Daily Archives: November 20, 2014

Real-time genome sequencing helps control hospital outbreak

Posted: November 20, 2014 at 11:44 pm

PUBLIC RELEASE DATE:

19-Nov-2014

Contact: Shane Canning shane.canning@biomedcentral.com 44-203-192-2243 BioMed Central @biomedcentral

Pioneering use of whole genome sequencing in real time to help control a hospital outbreak is reported in an article published in the open access journal Genome Medicine. The research corroborates the use of the technique as a rapid and cost-effective way of tracking and controlling the spread of drug-resistant hospital pathogens.

Acinetobacter baumannii is a multi-drug resistant pathogen found in hospitals across the globe and emerged as a significant threat to casualties in the Iraq and Afghanistan wars. It affects severely ill patients, particularly trauma and burns patients, often leading to pneumonia and bloodstream infections. Healthcare-associated infections (HAIs) are estimated to cost the UK 1 billion a year and, at any given time, one in every 15 patients will have a HAI.

Whole genome sequencing, which sequences an organism's entire DNA, is thought to be a promising new addition to the toolkit for controlling HAIs. Conventional methods are often applied retrospectively and yield limited information about a pathogen's DNA, making it difficult to compare whether patients are carrying the same bacteria and track transmission of outbreaks.

In this paper the researchers from the University of Birmingham, University of Warwick, and the National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, report how whole genome sequencing was used to control an outbreak of A. baumannii at Queen Elizabeth Hospital Birmingham in 2011. The outbreak began following the admittance of a military patient from Afghanistan with blast injuries and lasted for 80 weeks - making it one of the longest outbreaks ever described for this pathogen. The patient was carrying a novel strain of the bacterium that had not previously been observed in the region's hospitals. After first using traditional methods to try and contain the pathogen, the researchers decided to switch to whole genome sequencing mid-way through the outbreak.

Sampling patients and the environment, the researchers were able to identify 74 patients belonging to the outbreak. They then determined the detailed genetic makeup of the bacteria carried by each of these patients and used this data, with information about the ward that the patients were housed in, and the date of their first positive tests, to identify nearly 70 possible transmission events. Armed with this detailed information, the researchers were able to pinpoint transmission hot spots within the hospital, which included an operating theatre and a specialised bed for burns patients.

Deep cleaning of these transmission sites followed and new decontamination protocols were put in place by the hospital. In May 2013 the outbreak was declared closed. Lead author of the study, Mark Pallen from the University of Warwick, said: "We have demonstrated how whole genome sequencing can be applied in a clinically helpful timeframe to track and control the spread of drug-resistant hospital pathogens. In this case, it helped understand and control what was probably longest running A. baumannii outbreak ever seen in this country."

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Comparing The Genomes Of Mice And Humans To Aid Clinical Research

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Chuck Bednar for redOrbit.com Your Universe Online

An international research consortium investigating the functional genome of the mouse have managed to map the creatures so-called mission control centers, and found new clues as to why certain processes and systems in the rodents prevent the results of mouse studies from being successfully replicated in humans.

Members of the Mouse ENCODE project, a project designed to complement the National Human Genome Research Institutes (NHGRI) Encyclopedia of DNA Elements (ENCODE) program, were able to produce an exhaustive description of the functional genome elements of mice, and compared that information to the human genome. Their findings produced similarities between the two mammals, as well as some significant differences.

ENCODE, which began in 2003, analyzed specific components in the human genome responsible for gene expression, or the process of coding for proteins that carry out a cells function. The Mouse ENCODE study looked at 100 mouse cell types and tissues to annotate the regulatory elements of the mouse genome and compared them to the human genome useful research, since mice are so often used as model organisms in clinical studies.

According to the National Institutes of Health (NIH), which oversees the NHGRI, the researchers reported their findings in four separate studies published in the journal Nature and other prominent scientific journals. In those papers, the authors examined the genetic and biochemical programs involved in regulating both mouse and human genomes, finding that the systems responsible for controlling gene activity in each have many similarities that have been conserved through the evolutionary process.

Their findings could provide new insight into genetic regulation and other systems essential to mammalian biology, the NIH said. Furthermore, their work could provide new information to determine in which cases the mouse will continue to be an appropriate model for studies involving the effect of drugs and disease on humans, as well as help explain some of the limitations of this model and why the results of such studies sometimes fail to translate to people.

The mouse has long been a mainstay of biological research models, said NHGRI Director Dr. Eric Green. These results provide a wealth of information about how the mouse genome works, and a foundation on which scientists can build to further understand both mouse and human biology. The collection of mouse ENCODE data is a tremendously useful resource for the research community.

This is the first systematic comparison of the mouse and human at the genomic level, added Dr. Bing Ren, a professor of cellular and molecular medicine at University of California, San Diego (UCSD) and co-senior author of the Consortiums primary Nature study. We have known that the mouse was mostly a good model for humans [and] this allows us to study human disease by studying those aspects of mouse biology that reflect human biology.

Among the discoveries made during the course of the research was the discovery as to why the immune system, metabolism and stress response of mice are so different from humans, the Centre for Genome Regulation (CGR), one of the institutions involved in the project, explained. They compared various processes involved in gene expression, including gene transcription and chromatin modification, and repeated those investigations in various different tissues and cell types from both mice and humans.

Our lab took part in analyzing the group of RNA or transcriptome, that results from transcription, the process by which the instructions in the genes are read, said Alessandra Breschi, a CGR researcher and one of the first co-authors of the main study. We have discovered that human and mice transcriptome contains both preserved and divergent elements. Surprisingly we have found that the differences seem bigger between species rather than between fabrics when initially we thought that the gene activity in the same kinds of tissues would be similar.

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Cetaphil Restoraderm Restoring Formulated Eczema – Video

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Why I am sharing my eczema journey and what I deal with everyday living with eczema – Video

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Beauty Talk: Treating Eczema – Video

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Tampa dermatologist excited over eczema clinical trial results

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As his clinical trials for eczema continue, Tampa dermatologist Dr. Seth Forman says that the ongoing trials have produced encouraging results.

To this point, Dr. Forman has treated several patients that suffer from the uncomfortable skin condition in hopes of finding a breakthrough treatment that will alleviate eczema symptoms. In addition, the trials aim to achieve a noticeable improvement in the appearance of the skin for those participating.

We are very happy with the results, said Dr. Forman. My hope is that they continue to progress as we treat more patients.

Also known as atopic dermatitis, eczema is a medical skin condition characterized by inflammation and irritation of the epidermis. Common symptoms include itchiness and dryness of the skin and a development of thick red patches on areas of the body including the face, hands and neck.

Although trials have proven successful thus far, the Tampa dermatologist continues to encourage the involvement of new patients and volunteers.

This is a one-of-a-kind opportunity, said Dr. Forman. The more we perform these trials the closer we get to providing effective treatment for those who suffer from eczema.

Dr. Forman is the founder of Forman Dermatology and Skin institute, located in Tampa, Fla. and has appeared on TV shows across the country, including the nationally syndicated show The Doctors to provide sun-protection tips and to demonstrate his breakthrough skin cancer treatments.

If interested in being a part of the clinical trial for eczema, or for more on Dr. Seth Forman, Tampa dermatology or Forman Dermatology and Skin Cancer Institute, please visit http://www.FormanDerm.com.

About Dr. Seth Forman: Dr. Forman is a board-certified dermatologist practicing in Tampa, Florida. He was voted the Best Dermatologist in Carrollwood in 2011 and 2012 by the Carrollwood News and Tribune. In December 2011, he opened his new Tampa dermatology office, Forman Dermatology and Skin Cancer Institute, where he gives psoriasis sufferers access to the latest treatment options, including topical and oral medications, as well as biological and phototherapy. Dr. Forman is one of the few Tampa dermatologists to offer narrowband light therapy, which uses pharmaceutical grade light to suppress psoriasis. Hes also one of the few board-certified dermatologists in the U.S. to use the SRT-100 radiotherapy to treat basal cell carcinoma, the most common form of skin cancer.

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AYURVEDIC TREATMENT ON PSORIASIS AND ITS COMPLICATIONS : BY VAIDYA SAMIR JAMADAGNI SIR. – Video

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Gene therapy provides safe, long-term relief for patients with severe hemophilia B

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Gene therapy developed at St. Jude Children's Research Hospital, University College London (UCL) and the Royal Free Hospital has transformed life for men with a severe form of hemophilia B by providing a safe, reliable source of the blood clotting protein Factor IX that has allowed some to adopt a more active lifestyle, researchers reported. The results appear in the November 20 edition of The New England Journal of Medicine.

In this study, participants received one of three doses of gene therapy that used a modified adeno-associated virus (AAV) 8 as the vector to deliver the genetic material for making Factor IX. The vector was administered as a single infusion into a peripheral vein in the arm of each participant.

Factor IX levels rose in all 10 men with severe hemophilia B following gene therapy and have remained stable for more than four years. Overall, episodes of spontaneous bleeding declined 90 percent. Use of Factor IX replacement therapy dropped about 92 percent in the first 12 months after the treatment with the investigational therapy.

In the six participants who received the highest gene therapy dose, levels of the blood-clotting protein increased from less than 1 percent of normal levels to 5 percent or more. The increase transformed their disease from severe to mild and enabled participation in sports such as soccer without the need for Factor IX replacement therapy or an increase in the risk of bleeding. Episodes of spontaneous bleeding and use of Factor IX replacement therapy declined for these patients more than 94 percent in the next 12 months.

Liver enzymes rose in four of the six patients who received the highest dose, possibly due to an immune response against the vector. The men had no symptoms and remained otherwise healthy. Their liver enzymes returned to the normal range following brief treatment with steroids.

Hemophilia B is caused by a mutation in the Factor IX gene that can result in dangerously low levels of the essential clotting protein. The disorder affects about 1 in 30,000 individuals, mostly men. For those with severe disease marked by Factor IX levels less than 1 percent of normal, scrapes and bumps are medical emergencies. Painful episodes of spontaneous bleeding can result in crippling joint damage early in life and an increased risk of potentially fatal bleeding within the brain.

"This study provides the first clear demonstration of the long-term safety and efficacy of gene therapy," said senior author Andrew Davidoff, M.D., chair of the St. Jude Department of Surgery. "The results so far have made a profound difference in the lives of study participants by dramatically reducing their risk of bleeding."

The paper's first and corresponding author, Amit Nathwani, M.D., Ph.D., added: "The data we are reporting mark a paradigm shift in treatment of hemophilia B and lay the groundwork for curing this major bleeding disorder." Nathwani is a faculty member at the UCL Cancer Institute, Royal Free Hospital and NHS Blood and Transplant. "The results also provide a solid platform for developing this gene transfer approach for treatment of other disorders ranging from other congenital clotting deficiencies like hemophilia A to inborn errors of metabolism such as phenylketonuria."

Prior to receiving gene therapy, seven of the 10 men received Factor IX replacement therapy at least once a week in order to prevent bleeding episodes. Others used replacement therapy as needed to halt bleeding or prior to surgeries.

Since joining the trial, four of the seven men ended the routine Factor IX injections. None have suffered spontaneous bleeding despite increased physical activity. "Some patients have not required clotting factor injections for more four years, which has been life changing," Nathwani said. Researchers estimated that overall spending on Factor IX replacement therapy for study participants is down more than $2.5 million.

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Signaling molecule crucial to stem cell reprogramming

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PUBLIC RELEASE DATE:

20-Nov-2014

Contact: Scott LaFee slafee@ucsd.edu 619-543-5232 University of California - San Diego @UCSanDiego

While investigating a rare genetic disorder, researchers at the University of California, San Diego School of Medicine have discovered that a ubiquitous signaling molecule is crucial to cellular reprogramming, a finding with significant implications for stem cell-based regenerative medicine, wound repair therapies and potential cancer treatments.

The findings are published in the Nov. 20 online issue of Cell Reports.

Karl Willert, PhD, assistant professor in the Department of Cellular and Molecular Medicine, and colleagues were attempting to use induced pluripotent stem cells (iPSC) to create a "disease-in-a-dish" model for focal dermal hypoplasia (FDH), a rare inherited disorder caused by mutations in a gene called PORCN. Study co-authors V. Reid Sutton and Ignatia Van den Veyver at Baylor College of Medicine had published the observation that PORCN mutations underlie FDH in humans in 2007.

FDH is characterized by skin abnormalities such as streaks of very thin skin or different shades, clusters of visible veins and wartlike growths. Many individuals with FDH also suffer from hand and foot abnormalities and distinct facial features. The condition is also known as Goltz syndrome after Robert Goltz, who first described it in the 1960s. Goltz spent the last portion of his career as a professor at UC San Diego School of Medicine. He retired in 2004 and passed away earlier this year.

To their surprise, Willert and colleagues discovered that attempts to reprogram FDH fibroblasts or skin cells with the requisite PORCN mutation into iPSCs failed using standard methods, but succeeded when they added WNT proteins - a family of highly conserved signaling molecules that regulate cell-to-cell interactions during embryogenesis.

"WNT signaling is ubiquitous," said Willert. "Every cell expresses one or more WNT genes and every cell is able to receive WNT signals. Individual cells in a dish can grow and divide without WNT, but in an organism, WNT is critical for cell-cell communication so that cells distinguish themselves from neighbors and thus generate distinct tissues, organs and body parts."

WNT signaling is also critical in limb regeneration (in some organisms) and tissue repair.

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