Quicker Sepsis Treatment Saves Lives: Q & A With Sepsis Researcher Christopher Seymour

Sepsis is a serious medical condition caused by an overwhelming immune response to infection. The body’s infection-fighting chemicals trigger widespread inflammation, which can lead to blood clots and leaky blood vessels. As a result, blood flow is impaired, depriving organs of nutrients and oxygen. In severe cases, one or more organs fail. In the worst cases, blood pressure drops, the heart weakens, and the patient spirals toward septic shock. Once this happens, multiple organs—lungs, kidneys, liver—may quickly fail, and the patient can die.

Because sepsis is traditionally hard to diagnose, doctors do not always recognize the condition in its early stages. In the past, it has been unclear how quickly sepsis needs to be diagnosed and treated to provide patients with the best chance of surviving.

Credit: University of Pittsburgh.

Now we may have an answer: A large-scale clinical study, published recently in the New England Journal of Medicine Exit icon, found that for every hour treatment is delayed, the odds of a patient’s survival are reduced by 4 percent. Christopher Seymour Exit icon, assistant professor of critical care and emergency medicine at the University of Pittsburgh, and his team analyzed the medical records of nearly 50,000 sepsis patients at 149 clinical centers to determine whether administering the standard sepsis treatment—antibiotics and intravenously administered fluids—sooner would save more lives.

I spoke with Seymour about his experience treating sepsis patients and his research on the condition, including the new study.

CP: How big a public health problem is sepsis?

CS: Our recent work with the Centers for Disease Control and Prevention suggests there might be as many as 2 million sepsis cases in the United States each year. I can share personally that sepsis, or septic shock, is far and away the most common life-threatening condition that I treat in the ICU (intensive care unit). It’s quite devastating, particularly among our elders, and it requires prompt care. Although the mortality rate may be decreasing, it’s still quite high. About 1 in 10 patients with sepsis don’t survive their hospital stay. Even young, healthy people can succumb from sepsis. And if you’re fortunate to survive, you can have significant problems with cognitive and physical function for many months to years down the line.

Unfortunately, the incidence of sepsis may even be increasing. More patients are surviving serious illnesses that used to be fatal. They’re alive, but their health is compromised, so they are at higher risk for sepsis. Also—and this is a positive—we are seeing greater recognition and increased reporting of sepsis. Both factors probably contribute to the higher numbers of reported sepsis cases.

CP: What are some of the biggest challenges in fighting sepsis?

CS: The first challenge is public awareness. It’s important that the public knows the word sepsis, that they’re familiar with sepsis being a life-threatening condition that results from an infection, and that they know it can strike anyone—young, old, healthy, or sick. But it’s also important to know that not every infection is septic, nor will every cut or abrasion lead to life-threatening organ dysfunction.

Another part of the problem is that sepsis is not as easy for patients to recognize as, say, myocardial infarction (heart attack). When patients clutch their chest in pain, they intuitively recognize what’s happening. Patients frequently don’t recognize that they’re septic. People should know that when they have an infection or take antibiotics as an outpatient, and they’re starting to feel worse or having other new symptoms Exit icon [PDF, 147KB], they may be at risk of sepsis. They should go to the emergency department or seek medical help.

The second challenge in fighting sepsis is that it’s just hard to diagnose, even for well-trained clinicians. Both issues can lead to delays in care, the most important of which is the delay in treatment with antibiotics.

CP: Tell me about your recent clinical trial. What question did you set out to answer?

CS: There’s been a lot of interest in the early recognition and treatment of sepsis over the past decade. Recently, the National Institutes of Health/National Institute of General Medical Sciences funded a large, multicenter trial called ProCESS, which tested various strategies for treating sepsis. This trial told us that a standardized sepsis protocol among people who had already received antibiotics didn’t necessarily change survival rates. But what it left unanswered was the very important question of when the patient first arrives at the emergency department, how fast do we need to provide antibiotics and fluids for the best possible outcome? Continue reading

Having a BLaST in Alaska … and Beyond

Lori Gildehaus and her lovable, mischievous dog, Charley. Credit: Lori Gildehaus.

Lori Gildehaus loves her job because she’s almost always doing something different. Some days, she leads professional development sessions for undergraduate students at the University of Alaska, Fairbanks (UAF). Other days, she’s weathered down in isolated communities along Alaska’s coast while leading community science and outreach events. These activities are just a few of her many responsibilities. Gildehaus is a laboratory research and teaching technician for UAF’s Biomedical Learning and Student Training Exit icon (BLaST) program.

UAF’s BLaST program is one of 10 sites across the country in the Building Infrastructure Leading to Diversity (BUILD) initiative. As a component of the NIH Diversity Program Consortium, BUILD aims to find the best ways to engage and retain students from diverse backgrounds in biomedical research. Each BUILD site is as unique as the community it serves. UAF’s BLaST program embraces Alaska Native culture and the unique landscape that its students, faculty, and staff call home.

UAF attracts students from across Alaska, making for a diverse student body. BLaST serves not only UAF but also seven other campuses throughout Alaska, ranging from IỊisaġvik College in Utqiaġvik (formerly Barrow) at the northern tip of the state, to the University of Alaska Southeast in Sitka, more than 1,000 miles away. In any area that large, it would be difficult to organize community science outreach and foster connections between institutions. But in Alaska, there aren’t even roads connecting most rural campuses to Fairbanks.

Bridging gaps

Gildehaus and BLaST’s four other laboratory research and teaching technicians help bridge these gaps and bring science to local communities. They also serve as intermediaries between undergraduate students doing research and their professors. For undergraduates, talking to professors can be intimidating, and navigating the university landscape can be overwhelming. One of Gildehaus’ responsibilities is providing guidance to students.

“We want undergraduates to have a really good opportunity to explore their interests and have a good experience on their research projects,” Gildehaus says.

Gildehaus has a broad background, including biological sciences, human anatomy and physiology, science outreach, and mentoring. This experience helps her develop BLaST’s mentoring component. BLaST uses a tiered mentoring approach to provide opportunities for undergraduate and graduate students to share experiences and participate in mentoring.

Gildehaus has planned three mentoring workshops for fall 2017. One of these workshops, organized with assistance from the National Research Mentoring Network Exit icon, will focus on culturally aware mentoring. Another will teach attendees how to navigate conversations, share stories, and increase awareness and understanding of Alaska Native and other cultures.

Bringing science outside the lab

BLaST’s diverse group of students includes many people who reside in rural areas and live a subsistence lifestyle. Traditional lab work schedules and science education can often seem disconnected from these communities. To better engage students, BLaST implements the One Health Approach, which emphasizes the interconnectedness between human, animal, and environmental health by promoting ways to expand interdisciplinary collaborations to attain optimal health for all. The program helps students recognize that there are opportunities to be involved in biomedical research in their communities, such as researching the natural vegetation of the Alaskan tundra, studying marine mammals, or finding cures for illnesses.   Continue reading

Fall 2017 Issue of Findings Magazine

It’s back! Check out the new issue of Findings magazine.

Findings presents cutting-edge research from scientists in diverse biomedical fields. The articles are aimed at high school students with the goal of making science—and the people who do it—interesting and exciting, and to inspire young readers to pursue careers in biomedical research. In addition to putting a face on science, Findings offers activities such as quizzes and crossword puzzles and, in its online version, video interviews with scientists.

The Fall 2017 issue profiles Yale University biologist Enrique De La Cruz, who studies how actin—a protein chain that supports cell structure—breaks so easily. Also profiled is University of California, Berkeley, biologist Rebecca Heald and her study of developmental factors that control an animal’s size.

This issue also features:

  • A virtual reality program designed to help burn patients manage pain
  • The promise of gene therapy for glaucoma
  • The many ways scientists categorize the biological world using “omics”
  • What researchers know—and don’t know—about how general anesthetics work
  • How animation helps researchers visualize interactions between biological molecules
  • How cells use sugary outer coatings to distinguish friend from foe
  • What makes our tissues stiff, squishy, solid, or see-through (hint: its initials are ECM)
  • How super-powerful microscopes are revealing views of biology never possible before

View Findings online, or order a print copy (classroom sets of up to 30 copies are available for educators).

 

Engage Students in Science with SEPA-Funded Education Materials

As school starts up again, we look forward to a year that further enhances health and science literacy and brings students closer to pursuing science as an exciting future career. The National Institutes of Health continues to help both educators and students toward these goals through its Science Education Partnership Award (SEPA) Program Exit icon.

What Is SEPA?

SEPA funds innovative science, technology, engineering, and mathematics (STEM), and informal science education (ISE) projects for students in pre-kindergarten through grade 12 (P-12), as well as public outreach activities such as science museum exhibits. Its goal is to invest in educational activities, including interactive online resources, that improve the training of a future workforce to meet the country’s biomedical research needs. SEPA encourages partnerships between biomedical researchers and P-12 teachers, schools, and other interested groups. SEPA provides:

  • Opportunities for students from underserved communities to learn about careers in basic or clinical research.
  • Professional development, skills, and knowledge building for science teachers.
  • Support for science centers and museum exhibits on health and medicine to improve community health literacy.

In March 2017, SEPA found its new home with the National Institute of General Medical Sciences (NIGMS). Congress mandated the move so that SEPA could more efficiently integrate with our other institution-building and research training programs and increase collaboration opportunities between them.

SEPA-Funded Resources

The following are just some of the various SEPA-funded resources that educators can use to engage their students in science:

Spiral of Life Mural Series: Animal Evolution Exit icon. Credit: Duquesne University.

The Partnership in Education: movies, games, and curricula Exit icon (elementary and middle school)

The Partnership in Education at Duquesne University specializes in using cutting-edge technologies and creative media platforms—including videos, apps, posters, and lesson plans—to bring science to life and inspire lifelong learning. Topics include development Exit icon, evolution Exit icon, the science of sleep, and regenerative medicine Exit icon. Continue reading

Protein Alphabet: A Picture Is Worth One Letter

It’s back-to-school time. That means learning lots of new facts and figures. In science, terms tend to be several syllables, sometimes with a Latin word thrown into the mix. As a result, many are referred to by their acronyms, such as DNA—short for deoxyribonucleic acid. This makes them easier both to remember and to say.

Researcher Mark Howarth Exit icon of Oxford University, has taken this a step further. Searching through information stored in the NIGMS-funded Protein Data Bank Exit icon, he curated a 3-D protein alphabet. It’s a set of 26 protein crystal structures that look like they were fashioned from bits of rainbow-colored curly ribbon. This 3-D alphabet helps us see what different protein strands look like, and explains terms and concepts relating to protein structure and function.

Proteins are molecules that play important roles in virtually every activity in the body. They form hair and fingernails, carry oxygen in the blood, enable muscle movement and much more. Although proteins are made of long strands of small molecules called amino acids, they do not remain as a straight chain. Some proteins are composed of multiple amino acid strands that wind together in the completed protein. The strands twist, bend and fold into a specific shape, and the protein’s structure enables it to perform its task. For instance, the “Y” shape of antibodies helps these immune system proteins bind to foreign molecules such as bacteria or viruses while also drawing in other immune system molecules. Continue reading

Happy Birthday, BioBeat

This month, our blog that highlights NIGMS-funded research turns four years old! For each candle, we thought we’d illuminate an aspect of the blog to offer you, our reader, an insider’s view.

Who are we?

Over the years, the editorial team has included onsite science writers, office interns, staff scientists and guest authors from universities. Kathryn, who’s a regular contributor, writes entirely from her home office. Chris, who has a Ph.D. in neuroscience and now manages the blog, used to do research in a lab. Alisa has worked in NIGMS’ Bethesda-based office the longest: 22 years! She and I remember when we first launched Biomedical Beat as an e-newsletter in 2005. You can read more about each of the writers on the contributors page and if you know someone who’s considering a career in science communications, tell them to drop us a line.

How do we come up with the stories?

We get our story ideas from a range of sources. For instance, newspaper articles about an experimental pest control strategy in Florida and California prompted us to write about NIGMS-funded studies exploring the basic science of the technique. A beautiful visual from a grantee’s institution inspired a short post on tissue regeneration research. And an ongoing conversation with NIGMS scientific staff about the important role of research organisms in biological studies sparked the idea for a playful profile of one such science superstar.

A big change in our storytelling has been shifting the focus from a single finding to broader progress in a lab or field. So instead of reporting on a study just published in a scientific journal, we may write about the scientist’s career path or showcase a collection of recent findings in that particular field. These approaches help us demonstrate that scientific understanding usually progresses through the slow and steady work undertaken by many labs.

What are our favorite posts?

I polled the writers on posts they liked, and the list is really long! Here are the top picks.


Four Ways Inheritance Is More Complex Than Mendel Knew


The Endoplasmic Reticulum: Networking in the Cell


Interview With a Scientist: Janet Iwasa, Molecular Animator


From Basic Research to Bioelectric Medicine


An Insider’s Look at Life: Magnified, an Airport Exhibit of Stunning Microscopy Images

What are your favorite posts?

We regularly review data about the number of times a blog post has been viewed to identify the ones that interest readers the most. That information also helps guide our decisions about other topics to feature on the blog. The Cool Image posts are among the most popular! Below are some other chart-topping posts.


Our Complicated Relationship With Viruses


The Proteasome: The Cells Trash Processor in Action


Demystifying General Anesthetics


Meet Sarkis Mazmanian and the Bacteria That Keep Us Healthy


5 Reasons Biologists Love Math

We always like hearing from readers! If there’s a basic biomedical research topic you’d like us to write about, or if you have feedback on a story or the blog in general, please leave your suggestions in the comment field below or email me.

RISE-ing Above: Embracing Physical Disability in the Lab

This is the fourth post in a new series highlighting NIGMS’ efforts toward developing a robust, diverse and well-trained scientific workforce.

Marina Nakhla

Marina Z. Nakhla
Hometown: West Los Angeles, California
Blogs For: Ottobock “Life in Motion,” Exit icon a forum for the amputee community, where she’s covered topics ranging from medical insurance to dating.
Influential Book: The Catcher in the Rye by J.D. Salinger
Favorite TV Show: Grey’s Anatomy
Languages: English and Arabic
Unusal Fact: Gets a new pair of legs every year or two

Nakhla at her graduation from California State University, Northridge, where she graduated with a B.A. in psychology with honors. She is currently a second-year master’s student there studying clinical psychology. Credit: Christina Nakhla.

When Marina Z. Nakhla was just a toddler, she lost both of her legs. Now 22 and a graduate student at California State University, Northridge (CSUN), she has hurdled obstacles most of us never face.

Nakhla conducts research to better understand the decrease in mental abilities experienced by people with brain diseases. She is a scholar in CSUN’s Research Initiative for Scientific Enhancement (RISE) Program. This training program aims to enrich and diversify the pool of future biomedical researchers. Her long-term goal is to earn a Ph.D., to work as a clinical psychologist and to continue conducting research in neuropsychology. Along the way, she aspires to be a leader to her peers and an advocate for underrepresented people, particularly those with disabilities.

I first learned about Nakhla from an email message titled “CSUN RISE Student.” The acronym, pronounced “see [the] sun rise,” is an apt motto for a program that prepares students for a bright future in science. I believe it also encapsulates Nakhla’s positive, forward-looking mindset, despite the obstacles she has faced. Here’s her story:

Q: What got you interested in science?

A: Growing up, I was always drawn to science. I enjoyed learning how things work. I first became interested in psychology after reading The Catcher in the Rye in high school. I was so intrigued by Holden Caulfield’s thought processes and experiences of alienation and depression, despite the fact that he came from a wealthy family and went to a good school.

Why are some people more prone to experiencing depression? Why are some peoples’ thought processes so different than others? What factors contribute to resiliency? How can we help these people? These questions also made me think about the significant adversities that I had personally experienced. My desire to know more about the brain, as well as my personal experiences, instilled my passion to make a difference in others’ lives through science. Continue reading

Cool Image: Biological Bubbles

Cells are in the process of pinching off parts of their membranes to produce bubbles filled with a mix of proteins and RNAs. Researchers are harnessing this process to develop better drug delivery techniques. The image, courtesy of Chi Zhao, David Busch, Connor Vershel and Jeanne Stachowiak of the University of Texas at Austin, was entered in the Biophysical Society’s 2017 Art of Science Image contest and featured on the NIH Director’s Blog.

This fiery-looking image shows animal cells caught in the act of making bubbles, or blebbing.

Certain cells regularly pinch off parts of their membranes to produce bubbles filled with a mix of proteins and RNAs. The green and yellow portions in the image show the cell membranes as they separate from the cell’s skeleton and bleb from the main cell. The bubbles, shown in red, are called plasma-derived membrane vesicles, or PMVs. PMVs can travel to other parts of the body where they may aid in cell-to-cell communication.

The University of Texas at Austin researchers who produced this image are exploring ways to use PMVs to deliver medicines to precise locations in the body.

Blebbing for Drug Delivery

Drug delivery research tries to find ways to carry medicines to only the tissues in the body that need them with the goal of reducing side effects. To achieve this, delivery methods need to recognize just the cells they target, usually by finding a unique protein on the cell’s surface. Scientists can make proteins that recognize and attach to targets such as cancer cells, but they’ve had trouble attaching medicines to the proteins they made. To get around this problem, scientists could employ PMV-making cells in a laboratory, perhaps even cells taken from a patient who is receiving treatment. They could engineer the cells to make the targeting proteins and then attach the targeting proteins to the PMV surface. The cell’s own protein-making machinery does the hardest job.

The Texas scientists have engineered such donor cells with proteins on their surfaces that precisely target certain kinds of breast cancer cells. When the donor cells are induced to bleb, they produce PMVs laden with the target proteins that locate and bind to the cancer cells.

Researchers hope that eventually PMVs with surface targeting proteins could be filled with medicines and infused into the patient to deliver the drugs specifically to cancerous cells while leaving healthy tissues untouched. Research will continue to investigate this possibility.

This research was funded in part by NIH under grant R01GM112065.

Viruses: Manufacturing Tycoons?

Pseudomonas chlororaphis

A computer image shows a bacterial cell invaded by a virus. The virus uses the cell to copy itself many times. It has built a protein compartment (red, rough circle surrounding the center) to house its DNA. Viral heads (blue, smaller pentagonal shapes spread through out) and tails (pink, rod shaped near the edges) are essential parts of a finished viral particle. The small, light blue particles are the bacterium’s own protein-making ribosomes. Credit: Vorrapon Chaikeeratisak, Kanika Khanna, Axel Brilot and Katrina Nguyen.

As inventors and factory owners learned during the Industrial Revolution, the best way to manufacture a lot of products is with an assembly line that follows a set of precisely organized steps employing many copies of identical and interchangeable parts. Some viruses are among life’s original mass producers: They use sophisticated organization principles to turn bacterial cells into virus particle factories.

Scientists at the University of California, San Diego, and the University of California, San Francisco, used cutting-edge techniques to watch a bacteria-infecting virus (bacteriophage) set up its particle-making factory inside a host cell.

The image above shows this happening inside a Pseudomonas chlororaphis, a soil-borne bacterium that protects plants against fungal pathogens. The virus builds a compartment (red, rough circle surrounding the center) that helps organize an assembly line for making copies of itself. The compartment looks like a cell nucleus, which bacteria do not have, and it functions like a nucleus by keeping activities that directly involve DNA separate from other cellular functions. Continue reading

Chasing Fireflies—and Better Cellular Imaging Techniques

firefly
Firefly. Credit: Stock photo.

The yellow-green glow from this summer’s fireflies teased my kids across the yard. Max and Stella zigzagged the grass, occasionally jumping into the air to cup a firefly in their hands and then proudly shouting, “I got one!”

Chasing fireflies on a summer night is a childhood rite of passage for many, including Nathan Shaner who grew up in New Jersey. “It was one of my favorite things about summer,” he recalls. “I’d catch them with my hands—I’d never jar them.”

Today, Shaner studies the science of bioluminescence, which gives fireflies and many other organisms the natural ability to emit light. His goal is to make bright bioluminescent tags that he and other scientists can use to study living cells in greater detail. “There’s this very beautiful thing that evolved in nature, and we can use it to enable new discoveries,” he says.

Thousands of organisms glow as a way to communicate, spook predators, lure prey or attract mates. There are a few terrestial examples, such as fireflies, glowworm insect larvae and foxfire fungi, and many more acquatic ones, including types of marine plankton, fish, jellyfish, shrimp, squid and sea urchins. One research team estimated nearly three quarters of sea life have bioluminescent capabilities.

Bioluminescence is common across the tree of life (left to right): Panellus Stipticus (foxfire fungi); Lampryis noctiluca (glowworm insect); Aurelia Aurita (moon jellyfish). Credit: Wikimedia Commons, Ylem; Wikimedia Commons, Wofl; stock photo.

Every studied case of bioluminescence involves oxygen, a light-emitting pigment called luciferin and a protein called luciferase. Luciferase encourages the pigment’s reaction with oxygen, releasing energy in the form of light. Although many bioluminescent creatures have their own form of luciferase, they share just a handful of luciferins. For example, the luciferin called coelenterazine is found in many aquatic organisms. Continue reading