accurately distinguish four DNA bases by detecting 4 different sized tags released from 5'-phosphate-modified nucleotides at the single molecule level for sequence determination. The basic principle of the Nano-SBS strategy is described as follows. As each nucleotide analog is incorporated into the growing DNA strand during the polymerase reaction, its tag is released by phosphodiester bond formation. The tags will enter a nanopore in the order of their release, producing unique ionic current blockade signatures due to their distinct chemical structures, thereby determining DNA sequence electronically at single molecule level with single base resolution.

As proof-of-principle, the research team attached four different length polymer tags to the terminal phosphate of 2'-deoxyguanosine-5'-tetraphosphate (a modified DNA building block) and demonstrated efficient incorporation of the nucleotide analogs during the polymerase reaction, as well as better than baseline discrimination among the four tags at single molecule level based on their nanopore ionic current blockade signatures. This approach coupled with polymerase attached to the nanopores in an array format should yield a single-molecule electronic Nano-SBS platform.

In previous work, the Center of Genome Technology & Biomolecular Engineering at Columbia University, led by Professor Ju and Dr. Nicholas J. Turro (William P. Schweitzer Professor of Chemistry), developed a four-color DNA sequencing by synthesis (SBS) platform using cleavable fluorescent nucleotide reversible terminators (NRT), which is licensed to Intelligent Bio-Systems, Inc., a QIAGEN company. SBS with cleavable fluorescent NRTs is the dominant approach used in the next generation DNA sequencing systems. Dr. Kasianowicz and his group at NIST pioneered the investigation of nanopores for single molecule analysis. They previously reported that different length polymers, polyethylene glycols (PEGs), could be distinguished by their unique effects on current readings in a α-hemolysin protein nanopores at single molecule level and subsequently developed a theory for the method. Their results provide the proof-of-concept for single molecule mass spectrometry. The combination of the SBS concept with the distinct nanopore-detectable electronic tags to label DNA building blocks led to the development of the single-molecule electronic Nano-SBS approach described the current Scientific Reports article (09/21/2012).

As lead author Dr. Shiv Kumar points out, "The novelty of our approach lies in the design and use of four differently tagged nucleotides, which upon incorporation by DNA polymerase, release four different size tags that are distinguished from each other at the single molecule level when they pass through the nanopore. This approach overcomes any constraints imposed by the small differences among the four nucleotides, a challenge which most nanopore sequencing methods have faced for decades." Moreover, the technique is quite flexible; with PEG tags as prototypes, other chemical tags can be chosen to provide optimal separation in different nanopore systems.

With further development of this Nano-SBS approach, such as the use of large arrays of protein or solid nanopores, this system has the potential to accurately sequence an entire human genome rapidly and at low cost, thereby enabling it to be used in routine medical diagnoses.

The authors of the Scientific Reports article were Shiv Kumar, Chuanjuan Tao, Minchen Chien, Brittney Hellner, Arvind Balijepalli, Joseph W.F. Robertson, Zengmin Li, James J. Russo, Joseph E. Reiner, John J. Kasianowicz, and Jingyue Ju. The study was supported by a grant from the National Institutes of Health, a National Research Council/NIST/NIH Research Fellowship, and a grant from the NIST Office of Law Enforcement Standards.

Journal Reference:

1. Shiv Kumar, Chuanjuan Tao, Minchen Chien, Brittney Hellner, Arvind Balijepalli, Joseph W. F. Robertson, Zengmin Li, James J. Russo, Joseph E. Reiner, John J. Kasianowicz, Jingyue Ju. PEG-Labeled Nucleotides and Nanopore Detection for Single Molecule DNA Sequencing by Synthesis. Scientific Reports, 2012; 2 DOI: 10.1038/srep00684

Courtesy: ScienceDaily

Diabetes Drug Could Help Fight Alzheimer's Disease, Study Reveals

A drug designed for diabetes sufferers could have the potential to treat neurodegenerative diseases like Alzheimer's, a study by scientists at the University of Ulster has revealed.

Type II diabetes is a known risk factor for Alzheimer's and it is thought that impaired insulin signalling in the brain could damage nerve cells and contribute to the disease.

Scientists believe that drugs designed to tackle Type II diabetes could also have benefits for keeping our brain cells healthy.

To investigate this, Prof Christian Hölscher and his team at the Biomedical Sciences Research Institute on the Coleraine campus used an experimental drug called (Val8)GLP-1.

This drug simulates the activity of a protein called GLP-1, which can help the body control its response to blood sugar. The scientists treated healthy mice with the drug and studied its effects in the brain.

Although it is often difficult for drugs to cross from the blood into the brain, the team found that (Val8)GLP-1 entered the brain and appeared to have no side-effects at the doses tested.

The drug promoted new brain cells to grow in the hippocampus, an area of the brain known to be involved in memory. This finding suggests that as well as its role in insulin signalling, GLP-1 may also be important for the production of new nerve cells in the mouse brain.

The team found that blocking the effect of GLP-1 in the brain made mice perform more poorly on learning and memory task, while boosting it with the drug seemed to have no effect on behaviour.

The new findings, published this week in the journal Brain Research, are part of ongoing research funded by Alzheimer's Research UK, the leading dementia research charity.

Prof Hölscher, said: "Here at the Biomedical Sciences Research Institute, we are really interested in the potential of diabetes drugs for protecting brain cells from damage and even promoting new brain cells to grow. This could have huge implications for diseases like Alzheimer's or Parkinson's, where brain cells are lost.

"It is very encouraging that the experimental drug we tested, (Val8)GLP-1, entered the brain and our work suggests that GLP-1 could be a really important target for boosting memory. While we didn't see benefits on learning and memory in these healthy mice, we are keen to test the drugs in mice with signs of Alzheimer's disease, where we could see real improvements."

Dr Simon Ridley, Head of Research at Alzheimer's Research UK, said: "We are pleased to have supported this early stage research, suggesting that this experimental diabetes drug could also promote the growth of new brain cells. While we know losing brain cells is a key feature of Alzheimer's, there is a long way to go before we would know whether this drug could benefit people with the disease.

"This research will help us understand the factors that keep nerve cells healthy, knowledge that could hold vital clues to tackling Alzheimer's. With over half a million people in the UK living with the disease, learning more about how to keep our brain cells healthy is of vital importance. Funding for dementia research lags far behind that of other common diseases, but is essential if we are to realise the true potential of research like this."

The Biomedical Science Research Institute (BMSRI) in Coleraine, is one of 15 University Research Institutes at Ulster and ranked second in the UK in the last national Research Assessment Exercise in 2008.

The BMSRI has been conducting pioneering research to investigate the underlying causes, diagnosis, treatment and prevention of human degenerative diseases."

Journal Reference:

1. Stephen F.J. McGovern, Kerry Hunter, Christian Hölscher. Effects of the glucagon-like polypeptide-1 analogue (Val⁸)GLP-1 on learning, progenitor cell proliferation and neurogenesis in the C57B/16 mouse brain. Brain Research, 2012; 1473: 204 DOI: 10.1016/j.brainres.2012.07.029

Courtesy: ScienceDaily

Nanoengineers Can Print 3-D Microstructures in Mere Seconds

Nanoengineers at the University of California, San Diego have developed a novel technology that can fabricate, in mere seconds, microscale three dimensional (3D) structures out of soft, biocompatible hydrogels. Near term, the technology could lead to better systems for growing and studying cells, including stem cells, in the laboratory. Long-term, the goal is to be able to print biological tissues for regenerative medicine. For example, in the future, doctors may repair the damage caused by heart attack by replacing it with tissue that rolled off of a printer.

Reported in the journal Advanced Materials, the biofabrication technology, called dynamic optical projection stereolithography (DOPsL), was developed in the laboratory of NanoEngineering Professor Shaochen Chen. Current fabrication techniques, such as photolithography and micro-contact printing, are limited to generating simple geometries or 2D patterns. Stereolithography is best known for its ability to print large objects such as tools and car parts. The difference, says Chen, is in the micro- and nanoscale resolution required to print tissues that mimic nature's fine-grained details, including blood vessels, which are essential for distributing nutrients and oxygen throughout the body. Without the ability to print vasculature, an engineered liver or kidney, for example, is useless in regenerative medicine. With DOPsL, Chen's team was able to achieve more complex geometries common in nature such as flowers, spirals and hemispheres. Other current 3D fabrication techniques, such as two-photon photopolymerization, can take hours to fabricate a 3D part.

The biofabrication technique uses a computer projection system and precisely controlled micromirrors to shine light on a selected area of a solution containing photo-sensitive biopolymers and cells. This photo-induced solidification process forms one layer of solid structure at a time, but in a continuous fashion. The technology is part of a new biofabrication technology that Chen is developing under a four-year, $1.5 million grant from the National Institutes of Health (R01EB012597). The Obama administration in March launched a $1 billion investment in advanced manufacturing technologies, including creating the National Additive Manufacturing Innovation Institute with $30 million in federal funding to focus on 3D printing. The term "additive manufacturing" refers to the way 3D structures are built layering very thin materials.

The Chen Research Group is focused on fabrication of nanostructured biomaterials and nanophotonics for biomedical engineering applications and recently moved into the new Structural and Materials Engineering Building, which is bringing nano and structural engineers, medical device labs and visual artists into a collaborative environment under one roof.

Journal Reference:

1. A. Ping Zhang, Xin Qu, Pranav Soman, Kolin C. Hribar, Jin W. Lee, Shaochen Chen, Sailing He. Rapid Fabrication of Complex 3D Extracellular Microenvironments by Dynamic Optical Projection Stereolithography. Advanced Materials, 2012; 24 (31): 4266 DOI: 10.1002/adma.201202024

Courtesy: ScienceDaily

Discovery of Essential Genes for Drug-Resistant Bacteria Reveals New, High-Value Drug Targets

Biomedical scientists collaborating on translational research at two Buffalo institutions are reporting the discovery of a novel, and heretofore unrecognized, set of genes essential for the growth of potentially lethal, drug-resistant bacteria. The study not only reveals multiple, new drug targets for this human infection, it also suggests that the typical methods of studying bacteria in rich laboratory media may not be the best way to identify much-needed antimicrobial drug targets.

The paper focuses on a Gram-negative bacteria called A. baumannii. It is published in the current issue of mBio, as an 'editor's choice' paper. The findings may be relevant to other Gram-negative bacteria as well.

A. baumannii is responsible for a growing number of hospital-acquired infections around the world. It can be fatal to patients with serious illnesses, the elderly and those who have had surgeries. Infections also have been seen in soldiers returning from Iraq and Afghanistan with battlefield injuries.

"Generally, healthy people don't get infected," explains lead author Timothy C. Umland, PhD, research scientist at Hauptman-Woodward Medical Research Institute (HWI) and professor of structural biology in the University at Buffalo School of Medicine and Biomedical Sciences. "But what's challenging about A. baumannii is that it can survive in the hospital environment and is very hard to eradicate with common disinfectants, leading to healthcare-associated infections."

Typically, the way that essential genes for microbial pathogens are found is by growing the bacteria under optimal conditions, says co-author Thomas A. Russo, MD, professor in the UB departments of medicine and microbiology and immunology. Genes found to be essential for growth are then entered into the Database of Essential Genes (DEG), which contains genes considered essential for the sustenance of each organism.

The researchers at HWI and UB decided to try to better understand what A. baumannii needs in order to grow when infecting patients.

"Laboratory conditions create a different type of environment from what happens in patients," Umland says, "where certain nutrients the bacteria need will be present in very low amounts and where the bacteria encounter immune and inflammatory responses. We were purposely trying to test for genes that are important for growth in these more realistic environments."

The team performed a genetic screen designed to identify bacterial genes absolutely required for the growth and survival of A. baumannii in human ascites, a peritoneal fluid that accumulates under a variety of pathologic conditions.

"We found that nearly all of these 18 genes had not been identified as essential in the DEG because they weren't necessary for growth in an ideal laboratory environment," explains Russo. "This is a large set of genes that has been flying under the radar."

He adds: "The biggest concern is that quite a few strains of A. baumannii are resistant to nearly all anti-microbial drugs and some strains are resistant to all of them. To make things worse, there are no new agents being tested for human use in the drug pipeline that are active against A. baumannii. This is a huge problem."

Not only do the new genes suggest brand new, high-value drug targets for A. baumannii infections, but the genes that have been identified may be relevant to other Gram-negative infections.

"So far, our computational models show that these genes seem to be conserved across Gram-negative infections, meaning that they may lead to new drugs that would be effective for other drug-resistant infections as well," says Umland.

The researchers who collaborated on the study are now pursuing antibacterial drug discovery efforts focused on the newly identified bacterial targets.

The research was funded by grants from the Telemedicine and Advance Technical Research Center of the U.S. Army Medical Research and Materiel Command, an interdisciplinary grant from UB and a VA Merit Review grant from the U.S. Department of Veterans Affairs.

Other co-authors are: L. Wayne Schultz, PhD, of HWI and UB, and Ulrike MacDonald, Janet M. Beanan and Ruth Olson of the UB Department of Medicine, the Department of Microbiology and Immunology and UB's Witebsky Center for Microbial Pathogenesis.

Journal Reference:

1. T. C. Umland, L. W. Schultz, U. MacDonald, J. M. Beanan, R. Olson, T. A. Russo. In Vivo-Validated Essential Genes Identified in Acinetobacter baumannii by Using Human Ascites Overlap Poorly with Essential Genes Detected on Laboratory Media. mBio, 2012; 3 (4): e00113-12 DOI: 10.1128/mBio.00113-12

Courtesy: ScienceDaily

Work With Germ-Killing Copper Could Save Thousands of Lives

When Adam Estelle graduated from the University of Arizona's materials science and engineering program four years ago, he had no idea he would be involved in saving thousands of lives.

Like most graduates, he was just hoping to find a job -- preferably in Tucson, Ariz., because he wasn't interested in big-city life. What happened next was a job offer from the Copper Development Association in New York City.

Fast-forward four years, and Estelle says, "I love New York more and more every day. And the most rewarding thing for me is the ability to work on a project centered on a technology that will save lives. That's immensely rewarding."

The technology is based on copper alloys that kill bacteria, fungi and viruses. The metals can be fashioned into everything from IV poles to sinks to bed rails -- just about anything that is frequently touched in hospitals.

While these surfaces might look benign, they're covered with organisms that contribute to hospital-acquired infections, the fourth leading cause of death in the United States, killing more people than AIDS and breast cancer combined. That's 2 million infections annually, and 100,000 deaths -- one infection for every 20 people admitted to hospitals.

While disease-causing organisms can lurk on stainless steel surfaces for two weeks, according to a recent UA research study, 99.9 percent die within two hours on surfaces that contain at least 60 percent copper, Estelle says.

Estelle has been working with four other engineers at the Copper Development Association, a not-for-profit trade group, to develop a market for copper alloys in the health care industry. They also have been helping manufacturers gear up for producing copper alloy products.

Part of that effort has involved gaining EPA certification for the antimicrobial effects of copper so manufacturers can advertise the health benefits of these products.

The second part, which has been Estelle's major focus for the past two years, was to retrofit the Ronald McDonald House in Charleston, S.C., with copper alloy stair railings, door hardware, sinks, faucets, counter tops, kitchen tables, chair arms, and other surfaces that are frequently touched by patients, visitors and staff.

This has been a win-win for everyone, Estelle explained, creating a safer environment for families and children, while at the same time helping the first wave of manufacturers tool up and commercialize lines of copper products that can now be marketed to hospitals.

"One of our first commercial products is a beautiful seamless counter top and sink bowl manufactured by Elkay Commercial Products," Estelle said. "We installed about forty of these in the Ronald McDonald House." Elkay is among ten manufacturers now marketing antimicrobial copper alloy products to the health care industry.

Surfaces at the Ronald McDonald House were swabbed and tested for bacteria for ten weeks before the new copper alloy products were installed. "Follow-up tests on the items converted to copper showed they carried 94 percent fewer bacteria," Estelle said. "We are now trying to recreate the Charleston project at other Ronald McDonald Houses around the world to create a safer living and working environment for the children, families and staff."

Now, with the Ronald McDonald House pilot project completed and EPA approval secured, the next step is to convince hospitals to replace traditional surfaces that are not worn out with copper alloy ones. New policies from the Centers for Medicare and Medicaid Services that go into effect next year should help spur this changeover. Treatment for hospital-acquired infections costs between $35 billion and $45 billion each year in the U.S., and Medicare and Medicaid will no long reimburse hospitals for that treatment if the infections are judged to have been preventable and a hospital mistake.

But even without the new rules, the changeover makes economic sense, Estelle explained. Under today's reimbursement system, individual hospitals spend $5 million on average each year to treat infections. "Even on the low end, it's $30,000 per infection," he said. Clinical trials at three hospitals funded by the U.S. Department of Defense have recently proved that copper surfaces can reduce infections in the intensive care unit by more than 50 percent.

Using published estimates, about 500,000 Americans will contract an infection this year in the ICU. This will cost our hospitals an additional $3.5 billion in treatment, and about 40,000 people will not survive the ordeal. The clinical trial results suggest that installing copper surfaces could cut these figures in half.

"By implementing these surfaces, hospitals can see real, continuous savings year after year," Estelle said. "This is a passive way to prevent infection that doesn't depend on human behavior, such as hand-washing or hydrogen peroxide vapor machines. There is no need for maintenance beyond the normal surface cleaning procedures that are already in place."

Working for a small company that is on the leading edge of developing a new market has been rewarding and challenging, Estelle said. While his engineering courses didn't teach all the skills he's needed, the problem-solving techniques he learned at UA certainly have helped.

"I get involved in everything from supply chain development and marketing to clinical trials, regulatory approvals, Congressional advocacy, and more," Estelle said. "This is really a multidisciplinary job, and a lot of it is business-oriented. There's a lot of on-the-job networking, and interfacing with different professionals."

"But the most rewarding thing for me is the ability to work on a project that centers on technology that will save lives," he said. "I'm a pretty lucky guy."

Story Source:

The above story is reprinted from materials provided by University of Arizona College of Engineering, via Newswise. 

Courtesy: ScienceDaily

Fathers Biologically Attuned to Their Children When Sleeping Nearby, Research Reveals

Mothers aren't the only ones who are biologically adapted to respond to children. New research from the University of Notre Dame shows that dads who sleep near their children experience a drop in testosterone. Previous research from humans and other species suggests this decrease might make men more responsive to their children's needs and help them focus on the demands of parenthood.

In a recent study, Notre Dame Anthropologist Lee Gettler shows that close sleep proximity between fathers and their children (on the same sleeping surface) results in lower testosterone compared to fathers who sleep alone.

The study will appear in the September 5 issue of the journal PLoS ONE.

Gettler sampled 362 fathers, all of whom were between 25-26 years old, and divided them according to their reported nighttime sleeping location: solitary sleepers, those who slept in the same room as their children, and those fathers who slept on the same surface as their children.

Fathers' testosterone levels were measured from saliva samples collected upon waking and again just prior to sleep. Though the waking hormone levels of the three groups showed no significant differences, fathers who slept on the same surface as their children showed the lowest evening testosterone.

"Human fathers' physiology has the capacity to respond to children," Gettler says. "Our prior research has shown that when men become fathers, their testosterone decreases, sometimes dramatically, and that those who spend the most time in hands-on care -- playing with their children, feeding them or reading to them -- had lower testosterone. These new results complement the original research by taking it one step further, showing that nighttime closeness or proximity between fathers and their kids has effects on men's biology, and it appears to be independent of what they are doing during the day."

Substantial research has been conducted on the sleep and breastfeeding physiology of mother-baby co-sleeping, but this is the first study to examine how father-child sleep proximity may affect men's physiology, and it is the first to explore the implications of co-sleeping for either mothers' or fathers' hormones.

In other species, testosterone is known to enhance male mating effort through its influence on muscle mass and behaviors related to competing with other males and attracting female attention. The hormone is thought to operate similarly in humans, and higher testosterone has been linked to behaviors that might conflict with effective fathering, such as risk taking and sensation seeking. Prior research found that men with lower testosterone reported greater sympathy or need to respond to infant cries relative to men with higher testosterone.

"There are so many intriguing possibilities here for future research: Why do fathers have lower testosterone when they sleep very close to their children? Does it reflect human fathers' roles in our evolutionary past? How much do fathers vary in their nighttime care when their kids are close by? How does co-sleeping change fathers' sleep architecture when we know that co-sleeping increases mothers' arousals and mothers sync to their infants' sleep patterns," says Gettler.

"Testosterone is a hormone that frequently is a part of public discourse, but the false idea that 'manliness' is exclusively driven by testosterone often dominates the conversation. There is growing evidence that men's physiology can respond to involved parenthood -- something that was long thought to be limited to women. This suggests to us that active fatherhood has a deep history in the human species and our ancestors. For some people, the social idea that taking care of your kids is a key component of masculinity and manliness may not be new, but we see increasing biological evidence suggesting that males have long embraced this role."

Journal Reference:

1. Lee T. Gettler, James J. McKenna, Thomas W. McDade, Sonny S. Agustin, Christopher W. Kuzawa. Does Cosleeping Contribute to Lower Testosterone Levels in Fathers? Evidence from the Philippines. PLoS ONE, 2012; 7 (9): e41559 DOI: 10.1371/journal.pone.0041559

Courtesy: ScienceDaily

Surprising New Roles for a Key Regulatory Enzyme of Blood Pressure

Many patients with hypertension are treated with ACE inhibitors. These drugs block the angiotensin converting enzyme (ACE) that regulates the salt and water balance of the body and raises blood pressure. Recent studies by a research team led by Professor Ken Bernstein (Cedars-Sinai Medical Center, Los Angeles, California, USA) have, however, significantly broadened the enzyme's known task spectrum: The enzyme also plays a key role in blood formation, renal development and male fertility. In addition, the researchers showed that ACE has a hitherto unexpected influence on the immune response.

At the 1st ECRC "Franz-Volhard" Symposium on Sept. 7, 2012 at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch, Professor Ken Bernstein reported that in mice an excess of ACE led to a much stronger immune response than usual. In animal experiments, not only could bacterial infections be combated more effectively, but also the growth of aggressive skin cancer (melanoma) in mice could be contained by a stronger response of the immune system. In contrast, if the mice lacked ACE, the immune cells worked less effectively.

In addition, ACE apparently has an influence on blood formation. It has been known for many years that, in humans, ACE inhibitors induce a small reduction of red blood cell levels. To elucidate the exact roles of ACE, the Bernstein's research team deactivated the genes in mice that normally provide the blueprint for the enzyme. As a consequence, these so-called "knock out" mice could no longer produce the enzyme. The examination of these mice revealed that they in fact had significantly fewer red blood cells. Also, the white blood cells in these animals were less functional. According to the researchers' studies, ACE evidently plays a role in the development of the different blood cells.

Bernstein's team also showed that ACE apparently plays an important role in the development of the kidneys. In mice that could not produce the enzyme, the small arteries and the tissue of the kidneys revealed pathological changes, and the urine flow was impaired.

According to these findings, male fertility is also associated with ACE. Male mice lacking ACE continued to produce sperm, but they were no longer able to reproduce. However, if in the mice not the enzyme itself, but rather a product of ACE -- namely the hormone angiotensin II -- was suppressed, they could continue to reproduce. Until now it was thought that ACE mainly exerts its effect through the production of angiotensin II. These results show, however, that ACE is enzymatically active and produces other active products apart from angiotensin II, for example in the testes.

Story Source:

The above story is reprinted from materials provided by Max Delbrück Center for Molecular Medicine. 

Courtesy: ScienceDaily

Microbiologists Find New Approach to Fighting Viral Illnesses

By discovering how certain viruses use their host cells to replicate, UC Irvine microbiologists have identified a new approach to the development of universal treatments for viral illnesses such as meningitis, encephalitis, hepatitis and possibly the common cold.

The UCI researchers, working with Dutch colleagues, found that certain RNA viruses hijack a key DNA repair activity of human cells to produce the genetic material necessary for them to multiply.

For many years, scientists have known that viruses rely on functions provided by their host cells to increase their numbers, but the UCI study -- led by microbiology & molecular genetics professor Bert Semler -- is the first to identify how the RNA-containing picornaviruses utilize a DNA repair enzyme to do so.

Study results appear in the early online edition of the Proceedings of the National Academy of Sciences the week of Aug. 20.

RNA viruses have ribonucleic acid as their genetic material (rather than deoxyribonucleic acid, or DNA). Notable human diseases caused by RNA viruses include SARS, influenza, hepatitis C, West Nile fever, the common cold and poliomyelitis.

The UCI and Dutch researchers examined one group of RNA viruses, called picornaviruses, using biochemical purification methods and confocal microscopy to see how they co-opt the functions of a cellular DNA repair enzyme called TDP2 to advance their replication process.

"These findings are significant because all known picornaviruses harbor the target for this DNA repair enzyme, despite the fact that their genetic material is made up of RNA rather than DNA. Thus, identifying drugs or small molecules that interfere with the interaction between the virus and TDP2 could result in a broad-spectrum treatment for picornaviruses," said Semler, who also directs UCI's Center for Virus Research.

By targeting a host cell function required for viral replication and not the virus itself, he added, the primary challenge of antiviral drug resistance may be sidestepped.

As part of their survival mechanism, RNA viruses mutate often, and drugs intended for them usually become ineffective over time. HIV, for example, rapidly mutates, necessitating a combination therapy employing a number of antiviral agents.

A drug that blocks RNA viruses from hijacking DNA repair enzymes may avoid these resistance issues. Semler's lab plans to screen mixtures of drug candidates to find ones that inhibit this process in cells infected by the human rhinovirus, the predominant cause of the common cold.

Richard Virgen-Slane, Janet Rozovics, Kerry Fitzgerald, Tuan Ngo, Wayne Chou and Paul Gershon of UCI and Gerbrand van der Heden van Noort and Dmitri Filippov of Leiden University in the Netherlands participated in the study, which received support from the American Asthma Foundation and a National Institutes of Health Public Health Service grant.

Journal Reference:

1. R. Virgen-Slane, J. M. Rozovics, K. D. Fitzgerald, T. Ngo, W. Chou, G. J. van der Heden van Noort, D. V. Filippov, P. D. Gershon, B. L. Semler. An RNA virus hijacks an incognito function of a DNA repair enzyme. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1208096109

courtesy: ScienceDaily

Potential Drug for Treatement of Alzheimer's Disease Investigated

A compound developed to treat neuropathic pain has shown potential as an innovative treatment for Alzheimer's disease, according to a study by researchers at Cleveland Clinic's Lerner Research Institute and Anesthesiology Institute.

"Cleveland Clinic dedicated two years of research into the examination of this compound and our findings show it could represent a novel therapeutic target in the treatment of Alzheimer's disease," said Mohamed Naguib, M.D., Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine. "Development of this compound as a potential drug for Alzheimer's would take many more years, but this is a promising finding worthy of further investigation."

In a study published online in the Neurobiology of Aging, the compound MDA7 induced beneficial immune responses that limited the development of Alzheimer's disease. Treatment with the compound restored cognition, memory and synaptic plasticity -- a key neurological foundation of learning and memory -- in an animal model.

Neuroinflammation is an important mechanism involved in the progression of Alzheimer's disease. The MDA7 compound has anti-inflammatory properties that act on the CB2 receptor -- one of the two cannabinoid receptors in the body -- but without the negative side effects normally seen with cannabinoid compounds.

Alzheimer's disease is an irreversible, fatal brain disease that slowly destroys memory and thinking skills. About 5 million people in the United States have Alzheimer's disease. With the aging of the population, and without successful treatment, there will be 16 million Americans and 106 million people worldwide with Alzheimer's by 2050, according to the 2011 Alzheimer's Disease Facts and Figures report from the Alzheimer's Association.

Journal Reference:

1. Jiang Wu, Bihua Bie, Hui Yang, Jijun J. Xu, David L. Brown, Mohamed Naguib. Activation of the CB2 receptor system reverses amyloid-induced memory deficiency. Neurobiology of Aging, 2012; DOI: 10.1016/j.neurobiolaging.2012.06.011

Courtesy: ScienceDaily

Genetic Link to Prostate Cancer Risk in African Americans Found

Prostate cancer in African-American men is associated with specific changes in the IL-16 gene, according to researchers at the University of Illinois at Chicago College of Medicine.

The study, published online in the journal Cancer Epidemiology, Biomarkers & Prevention, establishes the association of IL-16 with prostate cancer in men of both African and European descent.

"This provides us with a new potential biomarker for prostate cancer," says principal investigator Rick Kittles, UIC associate professor of medicine in hematology/oncology.

Previously identified changes in the gene for IL-16, an immune system protein, were associated with prostate cancer in men of European descent. But the same changes in the gene's coded sequence -- called "polymorphisms" -- did not confer the same risk in African Americans.

Doubt was cast on IL-16's role in prostate cancer when researchers were unable to confirm that the IL-16 polymorphisms identified in whites were also important risk factors in African Americans, Kittles said.

Kittles and his colleagues used a technique called imputation -- a type of statistical extrapolation -- that allowed them to see new patterns of association and identify new places in the gene to look for polymorphisms. They found changes elsewhere in the IL-16 gene that were associated with prostate cancer and that were unique to African Americans.

Polymorphisms result from DNA mutations and emerge in the ancestral history of different populations. People of African descent are much more genetically diverse than whites, Kittles said, making the search for polymorphisms associated with disease more difficult.

Although the effect of the particular changes to the gene appear to be different in men of African versus European descent, it is likely that several of the polymorphisms in the gene alter the function of the IL-16 protein.

"This confirms the importance of IL-16 in prostate cancer and leads us in a new direction," Kittles said. "Very little research has been done on IL-16, so not much is known about it."

"We now need to explore the functional role of IL-16 to understand the role it is playing in prostate cancer," he said.

Ken Batai, graduate student in the UIC Institute for Human Genetics, was first author of the study. Other authors were Ebony Shah, Jennifer Newsome, and Maria Ruden of the UIC Institute for Human Genetics; Adam Murphy of Northwestern University; and Chiledum Ahaghotu of Howard University Hospital in Washington, D.C.

The study was supported by grants from the Department of Defense (DAMD W81XWH-07-1-0203) and National Cancer Institute/National Institutes of Health (RC2-CA148085-01 and U01-CA136792-02S1.)

Journal Reference:

1. Ken Batai, Ebony Shah, Adam B. Murphy, Jennifer Newsome, Maria Ruden, Chiledum Ahaghotu, and Rick A. Kittles. Fine-mapping of IL-16 gene and prostate cancer risk in African Americans. Cancer Epidemiology, Biomarkers & Prevention, 2012; DOI: 10.1158/1055-9965.EPI-12-0707

Courtesy: ScienceDaily