#ReleaseTheCures !!!

Study Finds Widely Used Treatment for Infection Fails Young Cancer Patients

A treatment designed to reduce bloodstream infections due to central venous catheters that had worked well in lab studies and is commonly used around the world, but had not been rigorously tested, failed to protect young cancer patients from recurring or new infections and left them at higher risk for complications. St. Jude Children's Research Hospital investigators led the study, which appears online today in the journal The Lancet Infectious Diseases.

The study focused on the effectiveness of ethanol-lock therapy for treatment and prevention of bloodstream infections and related complications in pediatric cancer patients with central venous catheters, known as central lines.

Central lines are surgically implanted and connected to the bloodstream, making it easier to draw blood and deliver chemotherapy, fluids and other treatments without repeated needle sticks. But about 25 percent of pediatric cancer patients develop central line-associated bloodstream infections that disrupt cancer treatment and sometimes result in hospitalization, long-term complications or death. Despite antibiotic therapy, one-third of patients develop persistent or multiple infections and even more patients undergo additional surgery to replace central lines.

"Ethanol-lock therapy works in the laboratory to kill even tough-to-eradicate biofilm," said first and corresponding author Joshua Wolf, MBBS, an assistant member of the St. Jude Department of Infectious Diseases. "We knew anecdotally that ethanol-lock therapy is used at many hospitals in an effort to prevent new or recurring central line bloodstream infections in children with cancer."

But in a double-blind, randomized placebo-controlled clinical trial of children and young adults with cancer and blood disorders, Wolf and his colleagues found ethanol-lock therapy was no better than saline solution (placebo) at preventing new or repeat bloodstream infections. It was also no better than placebo at reducing central line replacement surgeries.

Worse, patients who received ethanol therapy were 2.5-times more likely than patients in the placebo group to develop catheter blockages that required treatment with blood thinners.

"Based on these results, ethanol-lock therapy should not be routinely used in children with cancer or hematologic disorders," Wolf said. "Serious bacterial infections remain a life-threatening problem that is the focus of intensive ongoing research."

The study included 94 patients being treated at St. Jude and in Australia at the Royal Children's Hospital, Melbourne. The patients were all receiving antibiotics for treatment of central line-associated bloodstream infections. The patients were randomly assigned to the same six-month schedule of central line treatment with either 70 percent ethanol solution or saline solution.

About 44 percent of patients in both groups developed new or recurring infections or required surgical replacement of central lines. In addition, 58 percent of patients in the ethanol group needed blood-thinners to open blocked central lines compared to about 33 percent in the placebo group.

The senior author is Patricia Flynn, MD, of St. Jude. The other authors are Kim Allison, Li Tang, Julie Richardson, Kristen Branum, Jeffrey Rubnitz, Aditya Gaur, Hana Hakim, Yin Su, Sara Federico and Randall Hayden, all of St. Jude; Tom Connell, Eloise Borello, Francoise Mechinaud, Paul Monagle and Nigel Curtis, all of the Royal Children's Hospital; and Leon Worth of the Peter MacCallum Cancer Centre, Melbourne, Australia.

The research was funded in part by the Australian Government Research Training Scholarship and ALSAC, the fundraising and awareness arm of St. Jude.

https:// www.infectioncontroltoday.com/infections/study-finds-widely-used-treatment-infection-fails-young-cancer-patients

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#ReleaseTheCures !!!

New Findings Could Lead to Treatment of Hepatitis B

Researchers at the University of Delaware, working with colleagues at Indiana University, have gained new insights into the virus that causes hepatitis B – a life-threatening and incurable infection that afflicts more than 250 million people worldwide. The discovery, which was published April 27 in the journal eLife, reveals previously unknown details about the capsid, or protein shell, that encloses the virus' genetic blueprint.

Scientists believe that the capsid, which drives the delivery of that blueprint to infect a host cell, is a key target in developing drugs to treat hepatitis B.

"With hepatitis B, the structure of the capsid has been known for years, but we wanted to study its motion and its influence on its surroundings," said Jodi A. Hadden, an independent postdoctoral researcher in UD's Department of Chemistry and Biochemistry and the lead author of the new paper.

Jodi Hadden and Juan Perilla have used computer simulations to learn more about the capsid, or protein shell, that encloses the genetic blueprint of the hepatitis B virus. An image of the capsid shows how it is made up of 240 proteins.

Hadden and the research team used supercomputing resources to perform what are known as all-atom molecular dynamics simulations.

Molecular dynamics simulations allow researchers to study the way molecules move in order to learn how they carry out their functions in nature. Computer simulations are the only method that can reveal the motion of molecular systems down to the atomic level and are sometimes referred to as the "computational microscope."

In the case of the simulations of the hepatitis B virus, the researchers found that the capsid is not rigid as previously thought, but is highly flexible. They also learned that it can distort into an asymmetric shape, which might allow it to squeeze through an opening into the nucleus of a cell the virus is infecting.

"We think that the capsid might need that ability to distort in order to correctly package its genetic blueprint and get it into the nucleus to generate new copies of the virus during the infection process," Hadden said.

Previous research has used experimental microscopes to study the capsid, which is made up of 240 proteins, but that work hasn't yielded high-resolution images of the complex structure, said Juan R. Perilla, assistant professor of chemistry and biochemistry and a co-author of the new paper.

"It seems clear that the flexibility of the [hepatitis B] capsid is a limiting factor" in the effectiveness of microscopy, he said.

By contrast, the simulations have been able to reveal a more complete picture of the capsid and how it moves, distorts and interacts with its environment, Hadden said. Each simulation involves 6 million atoms.

"We have all the details down to the atomic level," she said. "You need that to develop a complete understanding of the molecule and to study drug interactions."

The researchers also found that small triangular openings, or pores, in the capsid surface are likely the location where its protein "tails" poke through, sending a signal that is essential to the infection process.

"We know that the capsid tails have to be exposed to the surface at some time for the capsid to travel to the cell nucleus," Hadden said. "It's like hailing a taxi."

All the findings have the potential to lead to drug treatments, she said. For example, if the capsid could be made rigid and unable to distort or if a way could be found to block the triangular pores in its surface, the infection process might be halted.

There's an effective vaccine to prevent hepatitis B, but no cure once a person is infected. The virus causes severe liver disease, which can lead to potentially fatal conditions such as cirrhosis and liver cancer.

https:// www.infectioncontroltoday.com/hepatitis/new-findings-could-lead-treatment-hepatitis-b

FEMA Disaster Recovery Center closing Friday

The Federal Emergency Management Agency’s Disaster Recovery Center in Jacksonville is set to close permanently on Friday, according to the Calhoun County Emergency Management Agency.

That will be the last day for people to meet face-to-face with FEMA and Small Business Administration representatives said Jonathan Gaddy, Calhoun County EMA director. FEMA came to Jacksonville to assist residents who were affected by the tornado of March 19.

Gaddy said although the center is closing, people can still speak with FEMA online at disasterassitance.gov or by calling 800-621-3362. The registration deadline to receive any assistance is June 25.

Gaddy also said that storm victims who are renting or own a house, or have a business are eligible to receive SBA assistance.

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“It’s not only for businesses and that’s what everyone is not understanding,” he said. “They have to fill out the SBA loan application and wait to see if they’re approved. If they don’t fill it out then that’s the end of the road.”

Applications can be completed at the DRC before it closes on Friday, online or over the phone.

The center will operate on Friday from 10 a.m. to 6.p.m.

https:// www.annistonstar.com/free/fema-disaster-recovery-center-closing-friday/article_c945c492-69dc-11e8-a417-6b296be6c833.html