From the flower on your front porch to your cousin’s lower back tattoo, butterflies are one of the most immediately recognizable insects due to their magnificent wings. Though I am no butterfly expert myself, I can distinguish a few species native to my area by their color patterns. Interestingly, wing patterns and coloration may be important for speciation and adaptation to environmental stimuli, as in the case of the peppered moth.

During the Industrial Revolution, evolutionary biologists recognized that black peppered moths were much more common in smog-covered environments, while mostly white peppered moths were found in clean, less polluted environments. This was because the black moths were better camouflaged on smog-covered trees, while the white moths were easily picked off by predators. On clean backgrounds, the opposite was true. Today, the peppered moth serves as a textbook example of Darwinian evolution

What the Painted Lady Can Tell Us About RNA

Patterns help butterflies blend into their environment to escape predators.

click to enlarge

The importance of butterfly wings for survival is clear, but little is currently known about what controls wing patterns. Scientists at Cornell University recently published a study trying to delve into this issue using new molecular biology techniques. Using the Painted Lady butterfly, V. cardui, as a model system, Zhang and colleagues identified genes that were differentially regulated during pupal development using RNA sequencing. RNA sequencing (RNA-seq), unlike DNA sequencing, is a dynamic method used to quantify and compare changes in gene expression by monitoring the level of certain RNAs within cells as they fluctuate to respond to the needs of different environments and developmental stages.

The difficulty lies in teasing out the expression differences that are relevant to the phenotype of interest. Zhang et al. performed RNA sequencing at different stages of pupal development, when the wings are formed, to identify genes that are differentially expressed as candidates for playing a role in wing coloration and patterning. Some of the genes they found seemed especially promising due to previous studies that had already associated them with the development of pigment in other species and were aptly named after colors, including yellow, pale, ebony and black. Altogether, they isolated 27 genes as candidates for controlling

Zhang et al. performed RNA sequencing at different stages of pupal development, when the wings are formed, to identify genes that are differentially expressed as candidates for playing a role in wing coloration and patterning. Some of the genes they found seemed especially promising due to previous studies that had already associated them with the development of pigment in other species and were aptly named after colors, including yellow, pale, ebony and black. Altogether, they isolated 27 genes as candidates for controlling development of the pigment melanin in V. cardui.

Gene Editing to Narrow Down the Possibilities

The authors then used the new gene editing technology, CRISPR-Cas9, to knock out, or inactivate, some of their candidate genes. By creating mutants with different genes inactivated, the authors were able to discern what the genes normally do during wing color development. One mutant, in which the pale gene was knocked out, showed severe defects, including abnormal wing shape and body scales, along with wing color changing from brown to white with a loss of eyespot pigmentation. Other mutants showed similarly striking phenotypes, including hyperpigmentation, abnormal patterning and some pupal lethality. These knockouts helped to confirm that the candidate genes play a role in melanin production and pattern formation in butterfly wings.

The use of RNA sequencing with CRISPR gene editing may prove extremely valuable not only for understanding the genetic basis of melanin formation in butterflies, but also for biomedical researchers. RNA sequencing is rarely used a primary diagnostic tool but recently has been used when other genome sequencing methods fail to explain the cause of undiagnosed genetic diseases. Functional validation using CRISPR gene editing can help to confirm RNA-seq results and provide further proof of the candidate variant’s impact on patients. Zhang’s method may have a butterfly effect, if you will, for many researchers.

References:
Zhang et al., 2017 Genetics 
Cummings et al., 2016 BioRXiV 


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Sarah Robbins

Sarah Robbins is a human genetics Ph.D. student. Her skill at reading recipes has made her able to translate her talents from pies to PCR.

Of the greatest miracles performed by Christ was his healing of lepers, the blind and the deaf. Gregor Mendel, a monk, was the father of modern genetics. Christian missionaries like Mother Teresa saved thousands of people in the name of God. The Christian faith and the art of healing have been connected for centuries, and Christianity continues to strongly influence many medical providers today.

Ancient Christian art adorns the Hagia Sophia in Istanbul, a church that has occupied christian and muslims alike. Image courtesy Rabia Karani

Ancient Christian art adorns the Hagia Sophia in Istanbul, a church that has been occupied by Christian and Muslims alike.
Image courtesy Rabia Karani

A recent conference at Johns Hopkins, the Symposium on Christian Faith, Reason, and Vocation, brought to light many of the ways religion and medicine are intertwined in the lives of modern medical professionals. More specifically, the symposium hosted a panel on faith in medicine featuring providers from around Johns Hopkins. It was moderated by Stephanie Wang, a fourth-year medical student at Johns Hopkins.

At the symposium, providers discussed the ways in which faith was expressed in the workplace. From praying silently in the workplace to discussing faith-based topics with patients, providers covered the spectrum regarding religion in the workplace. David Madder, a primary care provider at Johns Hopkins, discussed how his faith encouraged him to view all people as made in the image of God and how that encouraged his treatment of his patients. Danielle Patterson, a histotechnologist, talked about how the “pathology lab is very open about accepting of you and your religion,” and how prayer with a few of her colleagues in the pathology lab was a regular part of her morning routine prior to heading to work.

quote: Medicine is raw and real, and it involves caring for those whom society has often shunned. For most providers, faith also played a pivotal in the selection of health care as a career. The importance of serving others is a common theme among major religions, and Christianity is full of the deeds of those who chose to help others. According to Nancy Schoenborn, a geriatrician at Johns Hopkins, she sees medicine as a “calling that I am called to serve, and that is why I go the extra mile to do that extra stuff [for my patients].” Another provider, Angel Byrd, a fellow in the Department of Dermatology, discussed how her desire to go into medicine came from witnessing her mother’s career as a social worker and seeing the impact her mother had on the mental health of her clients. Byrd eventually developed an interest in serving those who needed to be cared for and “asked God to help me unfold the path that is right for me every step of the way.”

Faith also serves as a day-to-day guide for many providers and is pervasive in every aspect of their life. Along with guiding some providers on patient management, faith also serves as a sort of solace. Medicine is raw and real, and it involves caring for those whom society has often shunned. Medicine also lends itself to continuous failure to improve the health of patients and involves being physically active for long hours. According to Schoenborn, “There’s a lot we can’t do in medicine, and there’s a lot we don’t know in science, and in those moments, my faith is very important to me to remember that I don’t share that burden alone.” Madder discussed the importance of drawing from within oneself the love of Christ and the importance of spreading this love in the workplace.

quote: "There’s a lot we can’t do in medicine, and there’s a lot we don’t know in science, and in those moments, my faith is very important to me to remember that I don’t share that burden alone.”

The symposium was ultimately a small snapshot of the ways in which Christianity and modern medicine engage with each other. The art of healing is complex and very human, and in such a human enterprise, it is expected for faith to play at least some role in the lives of both practitioners and patients. Schoenborn beautifully summarizes what the Christian faith means to many health care providers: “There are tough times in medicine, but there is also incredible joy and incredible purpose. It is a privilege to be made by God in a certain way and to have those gifts by God to be able to serve his people, mirroring that Jesus was a healer and that we are following in his footsteps.”


About this series:

Although medicine is often seen as a field that is distinct from religion, religious beliefs have a significant impact on the way physicians and medical students approach their training, interactions with patients, and understandings of disease and death. Biomedical Odyssey bloggers Rabia Karani and Stephanie Zuo have created a short blog series on faith and medicine to give you a glimpse into the worlds of Johns Hopkins students who have been influenced strongly by and/or are actively practicing their faiths. 

We hope that you come away with a deeper understanding of the profound impact and immense strength that arises when peoples of faith seek to do good work in the medical field with all their hearts, minds and souls.


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Rabia Karani

Rabia Karani just completed her M.P.H., and is now finishing up her last year of medical school. She is passionate about any topic regarding patient care and public health. An anthropologist at heart, she is an avid reader, a Harry Potter enthusiast, and she hopes to use her love for writing to inspire understanding between different groups of people.

Regenerative medicine has been dubbed the vanguard of 21st-century health care. This emerging field places an emphasis on curing rather than treating injured or impaired tissues, and seeks to repair damaged tissues in vivo (in the living body) using techniques that trigger cells’ intrinsic healing ability. In the event that the body is unable to heal itself, scientists can grow new tissues and organs in the lab using regenerative methods and subsequently implant them safely in the body.

Although previously considered radical, the basic concept of introducing live cells into tissues or the bloodstream relies on old technology dating back to the 1950s. Now, with advances in research techniques and tissue engineering, the elusive goal of regenerative tissues on demand seems within reach. Enter the mesenchymal stem cell, which has emerged as the sentinel conductor of the regenerative apparatus.

What Are Mesenchymal Stem Cells (MSCs)?

They are specialized cells, originally named for their unique ability to morph into any other type of cell in the body. They can be found in every tissue and particularly reside adjacent to blood vessels. At this stage, they go by a peculiar name: pericytes. When tissue injury occurs, blood vessels break down and release pericytes. The detached pericytes have specialized sensors that allow them to pick up on changes in the microenvironment of the injury site. MSCs then secrete factors, which stimulate injury repair and growth of replacement cells.

The Body’s Own Emergency Response Team

This fascinating modus operandi of MSCs is better encapsulated by a real-world analogy. Imagine the scene of a major fire outbreak. Rescue personnel — the fire service, paramedics and emergency rescue workers — are summoned to the scene. They put out the fire, rescue and stabilize survivors, survey the field, intervene to mitigate any further damage, clean up residual debris and create a safe space for survivors, who may then be sent to the emergency room for further care.

Did you know: when an injury occurs, MSCs make growth factors that promote angiogenesis - formation of new blood supply - block cell death, stimulate the replacement of dead cells and prevent scar formation. This search-and-rescue system is recapitulated beautifully by MSCs. When an injury occurs, MSCs release a protective film that blocks an overly aggressive immune reaction and make growth factors that promote angiogenesis — formation of new blood supply — block cell death, stimulate the replacement of dead cells and prevent scar formation. If MSCs sense bacteria, they secrete powerful natural antibiotics that kill the bacteria on contact. Some MSCs migrate into the wound itself and morph to replace the old cells. Being quintessential multitaskers, MSCs stabilize the injured tissue, detoxify it and set up the wound for regenerative repair in a complex, multistage process. MSCs also have the unique ability to distinguish foreign material and are able to sequester cell debris from the site of injury.

According to Arnold Caplan, an expert in the field of MSC biology, who originally coined the term MSC, “These cells are so good at what they do. They are like nature’s own repair mechanics or, if you will, natural drugstores.” Caplan has proposed renaming MSCs as medicinal signaling cells. On Feb. 17, 2017, I heard him speak in Broomsfield, Colorado, at the Annual Conference of the Interventional Orthopedics Foundation (IOF), with the theme “Raising the Bar in Interventional Regenerative Medicine.” The IOF provided grants for residents and trainees to participate in the conference, and I was fortunate to be one of the grant recipients. The meeting highlighted major regulatory hurdles in creating and using combination stem cell-based tissue and gene therapies.

Regenerative Medicine Faces Funding Challenges

In the interest of public safety, the Food and Drug Administration’s Public Health Safety Act controls the licensing of biologic products and imposes strict regulations requiring researchers to submit an investigational new drug application to the FDA before studies in human subjects can be initiated. The FDA raise questions about the purity, potency, safety and use of these cell-based therapies, including MSCs, in humans. Currently, products like platelet-rich plasma, cord blood, allogenic fibroblasts and other regenerative products have gained FDA approval for various clinical indications.

quote: Although the industry has a potential $500 billion economic impact in annual revenues, most investments have come from the private sector. The disparity in funding could hamper fundamental research that is necessary to advance knowledge in the field.However, according to the Department of Health and Human Services, one of the biggest challenges is the lack of cohesive, government-driven funding for regenerative medicine. Although the industry has a potential $500 billion economic impact in annual revenues, most investments have come from the private sector. The disparity in funding could hamper fundamental research that is necessary to advance knowledge in the field. At present, researchers work in isolation, and there are few cross-disciplinary research collaborations. While large-scale trials are needed, these are expensive for private companies to conduct, and the shifting landscape of regulatory requirements often leads to confusion about expectations and acceptable uses of these products.

From a global perspective, some countries, like Britain, Germany, Sweden, Japan, China and Australia, have started their own national initiatives in anticipation of making regenerative medicine a reality. To achieve the promise of MSCs and other cell- and tissue-based therapies in the United States, a more proactive federal initiative is needed. As research in the field continues to evolve, it remains evident that understanding how MSCs interact with each other and connect with blood vessels will be key to mass-producing, preserving and engineering tissue and organ-based therapies in the future.


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Charles Odonkor

Charles Odonkor is a resident in physiatry (physical medicine and rehabilitation) and an Armstrong Institute fellow. An old soul and a dreamer, he is awed by the sacred and explores the world via the lens of a rich Afropolitan heritage.

Traditionally, medical school is viewed as a continuous four-year educational experience. In reality, the structure of medical education is that of contrasting, dichotomous learning methodologies divided into two sequential stages: preclinical and clinical years. The daily lifestyles, schedules and learning styles of medical students within these two distinct but complementary components of medical school could not be more different, and the transition between them is a time of excitement, anxiety and realization.

quote: sometimes, it seems, experts can forget how to return to square one and lay out the basics for students who are seeing a disease for the first time. - Benjamin OstranderBefore this momentous transition, students learn predominantly from lectures accompanied by slides in the classroom. This is supplemented by small-group learning activities. At the Johns Hopkins University School of Medicine, we have the privilege of having teachers who are expert clinicians and often leaders in their fields. With this expertise comes the complexity and attention to detail that is expected from an individual who has dedicated his or her life to understanding a specific topic or disease. Many of our professors are fantastic at conveying this complexity with skill and thoughtfulness. Yet occasionally, the details are lost on medical students, who seek a broader introductory view of a topic and a foundation from which to build upon. Sometimes, it seems, experts can forget how to return to square one and lay out the basics for students who are seeing a disease for the first time. Learners require a strong overarching framework and a grasp of the vocabulary before grappling with intricacies.

Paradoxically, teaching prowess is not something that is required to become a medical professor. The academic hierarchy in medicine is formed by clinical skill, academic productivity and scientific accomplishment. Master clinicians may be genius diagnosticians and empathic caretakers, but this does not also guarantee they will be great teachers. To muddy the waters even further, teaching is not something that is well-compensated or highly rewarded in academic medicine. Teaching takes time and effort, and does not generate revenue. Finally, the best clinicians and most highly respected teachers are most often promoted to administrative roles, where they have significantly less time to see patients and teach the next generation.

A New Model of Teaching Recognition

Another essential component of preclinical education involves peer-to-peer teaching. Fortunately, there are a number of forces countering these issues with the structure of medical education. Last spring, the Distinguished Teaching Society of the Johns Hopkins University School of Medicine inducted its first group of master educators. This is a student-led initiative aimed at creating a new model of teaching recognition based on student nominations, and it has been extremely well-received by faculty and students alike. This year’s inductees were announced at the beginning of March.

Peer-to-Peer Training and Resources

Another essential component of preclinical education involves peer-to-peer teaching. A common thread within the restructuring of medical education is that it is frequently student-driven. In fact, some of students’ favorite educational tools have been created by other students. When medical student Sam Roman went through the Genes to Society (GTS) curriculum, she meticulously typed notes from every single lecture and slide deck, paring down the curriculum to a no-nonsense, bullet-pointed summary of the most essential facts. She chose to share this resource with her fellow classmates, and now her famous “Roman Notes” have been used by hundreds of students.

“I really never thought [my personal notes] would reach an almost-legendary popularity with the classes to follow,” Roman now recalls. “I really think students appreciate the format for the same reasons I made them for myself — we have lots of competing interests and short attention spans, and the notes contain the important information with helpful graphics in an aesthetically pleasing way.”

quote: as we move forward as students, teachers, clinicians and scientists, we should remember to not only listen to our patients, but to listen to our learners as well. Sometimes students are the best teachers of all. -Benjamin OstranderAnother student, Divine-Favour Anene, started to compile slides and give review lectures to first-year students prior to each exam during his second year of medical school at Johns Hopkins. When asked about his motivation to create these lectures, Divine says he has “always loved teaching and seeing other people succeed,” and wanted to “provide a different ‘student perspective’ on content in the preclinical years.” As a current student, he has an intimate understanding of what topics are important, how they can be easily conveyed in the most fundamental and simple way, and what knowledge will be tested not only during GTS, but also on standardized exams, like the United States Medical Licensing Examination. This firsthand knowledge is something unique that a subspecialized clinical expert 30 years out of medical school often does not possess.

One of my favorite parts about the Johns Hopkins community is the way in which driven colleagues collaborate, teach, learn and push each other to be the best they can be. As we move forward as students, teachers, clinicians and scientists, we should remember to not only listen to our patients, but to listen to our learners as well. Sometimes students are the best teachers of all.


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Benjamin Ostrander

Benjamin Ostrander is a third-year medical student who strives to keep life infinitely interesting through creativity with words, food, music, medicine and more.

“I am Muslim,” says Nimrah Baig, a third-year medical student. Her words do not sound like a label, but rather a bold summation of an entire world that she slowly begins to introduce me to. “My faith is something I live every day. My actions, how I treat others and my goals in life are all manifestations of my faith.”

Quote: “My faith is something I live every day. My actions, how I treat others and my goals in life are all manifestations of my faith.” Nimrah BaigBaig prays five times a day, whether she is at home or in a busy hospital ward. She carries a foldable prayer rug in the pocket of her white coat and diligently plans around her clinical schedule so that she might be able to step aside briefly in between seeing patients. She thinks of it as a spiritual break. For Baig, praying is a necessity, as important as eating. She finds that praying gives her spiritual rejuvenation and creates an opportunity for team members to ask questions about her faith.

Prayer is merely one of five pillars of Islam. The other pillars include a declaration of Muslim faith, charity, fasting during Ramadan and pilgrimage to Mecca. A common theme in my conversations with other Muslim medical students was how the pursuit of a career in medicine allows them to actively practice sacrifice, generosity and caring for the underserved, all of which are major themes in Islam. “He who saves a life has saved the entirety of humanity” is one of the principles that Omar Najjar, a first-year medical student, strongly believes in. Rather than merely a religion, Najjar sees his relationship with his Islamic faith as all-encompassing. He self-identifies as a Muslim in the form of the culture and lifestyle that it represents.

Awa Sanneh, a third-year medical student, expresses her faith outwardly by wearing a hijab, or headscarf. She began wearing the hijab after undergoing a spiritual transformation during her high school years and has been on a “journey of self-refinement” ever since. There is a heavy sense of responsibility for Sanneh in wearing the hijab.

Did You Know? The five pillars of Islam include: - Salat: praying five time each day - Shahada: reciting the Muslim declaration of faith - Zakāt: making financial contributions to the poor - Sawm: fasting during Ramadan - Hajj: making a pilgrimage to Mecca. “By wearing the hijab, people see me as a representative of Islam,” she shares. Sanneh is also fully aware of the pressures of the current sociopolitical context in America, which have compelled local advocates, such as Adnan Hyder, a Bloomberg School of Public Health professor, to found the American Muslim Wellness Initiative at Johns Hopkins. She is thus even more intimately aware of the importance of being involved with the Muslim-American community, whether it is through attending faith-based events or pursuing her interest in Muslim-American health.

Through her scholarly research project, Sanneh discovered that Muslim communities in the United States are experiencing health care disparities, likely due to discrimination and a delay in seeking care. For Sanneh, her faith has thus become an essential part of how she sees herself serving her future patients and health care in America. She hopes that in the future, she can address these disparities and be an advocate for patients of her faith and heritage.


About this series:

Although medicine is often seen as a field that is distinct from religion, religious beliefs have a significant impact on the way physicians and medical students approach their training, interactions with patients, and understandings of disease and death. My fellow Biomedical Odyssey blogger Rabia Karani and I have created a short blog series on faith and medicine to give you a glimpse into the worlds of Johns Hopkins students who have been influenced strongly by and/or are actively practicing their faiths. 

We hope that you come away with a deeper understanding of the profound impact and immense strength that arises when peoples of faith seek to do good work in the medical field with all their hearts, minds and souls.


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Stephanie Zuo

Stephanie Zuo is a fourth-year medical student who believes in the healing power of a listening ear.

9th Annual Medical Student Research Symposium

Artwork by Halley Darrach, 2nd Year Medical Student

On Feb. 10, the Johns Hopkins University School of Medicine held its ninth annual Medical Student Research Symposium. The symposium, which coincides with the culmination of the Scholarly Concentration program that takes place during the first and second years of medical school, is an opportunity for Johns Hopkins medical students to showcase and exchange ideas about their research with their friends, faculty members and mentors. Aside from the traditional poster presentations, students are selected to present their research in oral presentations.

Sharing Research Outside the Lab

Traditionally, students have submitted research under a variety of categories, including but not limited to basic science, clinical science and the history of medicine. For some individuals, this experience was formative and influential throughout their years in medical school. Alexander Fischer, one fourth-year medical student who helped organize the event, observed: “Working on research at Hopkins has been one of the most rewarding aspects of my medical experience, so this is my way of giving back. I think the symposium is a great platform for students to showcase the research that they are doing in a setting that is structured similarly to a national conference but on a smaller scale and in a supportive and somewhat less formal setting.”

quote: I think the symposium is a great platform for students to showcase the research that they are doing in a setting that is structured similarly to a national conference but on a smaller scale and in a supportive and somewhat less formal setting.Fischer also noted that that the symposium has the potential to influence all students, not just those who choose to submit their work. “It gives medical students a chance to get a sense of the breadth of research that is being conducted by their peers here at Hopkins. It gives the first-year medical students a chance to become inspired about the research that they will be conducting during their time during the scholarly concentration.”

And the Winners are...

This year, the podium presentations ranged from clinical research focusing on antibiotic efficacy to the emergence of multidisciplinary pain clinics across the United States. Ultimately, three students walked home with prizes, being commended for both exceptional research and presentation skills: Anna Goddu, for her talk titled “Words Matter: Using Stigmatizing Language in Patient Charts Negatively Impacts Physician Attitudes and Dosing of Pain Medication”; Andrea Yonge, who presented “Circumstances, Locations, and Outcomes of Falls in Patients with Glaucoma”; and Victoria Huang, who discussed her work “New Regulatory T Cell Targets in Prostate Cancer.”

quote: It gives medical students a chance to get a sense of the breadth of research that is being conducted by their peers here at Hopkins.Aside from the large-scale podium presentations, several of the small-scale presenters were also recognized for their excellence in research, including Carson Woodbury, for his talk titled “Sexual Well-Being After Breast Cancer Surgery and Breast Reconstruction: A Systematic Review with Meta-Analysis,” and Jia Ahmad, for her presentation titled “The Emergence of an Epidemic: NIDA, Heroin, and the Birth of “Drug Abuse Epidemiology.” These projects, among the other speakers and nearly 100 posters on display, highlight the variety of research types, topics and the diverse interests of the students and faculty at Johns Hopkins.

Thanks to the Mentors

While these budding researchers displayed hard work and initiative, credit also needs to be given to the many mentors who helped with research and organized the symposium, including Dr. Mary Catherine Beach, Ms. Carly Wasserman and numerous scholarly concentration advisors. Without the supportive faculty members and mentorship at Johns Hopkins, such remarkable breadth and quality in student research would be much more difficult to achieve.


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Ruchi Doshi

Ruchi Doshi is a third-year medical student pursuing her M.P.H. She is also an avid cook and baker who loves everything Bollywood.

For many obese people, losing and maintaining weight is a constant struggle. It often takes several months of careful dieting and exercise to see results, but those stubborn pounds frequently come back within weeks. One of the common causes of this cyclical pattern of weight gain is that the body can respond to calorie restriction by drastically reducing its metabolic rate. Bariatric surgery is often promoted as an option for such people.

What is Bariatric Surgery?

Bariatric surgery includes reducing the size of the stomach, either with a gastric band, which reshapes the stomach to create a small pouch and bypassing a portion of the stomach (gastric bypass), or by removing a small portion of the stomach altogether (sleeve gastrectomy). Both procedures can cause corresponding changes in the small intestine as well. These procedures spur weight loss by restricting the amount of food the stomach can hold, increasing feelings of fullness and reducing the absorption of nutrients. It has been observed that bariatric surgery has beneficial effects not only for treating obesity, but for type 2 diabetes as well.

Gastric bypass surgery includes re-routing your stomach in order to feel full and eat less.

Gastric bypass surgery includes re-routing your stomach in order to feel full and eat less.

Can Bariatric Surgery Benefit Patients with Diabetes?

A recent study lead by Philip Scheuer of Cleveland Clinic looked at long-term (five-year) outcomes of a clinical trial that compared bariatric surgery versus medical therapy. The patients were randomly divided into three groups — a bariatric surgery group treated with gastric bypass and provided with diet support, a bariatric surgery group treated with sleeve gastrectomy and provided with diet support, and a medical therapy group that involved keeping track of medication and education about diet and exercise related to diabetes. The study, named STAMPEDE (Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently), was published in the Feb. 16 issue of The New England Journal of Medicine and indicated that compared to those with diabetes who followed medical therapy, patients who underwent gastric bypass showed more significant improvements in glycemic control.

The study included 150 patients with an average age of 49 years, average body mass index of 37 and an average glycated hemoglobin level (HbA1c) of 9.2 percent. HbA1c is a clinical measurement used to assess blood sugar levels and is considered the gold standard for monitoring glycemic control in patients with diabetes. Patients with an HbA1c below 6 percent are considered healthy, whereas a result between 6 and 6.4 percent is an indicator of prediabetes, and anything above 6.5 percent is diabetes.  The patients were randomly assigned into two groups — one underwent either gastric bypass or sleeve gastrectomy, and the other received medical therapy alone. The goals were to monitor their HbA1c levels and to lower HbA1c levels to 6 percent or below, which is indicative of well-controlled diabetes.

Study Findings

After five years of follow-up, 5 percent of the medical therapy-only group had achieved an HbA1c level of 6 percent or less, whereas 29 percent of the surgical intervention group had reached this goal. Patients who underwent surgery also showed other improvements, such as losing significantly more weight, more significant reductions in waist circumference, dramatically lower triglycerides and cholesterol levels, and better quality of life than those who were treated with medication alone.

Although the observation that patients with type 2 diabetes have better glycemic control after bariatric surgery is not new, most studies until now were observational and included only severely obese patients. The current study is the first randomized controlled study of this scale. Another important conclusion from this study involved patients with body mass index between 27 and 34. Most insurance companies will cover bariatric surgery for people with a body mass index of 40 or higher, or alternatively, 35 or higher (in the presence of other comorbidities). However, this study shows that even patients with a body mass index of 27 to 34, significantly below these cutoffs, benefited from the procedure as compared to those with medical intervention alone.

Lastly, the study found that gastric bypass led to greater weight loss with fewer diabetic medications and thus appears to have an advantage over sleeve gastrectomy. However, the authors caution that their trial was not designed to detect other small but clinically significant differences between the two procedures. There might be additional advantages of gastric bypass over sleeve gastrectomy that might be uncovered by trials designed to address those questions specifically.

References
Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 5-Year Outcomes
Bariatric surgery procedures
A Guide to HbA1c


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Monika Deshpande

Monika Deshpande is passionate about science communication. When she was a postdoc at the National Institutes of Health, she was involved in several publications, such as The NIH Catalyst and NIH Research Matters. She is adept at interviewing scientists and showcasing their achievements, and is able to write for scientific and nonscientific audience.

How does spaceflight change the human body? Scientists have known for many years that traveling to space leads to cellular changes. Spaceflight can weaken bones, suppress the immune system, damage DNA and potentially contribute to cancer.

A unique study of identical twins seeks to expand our knowledge of the impact of space travel on the human body. As part of the NASA Human Research Project Twins Study, astronaut Scott Kelly returned home in March 2016 after spending nearly a year living aboard the International Space Station. Throughout that year, he was able to collect blood samples and send them back to Earth. Meanwhile, his identical twin, Mark, also gave blood samples, serving as an experimental, Earth-bound control. Scientists could then run the same tests on Scott’s and Mark’s samples and compare the results. A difference between the twins’ results — or alternatively, a change in Scott’s results during spaceflight that returned to baseline measurements when he returned to Earth — could point to previously unrecognized effects of spaceflight on the human body.

The preliminary results of 10 different projects ranging from fields as broad as immunology to cognitive sciences were recently presented at NASA’s Investigators’ Workshop, held Jan. 23 to 27 in Galveston, Texas. Scientists reported that spaceflight altered the levels of inflammatory markers, increased the length of telomeres (repetitive DNA sequences that protect the ends of chromosomes) and shifted the populations of commensal bacteria that make up the gut microbiome, among other findings.

Lindsay Rizzardi and Andy Feinberg practice pipetting at zero gravity on the "Vomit Comet."

Lindsay Rizzardi and Andy Feinberg practice pipetting at zero gravity on the "Vomit Comet."

One project of particular interest to the Johns Hopkins community is that of investigator Andy Feinberg and postdoctoral fellow Lindsay Rizzardi. They are investigating whether spaceflight leads to epigenomic changes, or changes to how DNA and DNA-associated proteins are modified in a cell. Whereas the DNA sequences of identical twins like Scott and Mark Kelly are the same, modifications to the DNA or its packaging proteins may differ due to environmental factors and reflect changes in gene activity.

Rizzardi and Feinberg found that the genomewide level of DNA methylation — the addition of a methyl group at specific sequences — decreased in Scott while he was in space and returned to his baseline measurements after returning to Earth. Scott’s methylation patterns also showed more epigenetic “noise,” or variability, in space. According to Rizzardi, these results may suggest that “the epigenome can respond to conditions in space to allow more flexibility in gene expression to cope with this extreme environment.” She is now integrating her data with other investigators’ data sets — including measurements of gene expression, metabolomics and telomere length — to understand the effects of changes in DNA methylation on a systems biology scale. Rizzardi was drawn to this project because “it is the first time human genomics research has been conducted in space” and hopes that this research will “open the door to genomics research being conducted by NASA on a broader scale in the future.”

Rizzardi, Feinberg and others have also pioneered ways to perform basic laboratory techniques, including DNA sequencing, in space. In August 2016, astronaut Kate Rubins successfully sequenced DNA samples on the International Space Station that were prepared on Earth. Future astronauts may be able to prepare and test their own samples at microgravity. They can then use these techniques to collect further data on the effect of spaceflight on the human body or better understand and be able to diagnose illness on long space missions. Ultimately, a hope is that this technology could even be used to identify extraterrestrial life forms that have DNA.


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Alisa Mo

Alisa Mo is an M.D./Ph.D. student who's passionate about the intersection of neuroscience, genomic medicine and society. She’s also a pianist and enjoys cooking.

hand holding out nutritional supplementsWhat do an anti-parasitic drug used to treat pinworms and a frequently used anti-malarial drug have in common? According to recent studies from the labs of Johns Hopkins and University of Kentucky investigators, both mebendazole and chloroquine could be promising medicines to combat cancer.

Mebendazole has been in use as an anti-helminthic drug since 1971. Within the last few years, mebendazole has been added to the growing list of medications that are part of a movement to repurpose already FDA-approved drugs for novel or unexpected purposes. This renewed interested in already approved pharmaceuticals has stemmed from the immense amount of time, money and research that must be put in after identifying a novel compound before the drug can move on to clinical trials, with the time from target identification to FDA approval averaging 14 years.

FDA approval takes about 14 yearsBy testing compounds that have already passed the rigorous testing requirements for human consumption, researchers are able to circumvent a lot of the costly and time-consuming parts of drug development, speeding up the time to clinical trials significantly. Mebendazole has already been the focus of several preclinical and clinical trials, including as a treatment for lung cancer, but it has been also found to be potentially beneficial for other cancers, including glioblastoma, the most common and aggressive form of primary brain cancer.

In a serendipitous turn of events, Gregory Riggins of Johns Hopkins and his team at the Brain Cancer Biology and Therapy Research Laboratory discovered that pinworm-infected mice, which were treated with mebendazole, did not develop appreciable brain tumors, even though the researchers had implanted brain cancer cells weeks before. In subsequent experiments, his team demonstrated that administration of mebendazole prevented tumor proliferation and improved survival times in mice by an average of 63 percent. Currently, mebendazole is part of a phase I clinical trial for patients with newly diagnosed, high-grade glioma and glioblastoma.

Similarly, the anti-malarial compound chloroquine showed surprising properties in combating cancer and tumor growth in a series of experiments led by a group at the University of Kentucky. In a metastatic cancer mouse model, chloroquine led to the production of a specific tumor suppressor protein called Par-4. Par-4 plays a key role in inhibiting tumor cell proliferation, especially in tumor cells that lack p53, which is a well-studied, important tumor suppressor that is commonly inactive in cancerous cells, allowing growth to occur uncontrolled. Tumor cells missing p53 are often refractory to treatment, but compounds that increase production of other tumor suppressors can often compensate for p53 deficiencies and control cancerous growth, leading to hope that chloroquine as a repurposed drug could be promising for treating such cancers.

Both highlighted drugs still need to pass a rigorous battery of studies and clinical trials, and more in-depth research regarding the mechanism by which each combats cancer needs to be done. However, with pre-existing FDA-approved drugs potentially serving double duty as powerful oncologic therapies, cancer patients may soon have more options at hand for improved health and quality of life.

References:
Repurposing an Antiparasite Drug to Fight Glioblastoma
A Pinworm Medication Is Being Tested As A Potential Anti-Cancer Drug
Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis
New Study Shows Promise for Repurposing Anti-Malarial Drug for Cancer Treatment
Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme
Tackling the Bottlenecks in the Drug Development Pipeline


 

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Adela Wu

Adela Wu is passionate about making connections between ideas and people, and seeing how her interests in literature, creative writing and medicine play out in that theme. In addition, she also enjoys river and sea kayaking, having recently whitewater kayaked the Shenandoah River rapids.

No one prepares you for listening to a lecture about how your mother died. Medical students are trained to recognize grief and distress in patients and invite them to talk about it. We are taught the complex molecular physiology behind diseases common and rare, minor and terminal. But we are not trained to see our own family’s tragedy writ large on a lecture screen, broken down into bullet points and illustrated with surgical images.

For me, this moment came on a chilly January morning in the third week of our reproductive systems course. The schedule listed two lectures on ovarian disorders: the first on benign diseases, like cysts and infections, and the second on cancer.

At the end of the first hour, the professor introduced a case example. The patient was a woman in her early 30s with three months of mild abdominal pain. As we worked through the history, lab values and imaging, it became clear: This was no infection or benign cyst. This young woman had ovarian cancer. The lecturer went on to describe the chosen treatment plan, but I barely heard. My mind had been yanked 22 years away, paralyzed with the sudden reminder of another young woman’s cruel diagnosis: my mother’s. A board-certified anesthesiologist, marathon runner and mother to two boys, she died from an aggressive ovarian cancer on May 1, 1995. She was 34.

Carson Woodbury with his mother

Carson with his mother. Image courtesy Kate Kuhn Woodbury

I heard the class applaud. My friend Eva, who knew about my mom, leaned over and asked me how I was doing. Looking at my computer, I thanked her for asking and mumbled something about the last case being a doozy. I had a minute or two before the second lecture began. I’m still doing okay, I thought. I can still do this. I desperately wanted to understand this disease. But the more I thought about it, the sadder I became. I can’t do this, not now.

Not wanting to make a scene, I grabbed only my laptop and left the hall, focusing on walking at a normal pace. Then, I found a study room with no windows, slumped against the wall and let down my guard.

It was seven days before I finally willed myself to watch the recording of the lecture. It fit the familiar pattern of a cancer talk — risk factors, clinical features, pathology, etc. — but this time sprinkled with pieces of information that jabbed into my stomach like ice picks.

May not feel mass on pelvic exam until >8 cm.

My dad once said my mom’s tumor looked like the Death Star on her CT scan.

An intraoperative photograph showing an abdominal cavity littered with yellowish lobes of metastatic cancer.

quote: I couldn’t shake the stunning awe that every cancer, every disease I learned about in medical school provokes this visceral reaction from someone, somewhere because it has touched their life like ovarian cancer irrevocably altered mine. Picturing my mother’s youthful cream-white skin cut with a scalpel and lifted up by cold steel retractors to reveal disease scattered far from its ovarian origin.

No overall survival advantage for CA-125 screening in average- risk women.

We still don’t have a way to catch it early.

All the while, I couldn’t shake the stunning awe that every cancer, every disease I learned about in medical school, provokes this visceral reaction from someone, somewhere because it has touched their life, like ovarian cancer irrevocably altered mine. How many of my classmates, I wondered, who didn’t attend a particular lecture had excused themselves because they were too sad, because the featured disease had once scarred their family? How will we fare caring for our first patients suffering from diseases we could name before we could spell “surgeon”?

Illness touches all of us. New medical students are not blank slates. We arrive carrying the weight of our family’s collective experience with health and the medical system. I am far from understanding the full impact of my mother’s death on my life in medicine, but I am one step closer to understanding her disease and how I can care for patients whose diagnosis cuts me to my core.

quote: I am far from understanding the full impact of my mother’s death on my life in medicine, but I am one step closer to understanding her disease and how I can care for patients whose diagnosis cuts me to my core.Ovarian cancer has a face and a name and a story for me. Ovarian cancer will forever be represented by my mother. But there are countless more diseases for which I don’t have a story. In a few weeks, my classmates and I will enter the hospital to begin learning the human stories with which to illustrate our textbooks. Faces will replace PowerPoint slides. Conversations will supplant bulleted lists. A slice from a CT scan will lose its abstractness and become a window into understanding Ms. F’s bloody cough. Disease will gain a face and a name and a favorite takeout dinner. Disease will become human. And then we’ll go to work.


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Carson Woodbury

Carson Woodbury relishes a good detective story. Drawing early inspiration from Scooby-Doo’s Mystery gang, he fell in love with the natural world and all its enigmas — from Herodotus to developmental genetics. He is a second-year medical student, an aspiring mountaineer and an avid reader of The Baltimore Sun. His dream job is chief medical officer of a starship.