Treatment for IBS proves difficult, survey reveals

A new national survey by Health Union of more than 1,000 individuals with Irritable Bowel Syndrome (IBS) reveals that the condition is difficult to diagnose and often even more difficult to treat. Respondents often found healthcare providers and the public in general lacking in empathy and understanding of the full impact of the disease. Self-treatment often becomes the norm and controlling symptoms difficult.

IBS is a condition involving recurrent abdominal discomfort and pain accompanied by disordered bowel movements that occurs in roughly 10 to 15% of adolescents and adults in North America. Exact numbers are unknown, with vast underreporting due to many patients with IBS symptoms not consulting a physician and not being formally diagnosed. Symptoms include, but are not limited to, changes in bowel habits, such as constipation, diarrhea, or alternating occurrences of these. Other symptoms may include difficulty swallowing, acid reflux, and nausea.

The exact cause of IBS remains unknown, with multiple factors, including psychosocial, environmental, and gut physiology combining to produce symptoms. The lack of an exact cause leads to extreme difficulty in diagnosis. With no definitive diagnostic test, IBS is diagnosed through symptom-based guidelines. Sometimes symptoms may be mistakenly diagnosed as IBS when they can actually be signs of other conditions, such as celiac disease, inflammatory bowel disease, or colorectal cancer.

Along with diagnostic difficulties, patients find the severity of the condition and the impact on quality of life to be misunderstood. “So many with IBS go undiagnosed, and while it’s unfortunate, it’s not too surprising. When you hear ‘it’s just IBS’ it doesn’t exactly feel like you’ve received a proper diagnosis of a legitimate illness” said Stephanie Huston, IrritableBowelSyndrome.net patient contributor and Health Union employee.

There is no cure for IBS. Treatment focuses on improving gastrointestinal symptoms and improving quality of life. Most respondents report recognizing the triggers for their IBS, but still found it difficult to manage symptoms, with only 2% indicating they were able to manage all of their symptoms. The symptoms reported most difficult to manage were the urgent need to move bowels (77%), chronic/persistent diarrhea (67%), and frequent bowel movements (58%).

Related Stories

Treatment for IBS proves difficult and respondents often turned away from their healthcare providers (HCPs) in favor of self-care approaches. Four in ten reported being dissatisfied with their HCP, citing issues with empathy, education, communication and non-pharmaceutical approaches. Thirty-eight percent were not currently seeing an HCP, with 32% of those choosing to manage on their own and 27% not finding their HCP helpful in treating their IBS.

“I’ve seen a number of healthcare practitioners for my IBS, including physicians, naturopaths, and acupuncturists. Some have been more helpful than others, but through all my relationships and searching for the right solution for me, I’ve learned how to be a better advocate for my own health. No one can tell you what is best for you. They can offer suggestions and options, but it’s up to the individual to decide and to weigh the risks and benefits of each treatment option,” said patient contributor Emily Downward.

Respondents most often turned to diet and lifestyle changes to manage their IBS. Nearly all (98%) tried at least one diet strategy. Other top lifestyle changes included exercise (43%), use of probiotics (43%), and vitamins (44%). Only 15% of respondents have tried a prescription IBS medication and only 5% were currently using one.

Tim Armand, president and co-founder of Health Union, noted the difficulties IBS patients often face, stating: “Living with IBS can be very frustrating. Changing diet may help, but doesn’t always work to prevent symptoms, and other people don’t understand how much of an impact IBS has on daily life. We hope that IrritableBowelSyndrome.net can help fill the gap by providing information and community support that is often now lacking.”

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Health Union

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Treatment for IBS proves difficult, survey reveals

A new national survey by Health Union of more than 1,000 individuals with Irritable Bowel Syndrome (IBS) reveals that the condition is difficult to diagnose and often even more difficult to treat. Respondents often found healthcare providers and the public in general lacking in empathy and understanding of the full impact of the disease. Self-treatment often becomes the norm and controlling symptoms difficult.

IBS is a condition involving recurrent abdominal discomfort and pain accompanied by disordered bowel movements that occurs in roughly 10 to 15% of adolescents and adults in North America. Exact numbers are unknown, with vast underreporting due to many patients with IBS symptoms not consulting a physician and not being formally diagnosed. Symptoms include, but are not limited to, changes in bowel habits, such as constipation, diarrhea, or alternating occurrences of these. Other symptoms may include difficulty swallowing, acid reflux, and nausea.

The exact cause of IBS remains unknown, with multiple factors, including psychosocial, environmental, and gut physiology combining to produce symptoms. The lack of an exact cause leads to extreme difficulty in diagnosis. With no definitive diagnostic test, IBS is diagnosed through symptom-based guidelines. Sometimes symptoms may be mistakenly diagnosed as IBS when they can actually be signs of other conditions, such as celiac disease, inflammatory bowel disease, or colorectal cancer.

Along with diagnostic difficulties, patients find the severity of the condition and the impact on quality of life to be misunderstood. “So many with IBS go undiagnosed, and while it’s unfortunate, it’s not too surprising. When you hear ‘it’s just IBS’ it doesn’t exactly feel like you’ve received a proper diagnosis of a legitimate illness” said Stephanie Huston, IrritableBowelSyndrome.net patient contributor and Health Union employee.

There is no cure for IBS. Treatment focuses on improving gastrointestinal symptoms and improving quality of life. Most respondents report recognizing the triggers for their IBS, but still found it difficult to manage symptoms, with only 2% indicating they were able to manage all of their symptoms. The symptoms reported most difficult to manage were the urgent need to move bowels (77%), chronic/persistent diarrhea (67%), and frequent bowel movements (58%).

Related Stories

Treatment for IBS proves difficult and respondents often turned away from their healthcare providers (HCPs) in favor of self-care approaches. Four in ten reported being dissatisfied with their HCP, citing issues with empathy, education, communication and non-pharmaceutical approaches. Thirty-eight percent were not currently seeing an HCP, with 32% of those choosing to manage on their own and 27% not finding their HCP helpful in treating their IBS.

“I’ve seen a number of healthcare practitioners for my IBS, including physicians, naturopaths, and acupuncturists. Some have been more helpful than others, but through all my relationships and searching for the right solution for me, I’ve learned how to be a better advocate for my own health. No one can tell you what is best for you. They can offer suggestions and options, but it’s up to the individual to decide and to weigh the risks and benefits of each treatment option,” said patient contributor Emily Downward.

Respondents most often turned to diet and lifestyle changes to manage their IBS. Nearly all (98%) tried at least one diet strategy. Other top lifestyle changes included exercise (43%), use of probiotics (43%), and vitamins (44%). Only 15% of respondents have tried a prescription IBS medication and only 5% were currently using one.

Tim Armand, president and co-founder of Health Union, noted the difficulties IBS patients often face, stating: “Living with IBS can be very frustrating. Changing diet may help, but doesn’t always work to prevent symptoms, and other people don’t understand how much of an impact IBS has on daily life. We hope that IrritableBowelSyndrome.net can help fill the gap by providing information and community support that is often now lacking.”

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Health Union

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TSRI scientists develop new strategy to design potential HIV vaccine candidates

Want to catch a criminal? Show a mugshot on the news.

Want to stop HIV infections? Get the immune system to recognize and attack the virus’s tell-tale structure.

That’s part of the basic approach behind efforts at The Scripps Research Institute (TSRI) to design an AIDS vaccine. This strategy may hinge on finding new ways to stabilize proteins called HIV-1 surface antigens and in designing HIV-like particles to prompt the body to fight the real virus.

Now two new studies led by TSRI scientists advance these efforts. The first describes a strategy to stabilize an important HIV structure and potentially create HIV lookalikes for large-scale vaccine production. The second study engineers novel nanoparticles as vaccine candidates, using this new knowledge.

“This is a big accomplishment in terms of engineering and design,” said TSRI biologist Jiang Zhu.

Zhu co-led the first study with Ian Wilson, Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI, and co-led the second with TSRI Associate Professor Andrew Ward.

The findings were published June 28, 2016 in the journal Nature Communications.

Stabilizing HIV

In the first publication, Zhu and researcher Leo Kong (a study first author now at the National Institutes of Health) built on previous structural studies from the Ward and Wilson labs to investigate a trait called “metastability.” Metastability describes the tense state of the HIV Envelope glycoprotein (Env) trimer when it is poised like a loaded spring to undergo the dramatic changes that allow the virus to enter cells.

Metastability poses a problem for scientists who want to create a precise image of this viral target and see what the human immune system is up against.

Metastability also stands in the way of naturally occurring immunity and vaccine production. For the adaptive immune system to work in either case, it needs to recognize a functional, stable version of a virus’s proteins—a sort of mugshot—so it can produce antibodies and attack the actual virus upon encountering it.

Unfortunately, because of the virus’s metastability, or shape-shifting tendency, structures of HIV’s proteins have proven difficult to establish for use in vaccine design. The Ward and Wilson groups at TSRI have previously determined cryo-EM and x-ray structures for other Env constructs; however, current methods to stabilize Env in one strain of HIV won’t necessarily stabilize it in another, making it hard to design an arsenal of Env proteins to help elicit “broadly neutralizing antibodies” that could fight many types of HIV.

To advance the vaccine effort, TSRI researchers wanted to track down the root cause of metastability, and Jiang and Kong hypothesized that altering a key region of Env would improve its overall properties.

They hypothesized that a region of the Env called HR1 could be linked to metastability.

“The HR1 basically resembles a highly bent twig that is ready to spring back straight,” said Kong. “This small bend in the HR1 region is likely ground zero for metastability. In most published Env structures, this region appears disordered when mutated or loosely packed when in its native form. From these observations, it seemed reasonable that rewiring the HR1 bend could greatly stabilize Env.”

Indeed, when the scientists tweaked HIV’s genetic sequence, they were able to shorten the HR1 region, preventing its transformation and keeping the rest of the structure stable.

“We’ve figured out one of the fundamental reasons why HIV is metastable,” said Zhu.

Related Stories

The researchers then demonstrated that their stabilized Env trimers also almost perfectly mimicked the structure of the real HIV trimer, suggesting they could be useful in vaccines. Since rewiring the HR1 should prevent Env undergoing its necessary shape-shifting changes to infect cells, the stabilization strategy also could lead to protein or DNA-based vaccines. Furthermore, the modified trimer also has the potential to be produced in reasonably large quantities and at high purity—important considerations in industrial-scale vaccine production.

Finally, since many viruses contain metastable Env proteins with HR1-like regions, this TSRI-developed engineering approach may be applicable in the design of vaccines against other viral pathogens such as influenza and Ebola virus.

New Vaccine Candidates

In the second paper, the researchers looked into designing nanoparticles that could mimic HIV.

Particles aren’t new in vaccine design. They provide the backbone of successful vaccines against human papillomavirus (HPV), hepatitis B and hepatitis E—”the most efficacious human vaccines ever made,” according to Zhu.

These nanoparticles are called virus-like particles (VLPs) and are hollow shells of other proteins found in nature. Scientists have found that they can add viral proteins to the outside of a shell, creating a phony virus. The imposter then prompts the body to produce antibodies for long-term protection against the real virus.

But as Zhu and his colleagues focused on creating HIV-like VLPs, the Env trimer, once again, presented a challenge.

The trimer is made of three subunits that come together to form a base with a crown shape on top. The top of the crown is where the tips of the three subunits meet.

Scientists have found that the immune system cannot produce broadly neutralizing antibodies when a vaccine contains only one part of the trimer. The immune system needs to see intact HIV proteins—also called antigens when they stimulate the immune system to create antibodies—in their native trimeric context.

To construct an artificial virus, in the new study the researchers added HIV trimers to nanoparticles that naturally lock their own subunits together in clusters of three. As the three subunits come together, the researchers hypothesized, they could bring the HIV antigens together to form a trimer.

“Our idea was to ‘fuse’ a trimeric HIV-1 antigen to a nanoparticle subunit, so when the subunits ‘self-assemble’ they bring three attached HIV-1 antigens together,” said TSRI Staff Scientist Linling He, who served as co-first author of the study with Natalia de Val, a researcher at TSRI at the time of the study.

It was a feat of geometry and engineering—and it worked. “It has been really challenging to properly present HIV Env on nanoparticles while keeping its natural trimeric form—but we did it,” said Zhu, “Multiple copies of Env are now displayed on the nanoparticle surface, just like what a real virus would do.”

The team then tested different nanoparticles and versions of the trimer, including one based on the stabilized Env in the first study, to find the best combinations. Six designs worked well in laboratory tests and now await trials in animal models.

“We are still pushing hard to find new vaccine candidates to elicit a protective response in humans,” said Wilson. “The challenges going forward are to understand how to use these new vaccine candidates to induce a protective broadly neutralizing antibody response and to develop the appropriate regimens to initiative this response.”

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Scripps Research Institute

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TSRI scientists develop new strategy to design potential HIV vaccine candidates

Want to catch a criminal? Show a mugshot on the news.

Want to stop HIV infections? Get the immune system to recognize and attack the virus’s tell-tale structure.

That’s part of the basic approach behind efforts at The Scripps Research Institute (TSRI) to design an AIDS vaccine. This strategy may hinge on finding new ways to stabilize proteins called HIV-1 surface antigens and in designing HIV-like particles to prompt the body to fight the real virus.

Now two new studies led by TSRI scientists advance these efforts. The first describes a strategy to stabilize an important HIV structure and potentially create HIV lookalikes for large-scale vaccine production. The second study engineers novel nanoparticles as vaccine candidates, using this new knowledge.

“This is a big accomplishment in terms of engineering and design,” said TSRI biologist Jiang Zhu.

Zhu co-led the first study with Ian Wilson, Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI, and co-led the second with TSRI Associate Professor Andrew Ward.

The findings were published June 28, 2016 in the journal Nature Communications.

Stabilizing HIV

In the first publication, Zhu and researcher Leo Kong (a study first author now at the National Institutes of Health) built on previous structural studies from the Ward and Wilson labs to investigate a trait called “metastability.” Metastability describes the tense state of the HIV Envelope glycoprotein (Env) trimer when it is poised like a loaded spring to undergo the dramatic changes that allow the virus to enter cells.

Metastability poses a problem for scientists who want to create a precise image of this viral target and see what the human immune system is up against.

Metastability also stands in the way of naturally occurring immunity and vaccine production. For the adaptive immune system to work in either case, it needs to recognize a functional, stable version of a virus’s proteins—a sort of mugshot—so it can produce antibodies and attack the actual virus upon encountering it.

Unfortunately, because of the virus’s metastability, or shape-shifting tendency, structures of HIV’s proteins have proven difficult to establish for use in vaccine design. The Ward and Wilson groups at TSRI have previously determined cryo-EM and x-ray structures for other Env constructs; however, current methods to stabilize Env in one strain of HIV won’t necessarily stabilize it in another, making it hard to design an arsenal of Env proteins to help elicit “broadly neutralizing antibodies” that could fight many types of HIV.

To advance the vaccine effort, TSRI researchers wanted to track down the root cause of metastability, and Jiang and Kong hypothesized that altering a key region of Env would improve its overall properties.

They hypothesized that a region of the Env called HR1 could be linked to metastability.

“The HR1 basically resembles a highly bent twig that is ready to spring back straight,” said Kong. “This small bend in the HR1 region is likely ground zero for metastability. In most published Env structures, this region appears disordered when mutated or loosely packed when in its native form. From these observations, it seemed reasonable that rewiring the HR1 bend could greatly stabilize Env.”

Indeed, when the scientists tweaked HIV’s genetic sequence, they were able to shorten the HR1 region, preventing its transformation and keeping the rest of the structure stable.

“We’ve figured out one of the fundamental reasons why HIV is metastable,” said Zhu.

Related Stories

The researchers then demonstrated that their stabilized Env trimers also almost perfectly mimicked the structure of the real HIV trimer, suggesting they could be useful in vaccines. Since rewiring the HR1 should prevent Env undergoing its necessary shape-shifting changes to infect cells, the stabilization strategy also could lead to protein or DNA-based vaccines. Furthermore, the modified trimer also has the potential to be produced in reasonably large quantities and at high purity—important considerations in industrial-scale vaccine production.

Finally, since many viruses contain metastable Env proteins with HR1-like regions, this TSRI-developed engineering approach may be applicable in the design of vaccines against other viral pathogens such as influenza and Ebola virus.

New Vaccine Candidates

In the second paper, the researchers looked into designing nanoparticles that could mimic HIV.

Particles aren’t new in vaccine design. They provide the backbone of successful vaccines against human papillomavirus (HPV), hepatitis B and hepatitis E—”the most efficacious human vaccines ever made,” according to Zhu.

These nanoparticles are called virus-like particles (VLPs) and are hollow shells of other proteins found in nature. Scientists have found that they can add viral proteins to the outside of a shell, creating a phony virus. The imposter then prompts the body to produce antibodies for long-term protection against the real virus.

But as Zhu and his colleagues focused on creating HIV-like VLPs, the Env trimer, once again, presented a challenge.

The trimer is made of three subunits that come together to form a base with a crown shape on top. The top of the crown is where the tips of the three subunits meet.

Scientists have found that the immune system cannot produce broadly neutralizing antibodies when a vaccine contains only one part of the trimer. The immune system needs to see intact HIV proteins—also called antigens when they stimulate the immune system to create antibodies—in their native trimeric context.

To construct an artificial virus, in the new study the researchers added HIV trimers to nanoparticles that naturally lock their own subunits together in clusters of three. As the three subunits come together, the researchers hypothesized, they could bring the HIV antigens together to form a trimer.

“Our idea was to ‘fuse’ a trimeric HIV-1 antigen to a nanoparticle subunit, so when the subunits ‘self-assemble’ they bring three attached HIV-1 antigens together,” said TSRI Staff Scientist Linling He, who served as co-first author of the study with Natalia de Val, a researcher at TSRI at the time of the study.

It was a feat of geometry and engineering—and it worked. “It has been really challenging to properly present HIV Env on nanoparticles while keeping its natural trimeric form—but we did it,” said Zhu, “Multiple copies of Env are now displayed on the nanoparticle surface, just like what a real virus would do.”

The team then tested different nanoparticles and versions of the trimer, including one based on the stabilized Env in the first study, to find the best combinations. Six designs worked well in laboratory tests and now await trials in animal models.

“We are still pushing hard to find new vaccine candidates to elicit a protective response in humans,” said Wilson. “The challenges going forward are to understand how to use these new vaccine candidates to induce a protective broadly neutralizing antibody response and to develop the appropriate regimens to initiative this response.”

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Scripps Research Institute

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First baby with Zika-related birth defect microcephaly born in Florida

Hillsborough County mosquito control drives through a neighborhood spraying against mosquitos in Hillsborough County, Florida, February 2, 2016. REUTERS/Scott Audette
Hillsborough County mosquito control drives through a neighborhood spraying against mosquitos in Hillsborough County, Florida, February 2, 2016.

Reuters/Scott Audette


A Haitian woman in Florida has delivered the first baby in the state born with the birth defect microcephaly caused by the Zika virus, Florida’s health department said on Tuesday.

The mother contracted the mosquito-borne virus in her home country and traveled to Florida to give birth, state officials said in statements.

If confirmed by the U.S. Centers for Disease Control and Prevention, the child will be the fifth in the United States to be born with a birth defect linked with travel to a country in which Zika is circulating.

Another four pregnant women lost their babies as a result of travel-related Zika infections, according to the latest CDC report as of June 16. So far, there have not been any cases of Zika in the United States arising from local mosquito transmission.

The CDC’s U.S. Zika Pregnancy Registry does not specify the states where those cases occurred. Cases of babies with microcephaly previously were reported in Hawaii and New Jersey.

U.S. health officials have concluded that Zika infections in pregnant women can cause microcephaly, a birth defect marked by unusually small head size and potentially severe developmental problems.

The U.S. cases so far involve women who contracted the virus outside the United States in areas with active Zika outbreaks, or were infected through unprotected sex with an infected partner.

Health experts expect local transmission to occur in the United States as mosquito season gets underway, particularly in states such as Florida and Texas.

Florida Governor Rick Scott signed an executive order last week that allocated about $26 million for Zika preparation and response in the state. But in Washington on Tuesday, funding to battle the virus failed to advance in the U.S. Senate.

The connection between Zika and microcephaly first came to light last fall in Brazil, which has now confirmed more than 1,400 cases of microcephaly that it considers to be related to Zika infections in the mothers.

The World Health Organization has said there is strong scientific consensus that Zika also can cause Guillain-Barre, a rare neurological syndrome that causes temporary paralysis in adults.

(Reporting by Colleen Jenkins; Editing by Julie Steenhuysen and Bernard Orr)


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California gets go-ahead to vote on legalization of marijuana


Californians are set to decide whether to make recreational marijuana use legal, as other Western states have done, after the California Secretary of State’s office said on Tuesday the issue could be put to voters in the November ballot.

The proposed so-called “Adult Use of Marijuana Act,” which is supported by Lieutenant Governor Gavin Newsom among others, would allow people aged 21 and older to possess as much as an ounce of marijuana for private recreational use and permit personal cultivation of as many as six marijuana plants.

“Today marks a fresh start for California, as we prepare to replace the costly, harmful and ineffective system of prohibition with a safe, legal and responsible adult-use marijuana system that gets it right and completely pays for itself,” initiative spokesman Jason Kinney said in a statement.

The measure would also establish a system to license, regulate and tax sales of marijuana, while allowing city governments to exercise local control over or disallow commercial distribution within their borders.

The initiative required just over 402,000 valid signatures to qualify for the ballot and exceeded that number on Tuesday, the Secretary of State’s office said. Secretary Alex Padilla is slated to certify the initiative on June 30.

Opinion polls show attitudes have shifted more in favor of liberalized marijuana laws since California voters defeated a recreational cannabis initiative in 2010.

California led the way in legalizing marijuana for medical purposes in 1996, with 22 other states and the District of Columbia following suit, although cannabis remains classified as an illegal narcotic under U.S. law.

Voters in four states – Colorado, Washington, Oregon and Alaska – plus the District of Columbia, have gone a step further since 2012 in permitting recreational use for adults. Voters in several more states will consider similar legislation in November as well.

Opponents of liberalized marijuana laws have argued that such measures carry public safety risks and would make pot more accessible to youngsters.

A new survey out last week showed however that marijuana consumption by Colorado high school students has dipped slightly since the state first permitted recreational cannabis use by adults.

(Reporting by Curtis Skinner in San Francisco; Editing by Brendan O’Brien and Simon Cameron-Moore)


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Advancing Health Equity for Sexual and Gender Minorities

Advancing Health Equity for Sexual and Gender Minorities

June 28
by Centers for Medicare & Medicaid Services

By: Cara V. James, Ph.D., Director of the Office of Minority Health at the Centers for Medicare & Medicaid Services

Each June we celebrate National Lesbian, Gay, Bisexual, and Transgender (LGBT) Pride Month by increasing awareness of sexual and gender minority populations’ health disparities and advances in promoting health equity for all.

However, despite making progress on a state and national level with inclusive policies, this June we have been reminded that there are still many challenges to overcome. In many places young people are still distanced from their families because of their sexual orientation and gender identity. For many sexual and gender minorities in the U.S. it is still difficult to be out to family, friends, and co-workers. A survey of U.S. adults found that more than 75% of lesbian, gay, or bisexual respondents reported experiencing discrimination in their lifetime. Experiences of discrimination and unfair treatment have been linked to poor health outcomes among older adults who identify as lesbian, gay, bisexual, and transgender (LGBT). These stressors and impacts are amplified when individuals identify with multiple marginalized groups (e.g., sexual, gender, and/or racial minority). That said, studies have shown that LGBT individuals who have good social support have higher self-esteem, a more positive group identity, and more positive mental health.

Although we commonly speak about the LGBT community as a single population it is important to remember that it is actually made up of many diverse individuals from many unique backgrounds and just about as many different ways of identifying themselves. At CMS it is especially important to remember that racial and ethnic minorities, people with disabilities, and older adults may also be sexual and gender minorities.

The CMS Office of Minority Health strives to increase understanding and awareness of disparities, create and share solutions to address those disparities, and implement effective actions to achieve health equity. To that end, we are developing a web-based training to aid providers in the collection of sexual orientation and gender identity (SOGI) data. We are working on a new best practices tool box for providing culturally and linguistically appropriate services (CLAS) with an emphasis on sexual and gender minorities and people with disabilities.

What can you do? Get informed. Learn more about health disparities for sexual minorities age 65 and older in CMS’ June data brief. Find out about the Office for Civil Rights’ rule highlighting your right to be free from discrimination in health careimplementing regulations under on the basis of sex, including sex stereotyping and gender identity. You can also learn more about LGBT health and well-being by looking at the work of our sister agencies within HHS. Think about how you can contribute to bringing health equity to your work. We encourage you to join us on the path to health equity by using the resources discussed in this blog, bookmarking the CMS OMH website, joining our listserv, and of course building on your own health equity activities!

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Virus-like elements within human genome linked to development of lupus and Sjogren's syndrome

Researchers at Hospital for Special Surgery (HSS) have uncovered a potential genetic trigger of systemic autoimmune disease. The study, the culmination of more than 10 years of research and published online in the journal Arthritis & Rheumatology in June, discovered virus-like elements within the human genome linked to the development of two autoimmune diseases: lupus and Sjogren’s syndrome.

An autoimmune disorder occurs when the body’s immune system malfunctions. Instead of protecting the body, it attacks and destroys healthy organs. More than 80 types of autoimmune disorders, including rheumatoid arthritis, lupus and Sjogren’s syndrome, affect up to 22 million people in the United States, according to the National Institutes of Health.

The precise cause of autoimmune diseases remains a mystery, but most scientists believe a combination of genetic and environmental factors come into play. For example, viral infections have been linked to the development of these disorders.

For their study, HSS researchers hypothesized that the abnormal expression of genetic elements known as LINE-1 ( L1) retroelements might trigger an innate immune response similar to that produced by outside viruses and contribute to an overproduction of interferons. Interferons are molecules our body produces in the presence of viruses and other pathogens to mobilize the immune system.

In healthy individuals, interferon is part of the complex immune response to combat danger. However, if levels of interferon are too high, instead of playing a protective role it can contribute to the development of autoimmune disease.

“In a number of these diseases, such as lupus and Sjogren’s syndrome, a class of interferon known as type 1 interferon is made in abundance and plays a key role, contributing to the immune dysfunction,” said Mary K. Crow, MD, physician-in-chief at Hospital for Special Surgery and senior study author.

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Investigators set out to discover why interferon was being produced in excess. “We hypothesized that virus-like DNA sequences inherent in our own genomes or the RNA transcripts they produce might be driving the production of interferon and contributing to disease,” said Dr. Crow, chair, Department of Medicine, and Benjamin M. Rosen Chair in Immunology and Inflammation Research at HSS. “Our genomes are packed with sequences derived from viruses that were inserted many thousands of years ago, and these virus-like sequences can move around, causing genetic mutations and contributing to the evolution of our genomes. We hypothesized that they sometimes generate virus-like RNA sequences that can be detected by the immune system.”

Researchers studied kidney biopsy samples from 24 patients with lupus nephritis and salivary gland tissue from 31 patients with Sjogren’s syndrome and compared them to healthy tissue.

“Our findings support the hypothesis that L1 retroelements, perhaps along with other virus-derived genomic elements, may contribute to the development of autoimmune disorders characterized by high levels of type 1 interferon,” she said. “Although it may not be the only cause, it’s intriguing to think that virus-derived elements in our own genome are either quiet and don’t cause any trouble, or they get stirred up and contribute to disease.”

Further studies are needed to elucidate the role of both exogenous and endogenous viruses in the development of autoimmune disease, Dr. Crow said. Gaining a better understanding of the underlying disease mechanisms could offer the possibility of developing new and better treatments for lupus and other autoimmune conditions in the future.

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TSRI scientists identify GlyRS protein that launches cancer growth

Scientists at The Scripps Research Institute (TSRI) have identified a protein that launches cancer growth and appears to contribute to higher mortality in breast cancer patients.

The new findings, published June 27, 2016 in the journal Nature Structural & Molecular Biology, suggest that future therapies might target this protein, called GlyRS, to halt cancer growth.

“We have potentially found an important target for anti-cancer treatment,” said TSRI Professor Xiang-Lei Yang, who led the study.

Catching a Double Agent

Since the early days of life on Earth, GlyRS has played a role in protein synthesis, helping cells function and grow.

The new study, a collaboration with Professor Patrick Griffin’s lab on the Florida campus of TSRI, reveals that GlyRS is actually a double agent—in addition to its biologically essential role in making proteins, it can help to further modify proteins in a way that launches cancer growth.

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The researchers found that overexpression of GlyRS may lead to too little p27—a protein than Yang compared to a stop sign for cell growth.

Specifically, the team found that GlyRS creates a protective shield around a modifier protein, called NEDD8, and safely “chaperones” it to meet its target protein, called cullin. With NEDD8 in place, cullin is activated to degrade p27.

Kept at the right levels, p27 regulates the cell cycle, stopping potential cancer growth. But when GlyRS levels increase, too much p27 gets degraded and cells multiply unchecked.

“Cancer cells hijack and over-exaggerate the system,” said TSRI Research Associate Zhongying Mo, first author of the study. “This can lead to tumorigenesis.”

This process is especially dangerous given GlyRS’s additional function in protein synthesis, which supplies cancers with the proteins they need to keep growing. “Ultimately, both functions are linked to cell proliferation and tumorigenesis,” Yang said.

Indeed, when Mo analyzed data from a breast cancer tissue database, she found that patients with increased GlyRS had higher mortality.

Although this research is at the basic stage, the team believes it could guide future cancer diagnostics and therapies. For example, measuring GlyRS may provide a marker to help doctors predict how quickly a patient’s cancer might progress.

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Scripps Research Institute

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Zika vaccine 'works very well' in mice

Zika vaccine ‘works very well’ in mice

By Michelle Roberts
Health editor, BBC News online
  • 28 June 2016
  • From the section Health

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MosquitoesImage copyright
SPL

A single dose of an experimental vaccine can protect mice against the Zika virus, raising renewed hope of a vaccine for humans, say scientists.

The US team say the results, published in Nature, are “striking” and should “galvanise” research efforts.

Tests in humans could begin in months.

But even if these go well, a licensed vaccine for widespread use to protect those at most risk – such as pregnant women – would still be years away, experts advise.

Urgent need

Zika has been spreading across Central and South America and, most recently, Africa.

More than 60 countries and territories now have continuing transmission of the disease, which is carried by mosquitoes.

The virus causes serious birth defects during pregnancy and has been declared a global public health emergency.

Image copyright
AP

Image caption

A baby from Brazil who has microcephaly – a birth defect linked to Zika

Developing a vaccine for pregnant women to protect their unborn babies is an international research priority.

Zika jab

US scientists from the Walter Reed Army Institute of Research, the Beth Israel Deaconess Medical Center and Harvard Medical School tested two types of Zika vaccine in mice – one based on bits of genetic code from the virus and another that is an inactive (and therefore harmless) replica of Zika.

Both worked well, protecting every mouse that was immunised against the virus. In comparison, all of the mice not given the vaccine caught Zika after they were exposed to it.

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The WRAIR says it will push ahead with developing the purified inactivated virus vaccine, because this approach is well chartered ground – there are many existing vaccines for other disease that use this type of technology, whereas there are relatively few DNA-based vaccines.

Future tests will need to check the vaccine is safe and effective in humans, as well as how long the immunity might last.

Researcher Dr Dan Barouch said: “There’s a lot of unknowns.

“With the preclinical demonstration of efficacy of these Zika virus vaccines, then we hope that this news will electrify and galvinise the vaccine effort against Zika virus.”

Other researchers have been testing what effect Zika infection has on the immune system of monkeys.

They have shown that once the animals have recovered from the infection, they have lasting immunity against the disease – at least for the few months the researchers have been able to observe to date.

The University of Wisconsin-Madison researchers say this is good news for vaccine developers.

Lead researcher Prof David O’Connor said: “It suggests the sort of immunity that occurs naturally is sufficient.

“If you can mimic that in a vaccine, you’ll likely have a very successful vaccine.”

But other experts are more cautious.

Prof Jonathan Ball, from the UK’s Nottingham University, said there were potential risks with the vaccine that needed addressing.

“These studies clearly show us that the vaccine is able to generate antibodies that protect the mice from Zika infection,” he said.

“However, it is also possible that the vaccine might produce antibodies that also recognise other viruses from the same family, like Dengue virus for example.

“The real worry is that these cross-reactive antibodies may actually enhance the infection of the other viruses, potentially causing very severe disease.”

Prof Peter Openshaw, from the British Society for Immunology, said it was important to move to human studies as soon as possible.

“By the time human vaccines are ready, many of the vulnerable population will have already been naturally infected,” he said.

“The purpose of vaccination will presumably be to protect travellers and those wishing to become pregnant.

“It will be vital to see how vaccines will work in such situations and how the practical and economic barriers to vaccine deployment can be overcome.”

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