jueves, 20 de julio de 2017

Please Watch Our Grand Rounds Encore Session and our New Beyond the Data: “E-cigarettes: An Emerging Public Health Challenge”

Public Health Grand Rounds | CDC

Public Health Grand Rounds

In Case You Missed It:
CDC’s Public Health Grand Rounds Presents the Encore Session:
“E-cigarettes: An Emerging Public Health Challenge”
View this encore session and our newly updated Beyond the Data segmenthere.
This session was originally presented on October 20, 2015.

Presented By:

Brian King, PhD, MPH
Deputy Director for Research Translation
Office on Smoking and Health
National Center for Chronic Disease Prevention and Health Promotion, CDC
“Patterns of E-cigarette Use Among U.S. Adults and Youth” 

Jonathan M. Samet, MD, MS Distinguished Professor and Flora L. Thornton Chair
Department of Preventive Medicine
Keck School of Medicine, University of Southern California
“Health Consequences of Electronic Cigarettes”

John Wiesman, DrPH, MPH Secretary of Health
Washington State Department of Health
“E-cigarettes in Washington State: On the Front Lines”

Matthew L. Myers
President Campaign for Tobacco-Free Kids
“Attaining a Tobacco-Free Generation and the Emergence of E-cigarettes”
Facilitated By:

John Iskander, MD, MPH, Scientific Director, Public Health Grand Rounds
Phoebe Thorpe, MD, MPH, Deputy Scientific Director, Public Health Grand Rounds
Susan Laird, MSN, RN, Communications Director, Public Health Grand Rounds

For questions about this Grand Rounds topic: Feel free to e-mail your questions. 

Heart health and air quality: What’s the connection?

Million Hearts e-Update

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The Science of Million Hearts®


Air quality as a risk factor for heart attack?

It may sound strange, but worsening air quality puts people at risk for heart attacks and other cardiovascular (CV) conditions, especially among people who are already vulnerable. More than 1.5 million people in the United States suffer from heart attacks and strokes each year. Millions more have high blood pressure or heart rhythm disorders, putting this priority population especially at risk from particle pollution’s effects.
Million Hearts® is dedicated to driving implementation of evidence-based public health and clinical strategies that help prevent CV events. With that in mind, we recently launched a webpage to spread awareness about particle pollution and CV health, with resources to help track local air quality. Use the resources in this newsletter to learn about the connection between heart health and particle pollution to help keep people healthy this summer and beyond.
—Janet Wright, MD, FACC Executive Director, Million Hearts®

Do This!

Share the EPA Air Quality Index with networks and people at risk.    
Particle pollution puts people with CV conditions at higher risk for heart problems or stroke. Post this tool on your websites and social media so people can check air quality before they go outside for physical activity. Those at risk should avoid going outside on days ranked “orange” or worse and instead choose indoor versions of their favorite activities.

Quick Fact

One in three American adultshas heart or blood vessel disease and is at higher risk from air pollution, which can trigger heart attacks and strokes and arrhythmias.

NIH-Supported Scientists Elicit Broadly Neutralizing Antibodies to HIV in Calves | NIH: National Institute of Allergy and Infectious Diseases

NIH-Supported Scientists Elicit Broadly Neutralizing Antibodies to HIV in Calves | NIH: National Institute of Allergy and Infectious Diseases

NIH: National Institute of Allergy and Infectious Diseases

NIH-Supported Scientists Elicit Broadly Neutralizing Antibodies to HIV in Calves

Unique Structure of Bovine bNAbs May Inform HIV Vaccine, Therapeutics Design
July 20, 2017
Scientists supported by the National Institutes of Health have achieved a significant step forward, eliciting broadly neutralizing antibodies (bNAbs) to HIV by immunizing calves. The findings offer insights for HIV vaccine design, and support further study of modified bovine antibodies as HIV therapeutics or prevention tools in humans, scientists reported in a paper published online today in Nature.
Researchers have observed that about 10 to 20 percent of people living with HIV naturally develop bNAbs to the virus, but usually only after about two years of infection. These bNAbs have been shown in the laboratory to stop most HIV strains from infecting human cells, and to protect animal models from infection.  However, scientists have so far been unsuccessful in prompting the human immune system to produce bNAbs through immunization. Further, while bNAbs isolated from people with HIV infection have demonstrated promise in primate studies and have entered human studies for HIV prevention and treatment, questions remain about whether effective antibodies could be produced rapidly and at a scale suitable for widespread distribution.
Cattle may offer some help solving these problems, report researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, at the Scripps Research Institute (TSRI), the International AIDS Vaccine Initiative (IAVI) and Texas A&M University. While cattle do not naturally acquire the human virus HIV, their immune systems have unique features that the researchers thought would allow them to produce potent antibodies when injected with HIV immunogens, or proteins designed to mimic proteins on the surface of HIV. 
In their study, the researchers injected HIV immunogens into the flanks of four calves and waited for their immune systems to respond. All four cows developed bNAbs to HIV in their blood as rapidly as 35 to 50 days following two injections. This immunogen—a BG505 SOSIP trimer—can elicit HIV bNAb responses consistently and rapidly.
While bovine bNAbs are not likely suitable for clinical use in humans in their current form, exploring this rapid production may help answer important research questions.
“From the early days of the epidemic, we have recognized that HIV is very good at evading immunity, so exceptional immune systems that naturally produce broadly neutralizing antibodies to HIV are of great interest—whether they belong to humans or cattle,” said Anthony S. Fauci, M.D., NIAID Director.
The TRSI investigators isolated specific antibodies from the immunized calves to study their properties. One of these antibodies is particularly potent, and binds to a key site that HIV uses to attach to and infect immune cells. Called NC-Cow 1, it neutralized about two-thirds of a panel of diverse HIV isolates. This activity is somewhat similar to bNAbs isolated from humans, such as VRC01, an agent currently in clinical trials as an HIV prevention tool that neutralizes 90 percent of HIV strains but is less potent.
“A minority of people living with HIV produce bNAbs, but only after a significant period of infection, at which point virus in their body has already evolved to resist these defenses,” said Dennis R. Burton, Ph.D., a lead author on the study, director of the NIH’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery and scientific director of the IAVI Neutralizing Antibody Consortium at TSRI. “The potent responses in this study are remarkable because cattle seem to produce bNAbs in a relatively short amount of time. Unlike human antibodies, cattle antibodies are more likely to bear unique features and gain an edge over complicated HIV immunogens.”
HIV researchers previously discovered that bNAbs isolated from people living with HIV for many years tend to have longer versions of a looped region called HCDR3. These extended loops help to penetrate sugar molecules on the surface of HIV, enabling the high performing antibodies to reach and recognize concealed regions of HIV proteins and neutralize the virus.  In previous experiments, the TSRI team and their collaborators observed that cattle produce antibodies with long HCDR3 loops at a much higher frequency than humans, that these HCDR3 loops are ultra-long, and that bovine immune cells may produce antibodies with effective immunogen binding through a fundamentally different mechanism than takes place in human immune cells.  The researchers note that a promising approach to HIV vaccine development may be to promote the human immune system’s development of long HCDR3 loops.
While no one knows definitively why these powerful antibodies evolved in cattle, one theory holds that the long HCDR3 loops are tied to the animals’ extensive gastrointestinal systems. Cattle and other ruminant animals have multi-chambered stomachs and a robust population of bacteria in their digestive tracts to help break down a diet of tough grasses. However, these bacteria can pose an infection risk if they escape the gut, so cattle with a versatile mechanism for producing potent antibodies would greatly benefit from the increased protection. Further study on how this mechanism contributed to the elicitation of bNAbs to HIV in cattle may inspire novel approaches to HIV vaccine development. 
“HIV is a human virus,” said Devin Sok, a study leader and Antibody Discovery and Development Director at IAVI, “but researchers can certainly learn from immune responses across the animal kingdom.”
Researchers may also explore mimicking or modifying the potent isolated bNAb or those like it to develop experimental antibody-based HIV therapeutics and prevention tools, as well as treatments for other pathogens that have evolved to avoid human antibody responses. The pharmaceutical industry already uses cattle and other animals associated with agriculture, such as chickens and pigs, to produce antibody therapeutics and prophylactics, immunogens for vaccines and therapeutic hormones. Because the current research indicates that the bovine immune system may typically work quickly to produce effective antibodies against difficult pathogens such as HIV, immunizing cattle and discovering such antibodies may become a useful approach to ensure these tools are readily accessible.
Reference:  D Sok et alRapid elicitation of broadly neutralizing antibodies to HIV by immunization in cowsNature DOI: 10.1038/nature23301 (2017).

Our Complicated Relationship With Viruses | Biomedical Beat Blog - National Institute of General Medical Sciences

Our Complicated Relationship With Viruses | Biomedical Beat Blog - National Institute of General Medical Sciences

Biomedical Beat Blog – National Institute of General Medical Sciences

Our Complicated Relationship With Viruses

Illustration of Influenza Virus H1N1. Swine Flu.
Nearly 10 percent of the human genome is derived from the genes of viruses. Credit: Stock image.
When viruses infect us, they can embed small chunks of their genetic material in our DNA. Although infrequent, the incorporation of this material into the human genome has been occurring for millions of years. As a result of this ongoing process, viral genetic material comprises nearly 10 percent of the modern human genome. Over time, the vast majority of viral invaders populating our genome have mutated to the point that they no longer lead to active infections. But they are not entirely dormant.
Sometimes, these stowaway sequences of viral genes, called “endogenous retroviruses” (ERVs), can contribute to the onset of diseases such as cancer. They can also make their hosts susceptible to infections from other viruses. However, scientists have identified numerous cases of viral hitchhikers bestowing crucial benefits to their human hosts—from protection against disease to shaping important aspects of human evolution, such as the ability to digest starch.
Protecting Against Disease
Geneticists Cedric Feschotte Exit iconEdward Chuong Exit icon and Nels Elde Exit icon at the University of Utah have discovered that ERVs lodged in the human genome can jump start the immune system.
For a virus to successfully make copies of itself inside a host cell, it needs molecular tools similar to the ones its host normally uses to translate genes into proteins. As a result, viruses have tools meticulously shaped by evolution to commandeer the protein-producing machinery of human cells.
Invaders in your DNA infographic
View larger image Exit icon. Credit: Cedric Feschotte and Nels Elde, University of Utah.
Feschotte and his team recognized that because viruses tend to attack the immune system, they may be particularly adept at manipulating immune system genes. Ancient human genomes may have evolved in response. Feschotte believes it is possible that the genomes of humans (or our ancient ancestors) repurposed viral DNA for their own defense, using it to spur the immune system into action against viruses and other foreign invaders.
“We hypothesized that these ERVs were likely to be primary players in regulating immune activity because viruses themselves evolved to hijack the machinery to control immune cells,” says Feschotte.
To investigate their hypothesis, Feschotte and his team used a gene-editing technique called CRISPR to systematically eliminate individual ERV sequences in human cells. After removing one of the sequences, the researchers observed a notable weakening of immune function when the cells were challenged by viral infection. The removal of three other ERV sequences also compromised the immune response.
These findings suggest that each of these ERV elements can activate different gene components of the immune system. The team believes there are thousands more ERV sequences with similar regulatory activities, and it hopes to explore them systematically in future studies.
“We think we’ve only scratched the surface here on the regulatory potential of ERVs,” says Feschotte.
Underscoring the complicated relationship humans have with viruses, strong evidence also exists that in some cases ERVs cause cancer but in other cases they protect against cancer. For example, an ERV called ERV9 can detect cancer-related damage in the DNA of cells in the testis. ERV9 then prompts a neighboring gene to induce the damaged cells to commit suicide. This protective mechanism ensures that the cancer cells will not spread.
Shaping Human Evolution
Scientists have also discovered that viral intruders have driven the evolution of human physiological functions ranging from early development to digestion.
Nearly 20 years ago, scientists identified an ERV-derived gene called syncytin that appears to play a key role in the development of the human placenta. Syncytin originated from a retroviral gene encoding a protein that is embedded in the outer surface of a virus. This protein mediates the fusion of the virions with the host cell membrane, thereby facilitating viral infection. In a remarkable turn of events, the human body has repurposed the viral protein’s cell-fusing activities to promote the formation of the layer of cells that merge the placenta and the uterus.
Scientists have also found that viral invaders are critical to humans’ ability to digest starch. The insertion of an ERV near the human pancreatic gene for making amylase—a protein that helps humans digest carbohydrates—led to the expression of amylase in saliva. The consequent ability to digest starch in the mouth has had profound effects on the human diet, notably a shift toward eating foods like rice and wheat. By helping to kick start digestion in the mouth, amylase relieves some of the burden of breaking down food faced by the small intestine. If this critical enzyme were not excreted in saliva, the small intestine would have more difficulty metabolizing sugars and starches.
More recently, in 2016, a team of U.S. and Israeli researchers reported that a common strategy that host organisms use for nullifying viruses—bombarding them with mutations—has helped shape human evolution.
APOBEC enzyme structure.
APOBEC enzyme structure. Credit: Wikimedia Commons, Justin Steinfeld.
The researchers, led by computational biologist Alon Keinan Exit icon of Cornell University, in collaboration with Erez Levanon Exit icon from Bar-Ilan University, study a virus-fighting family of human enzymes called APOBECs. During periods when DNA unzips into two single strands—when it has been damaged, is in the process of being copied, or is being transcribed into RNA—the APOBEC enzymes seek out bits of viral DNA. They then systematically strafe the viral DNA—typically swapping many instances of one DNA base for another—in order to neutralize pathogens lurking within the host genome.
How APOBECs Work inforgraphic
View larger image. Credit: Cancer Research UK.
It’s likely that this APOBEC mechanism has also mutated non-viral portions of the human genome. Keinan says the majority of these genetic changes would have done enough damage to cause disease. For the most part, such mutations have been weeded out of the population because they were harmful to survival and reproduction. However, researchers have increasingly linked APOBECs to various cancers.
Keinan’s team has shown that these mutations are also occurring in cells that develop into sperm and eggs and so they are inherited by future generations. And not all of the mutations have been detrimental. The genetic changes that survived through evolutionary time—the ones that did not lead to disease—are more likely to be beneficial. This insight suggests that the APOBEC anti-viral mechanism has helped shape primate evolution through a variety of yet-to-be-identified beneficial mutations. Keinan’s team has reported tens of thousands of such mutations in hominid genomes and is now searching for specific examples that led to changes in function that have contributed to human evolution.
While the search for additional examples of beneficial ERVs and antiviral mechanisms continues, scientists are learning more about viral trespassers with the help of large databases of genomic information from numerous species. They’re trying to figure out how viral DNA integrates into host genomes, how ERVs can jump from one host species to another and how to protect people in the case of these rare, but occasionally deadly, events.
This work was funded in part by NIH under grants R01GM114514R01GM112972R01GM059290, and R01GM108805.
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Interview With a Scientist: Namandjé Bumpus, Drug Metabolism Maven | Biomedical Beat Blog - National Institute of General Medical Sciences

Interview With a Scientist: Namandjé Bumpus, Drug Metabolism Maven | Biomedical Beat Blog - National Institute of General Medical Sciences

Biomedical Beat Blog – National Institute of General Medical Sciences

Interview With a Scientist: Namandjé Bumpus, Drug Metabolism Maven

Medications are designed to treat diseases and make us healthier. But our bodies don’t know that. To them, medications are merely foreign molecules that need to be removed.
Before our bodies can get rid of these drug molecules, enzymes in the liver do the chemical work of preparing the molecules for removal. There are hundreds of different versions of these drug-processing enzymes. Some versions work quickly, others work slowly. In some cases, the versions you have determine how well a medication works for you, and whether you experience side effects from it.
Namandjé Bumpus Exit icon, a researcher at Johns Hopkins University School of Medicine, is interested in how human bodies respond to HIV medications. She studies the enzymes that process these drugs. Her research team discovered that a genetic variant of a liver enzyme impacts the way some people handle a particular HIV drug. This variant is found in around 80 percent of people of European descent. She describes her work in this video.
Bumpus recently presented her research to a more scientifically advanced audience at an Early Career Investigator Lecture at the National Institutes of Health. Watch her talk titled Drug Metabolism, Pharmacogenetics and the Quest to Personalize HIV Treatment and Prevention.
Dr. Bumpus’ work is supported in part by NIGMS grant R01GM103853.