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listening to
the heart’s
smallest
messenger
How this device
gets cells to tell




research
A PublicAtion of The ReseaRch InsTITuTe aT naTIonwIde chIldRen’s hospITal
research is dedicated to the
mission of informing and inspiring
readers by highlighting scientific
                                             table of contents                                                                        a message from the president
performance at the Research
institute at nationwide children’s
Hospital. this publication is
produced biannually by the
Marketing and Public Relations
Department at nationwide
children’s Hospital.
                                                                                                                                      Dear Friends and Colleagues:

                                                                                                                                      One of the prevailing joys of being a scientist is the knowledge that each day could
                                             fe at ure s
                                                                                                                                      be a day of fascination and revelation. The intellectual pursuit of a life-altering
                                             4    wanted: a Generation of Quitters                                                    discovery, particularly one that could improve the life of a child, drives us to
                                                  brady Reynolds, PhD, has never smoked a cigarette in his life.
                                                                                                                                      continue our years of research.
                                                  Yet most of his day is spent trying to find ways to quit.
                                                                                                                                      Our excitement and fascination shouldn’t stay within our walls. We want to share
le a deRs hIp                                8    The Importance of studying adolescents                                              these experiences with you. So welcome to our first issue of reSearch.
The Research Institute at                         What if in addition to the normal awkwardness of adolescence,
nationwide children’s hospital
                                                  you are diagnosed with an illness that will last a lifetime? findings               Within these pages, you will discover how impulsive thought processes affect a teen’s
John a. Barnard, Md
                                                  suggest that adolescents shouldn’t be treated like adults, but they
President                                                                                                                             ability to quit smoking; be privy to the way heart cells “communicate” and what they
                                                  shouldn’t be treated like children either.
lauren o. Bakaletz, phd                                                                                                               say about heart disease; and be revealed to the world of an adolescent facing a chronic
Vice President, Basic Sciences Research
Kelly Kelleher, Md, Mph
                                             12   listening to the heart                                                              GI illness, and how we are searching for the ideal ways to treat this condition.
Vice President, Health Services Research          Down at the cellular level lives the cardiac myocyte, the heart’s
                                                  smallest messenger. Although it is simply a microscopic cell extracted              Join us in our enthusiasm for the future of pediatric research and in the milestones
Grant Morrow III, Md
Medical Director                                  from the heart muscle, it has a story to tell. that is, if you’re listening.        – sometimes incremental and sometimes monumental – we reach each day in our
daniel R. Mann                                                                                                                        pursuit of discovery.
Vice President, Research Administration
and Operations
                                             e xt ras
Katherine s. Milem
Vice President, Research Business Services   7    noteworthy
                                                  news about the Research institute and its faculty.
research
Writer and editor                            16   Into the Future                                                                     John Barnard, Md
Melissa hamilton                                                                                                                      President
                                                  the look of Research in 2012.
                                                                                                                                      the Research institute at nationwide children’s Hospital
Designer
Tanya Bender
                                                                                                                                      Professor of Pediatrics
Photographers
                                                  o n tHe co v eR                                                                     the ohio State university college of Medicine
Brad smith
dan smith                                         Loren E. Wold, PhD, examines a device used to study the function of heart
                                                  muscle cells, a tool that could change the way science understands heart disease.
Manager, Research communications
Jan arthur

contact us at
ResearchMagazine@nationwidechildrens.org




                                                                                                                                                                                                                            research | 3
to complete the eDt, the participant
                                                                                                                                        views a computer screen that displays
                                                                                                                                        two monetary amounts, one that
                                                                                                                                        offers a smaller immediate reward and
                                                                                                                                        another that offers the possibility of a
                                                                                                                                        larger reward at a delayed time. for
                                                                                                                                        example, do you want 15 cents now or
                                                                                                                                        the possibility of 30 cents 28 seconds
                                                                                                                                        from now? if the participant clicks the




  Wanted:
                                                                                                                                        computer to choose 15 cents now,
                                                                                                                                        coins come clinking out of a specialized
                                                                                                                                        change machine that is connected to                                                               Brady Reynolds, PhD, demonstrates
                                                                                                                                        the computer.                                                                                       the Experiential Discounting Task.

                                                                                                                                        “that’s why it’s called the experiential

  a Generation of Quitters                                                                                                              Discounting task. Participants actually
                                                                                                                                        experience the choice they make at
                                                                                                                                        that moment,” said Dr. Reynolds.
                                                                                                                                                                                   the program at nationwide children’s
                                                                                                                                                                                   in January of 2006, one of the first-
                                                                                                                                                                                   and-only smoking cessation programs
                                                                                                                                                                                                                               these findings have implications for
                                                                                                                                                                                                                               designing effective smoking cessation
                                                                                                                                                                                                                               programs. “A person who discounts
  HoW ReSeARcH iS finDing neW WAYS to HelP ADoleScentS Quit SMoking
                                                                                                                                                                                   for adolescents in central ohio.            most by delay is someone whose




   B
                                                                                                                                        if the participant instead chooses 30                                                  behavior is led by more immediate
               rady Reynolds, phd, has        to smoke into adulthood, practically          a larger reward that is delayed for a       cents, they have to wait a set period of  Adolescents who enroll in this pro-
                                                                                                                                                                                                                               consequences. to reach an adoles-
               never smoked a cigarette       guaranteeing increased health risks,          period of time. Delay discounting has       time to see if they will actually receive gram attend a smoking cessation
                                                                                                                                                                                                                               cent smoker who discounts a great
               in his life. Yet most of his   since approximately half of people            been shown to play an important role        the money, since the delayed option       class held at nationwide children’s
                                                                                                                                                                                                                               deal, you need to make the benefits
               day is spent trying to find    who smoke are expected to die from            in cigarette smoking behavior.              may not actually pay out each time.       main campus once a week for 10
                                                                                                                                                                                                                               of quitting smoking more immediate.
               ways to quit.                  smoking-related illnesses, according                                                      this time delay can vary from zero        weeks. During the first half of the
                                                                                                                                                                                                                               Programs that stress the long-term
                                                                                            to further understand this relation-        seconds, 7 seconds, 14 seconds, to        program, participants are taught
                                              to the World Health organization.                                                                                                                                                effects of smoking are going to be less
   You won’t see him crunching on a                                                         ship, Dr. Reynolds has developed a          28 seconds. After the time delay, the     health and smoking education
                                                                                                                                                                                                                                                   effective for these
   piece of nicotine gum or slapping on       Although adolescent smokers often             delay discounting task that he believes     selected money                                                                                             adolescents,” said
   nicotine patches. instead, you’ll find     continue their habit into adulthood,          overcomes some of the shortcomings          amount appears             “That’s why it’s called the experiential                  discounting Dr. Reynolds.
   him crunching numbers and trying           it may not always be clearly by               of previously developed methods.            in the computer’s
   to patch holes in research about what      choice. Sixty-one percent of adoles-                                                      “bank account”               Task. participants actually experience                  the choice             Although Dr.
                                                                                            Most delay discounting tasks ask
   motivates adolescents to quit smoking.     cents report wanting to quit smoking
                                                                                            participants to choose between
                                                                                                                                        that will be cashed           they make at that moment,” said dr.                    Reynolds.              Reynolds is quick
                                              cigarettes and 59 percent report a                                                        out once the par-                                                                                           to suggest his
   that’s because as a principal investi-                                                   hypothetical situations, such as,
                                              quit attempt in the past year.                                                            ticipant has completed the entire task.   including the common myths of                 findings could be applied to current
   gator in the center for biobehavioral                                                    would you prefer $10 now or $100
                                                                                                                                                                                  smoking. class five is the required           smoking cessation programs, he says
   Health at the Research institute at        So why can’t they just quit? that’s           one year from now. but according to         every time the participant chooses        “smoking quit date” for participants          that even the best of research needs to
   nationwide children’s Hospital Dr.         what Dr. Reynolds wants to find out.          Dr. Reynolds, this hypothetical method      the smaller, immediate amount, that       and the remaining sessions are used           be strengthened by further evidence.
   Reynolds is using research techniques                                                    can be tricky for adolescents.              quantity goes down for the next choice
                                              As a behavioral psychologist, Dr.                                                                                                   as a support group to help deal with          that’s why he has made the eDt
   to learn how to help adolescents                                                                                                     (the next option may give you 10
                                              Reynolds has spent his career trying          “because adolescents, particularly                                                    withdrawal and lifestyle changes              available via the web for behavioral
   become quitters.                                                                                                                     cents). this calculation helps provide a
                                              to understand what motivates people           younger adolescents, aren’t as psycho-                                                associated with quitting smoking.             laboratories throughout the world.
                                                                                                                                        clearer measure of delay discounting.                                                   other investigators can access the
   “Adolescence is a sensitive period to      to certain behaviors. Although some           logically developed in many ways as
                                                                                                                                        those who chose the smaller, immedi-      Participants of the n-o-t program at
   begin smoking,” said Dr. Reynolds.         motivators tied to cigarette smoking          adults; they perceive information differ-                                                                                           software, purchase the appropriate
                                                                                                                                        ate reward more often than the larger,    nationwide children’s Hospital can
                                              have already been identified, such as         ently,” said Dr. Reynolds. “for example,                                                                                            coin machine and conduct their own
   According to surveillance by the                                                                                                     delayed option are described as being     choose whether or not they want to
                                              impulsivity, there is still a lot to learn.   they don’t seem to understand the con-                                                                                              experiential delay discounting studies.
   Morbidity and Mortality Weekly Report,                                                                                               more impulsive discounters.               perform the delay discounting task
                                                                                            cept of time (like a year) as adults do.”                                                                                           Dr. Reynolds will then analyze their
   approximately 2,000 adolescents            “impulsivity is not described by one                                                                                                along with their participation in the
                                                                                                                                        to determine how delay discounting                                                      findings from the eDt, in hopes that
   initiate smoking each day. that means      type of behavior. it is multifaceted,”        that’s why Dr. Reynolds developed                                                     10-week program. Dr. Reynolds’ delay
                                                                                                                                        relates to cigarette smoking behavior,                                                  they can also help shape smoking
   that every minute, an adolescent is        said Dr. Reynolds.                            the experiential Discounting task                                                     discounting studies with this adolescent
                                                                                                                                        the eDt is being evaluated with an                                                      cessation and education programs
   trying a cigarette for the first time.                                                   (eDt), a computer-based program                                                       smoking population have shown that
                                              A recently studied aspect of impulsivity                                                  adolescent smoking cessation program                                                    for adolescents.
                                                                                            that measures delay discounting by                                                    the adolescents who discount more
   And that first time may not be the         is delay discounting. Delay discount-                                                     called not-on-tobacco (n-o-t), the        often are those who are less likely to        More Smoke Signals
                                                                                            requiring participants to choose
   last. Studies show that the majority of    ing describes an individual’s preference                                                  official teen smoking cessation           quit smoking, even after participating        the eDt is not the only method
                                                                                            between moment-in-time situations as
   adolescents who smoke daily continue       for a smaller, immediate reward over                                                      program of the American lung              in the n-o-t program.                         Dr. Reynolds is using to understand
                                                                                            opposed to hypothetical situations.
                                                                                                                                        Association. Dr. Reynolds initiated
4 | research                                                                                                                                                                                                                                                   research | 5
Circulatory System Could Provide New Strategy for Mus-
                                                                                                                                                      cular Dystrophy Gene Therapy Future Study to Monitor
                                                                                                                                                      Medication Usage and Effects Technique Helps Diagnose
                                                                                                                                                      Asthma Attacks Circulatory System Could Provide New
                                                                                                                                                      Strategy for Muscular Dystrophy Gene Therapy Future
                                                                                                                                                      Study to Monitor Medication Usage and Effects Tech-
                                                                                                                                                      nique noteworthy |
                                                                                                                                                             Helps Diagnose Asthma Attacks Circulatory Sys-
                                                                                                                                                                                                     tHe ReSeARcH inStitute At nAtionWiDe cHilDRen’S HoSPitAl



                                                                                                                                                                          Circulatory System Could Provide               the system alerts a trained psychiatric nurse to contact the
                                                                                                                                                                          New Strategy for Muscular Dystrophy            patient or parent and when necessary, contact the patient’s
                                                                                                                                                                          Gene Therapy                                   physician or hospital emergency services.
   preliminary results have shown that the participants                                       Although Dr. Reynolds would like to                                         investigators at the Research institute have
                                                                                              delve into these new areas of research,                                                                                    the PhaSt project could provide medication monitoring in
   significantly maintained abstinence from smoking                                                                                                                       received an $8.1 million grant from the
                                                                                              he is not abandoning the eDt. in fact,                                                                                     instances when families or the overstretched child mental
                                                                                                                                                                          national institutes of Health to learn more
   when they were being paid, even during a period at                                         fellow principal investigators at the                      about strategies to treat muscular dystrophy, potentially
                                                                                                                                                                                                                         health systems do not have the resources to follow the
                                                                                              Research institute have plans to use it                                                                                    recommended–often weekly–physician visits.
   the end of the program when it didn’t matter how                                                                                                      leading to two new gene therapy approaches. the primary
                                                                                              to determine the role delay discounting                    research strategy will use the circulatory system for gene
   much they smoked.                                                                          plays in behaviors beyond smoking                          delivery of the dystrophin gene, as opposed to direct
                                                                                                                                                                                                                         the study is expected to begin in early 2008 and continue
                                                                                                                                                                                                                         through 2010. initial funding for the study was made
                                                                                              cessation. Planned studies include                         injections into individual muscles. this vascular delivery
   smoking behavior. Working with              program style would encourage                                                                                                                                             possible by a collaborative grant between nationwide
                                                                                              measuring suicidal impulsivity and                         strategy provides a more favorable opportunity for
   collaborators, he is collecting data from   maintenance by providing the needed                                                                                                                                       children’s and the ohio State university.
                                                                                              studying what makes people likely to                       correction of lost function throughout the body reaching
   a web-based contingency management          peer support group,” said Dr. Reynolds.        use safety equipment, such as sports                       many muscles, as well as the heart.                                              Study Helps Differentiate Between
   program. Participants of this program                                                      safety equipment or parent use of infant
                                               until then, the n-o-t program                                                                                                                                                              Asthma and Vocal Chord Dysfunction
   are asked to record “video diaries” of                                                     car seats and home smoke alarms.                                            Two Centers of Emphasis Obtain
                                               continues to make an impact. of the                                                                                                                                                        Doctors at nationwide children’s Hospital
   themselves three times a day using web                                                                                                                                 Leadership
                                               more than 60 adolescents who have                                                                                                                                                          performed a clinical study using spirometry
   cameras. At the time of each “diary                                                        even though Dr. Reynolds’ original                                          Bill smoyer, Md, Robert c. kelsch chair
                                               participated in the n-o-t program at                                                                                                                                                       in the emergency Department to identify
   entry” they blow into a picometer, a                                                       plans for the eDt were focused on                                           of Pediatric nephrology at the university
                                               nationwide children’s, 25 percent                                                                                                                                                          adolescents who had findings suggestive
   device used to measure carbon                                                              adolescents, his findings may have                                          of Michigan, has been appointed director
                                               made a significant decrease in smoking                                                                                                                                    of vocal chord dysfunction (vcD) compared to an acute
   monoxide levels, a distinct marker                                                         implications for adult smokers. “the                                        of the center for clinical and translational
                                               frequency and many of the others                                                                                                                                          asthma attack. the manuscript was published in the July
   of how much tobacco someone has                                                            research would have to be explored, but                    Research at the Research institute. Dr. Smoyer will work
                                               report at least some decrease.                                                                                                                                            issue of Pediatric Pulmonology.
   smoked in the past three to six hours.                                                     there are indications that these findings                  to orchestrate further development of clinical and
   Participants are given money for            Genetic Contributions                          may apply to the adult population since                    translational research across the organization.                 According to the study, 12 of the 17 adolescents who
   continued abstinence during the             beyond his current research methods,           research has already shown that adult                                                                                      presented to the emergency Department with difficulty
   treatment phases.                           Dr. Reynolds would like to further the         smokers discount more than adult                                           After serving in an interim position,           breathing, but with high normal oxygen levels, were
                                               understanding of adolescent smoking            non-smokers,” he said.                                                     leif nelin, Md, has been appointed              found to have evidence of vcD on spirometry. this led
   Preliminary results have shown that the                                                                                                                               director of the center for Perinatal
                                               cessation by investigating how genetics                                                                                                                                   to a change in the therapy for these patients. Spirometry
   participants significantly maintained                                                      for now, however, Dr. Reynolds plans                                       Research at the Research institute.
                                               contribute to smoking habits. He and                                                                                                                                      used in the acute setting of difficulty breathing can help
   abstinence from smoking when they                                                          to focus his research on ways to help                                      Dr. nelin plans to continue to improve
                                               chris bartlett, PhD, principal investiga-                                                                                                                                 differentiate vcD from asthma attacks.
   were being paid, even during a period                                                      adolescents specifically. “if we can                                       the integration between the center for
                                               tor in the center for Quantitative and         change smoking habits during
   at the end of the program when it                                                                                                                     Perinatal Research and the Division of neonatology,             the study suggests that if more emergency departments
                                               computational biology at the Research          adolescence, we’ll be able to greatly
   didn’t matter how much they smoked.                                                                                                                   an ability he demonstrated during his interim position.         made use of the spirometry test, it could cut down on the
                                               institute, are already collecting pilot data   reduce the long-term effects of                                                                                            number of children who are misdiagnosed and potentially
   With continued funding, Dr. Reynolds        that involves isolating genes associated       smoking,” said Dr. Reynolds.                                               Future Study to Monitor Medication              hospitalized.
   hopes to maintain this method of            with different neural systems in the                                                                                      Usage and Effects
   research with the hopes of one day          brain (many of which are associated            For more information about the                                             A research study is planned to trial a
   combining the contingency manage-           with addiction) to search for genetic          not-on-Tobacco program at                                                  new technology that helps monitor how
   ment model with the n-o-t program           markers of delay discounting.                  nationwide children’s hospital,                                            medications, specifically anti-depressants,
   model, for a more comprehensive                                                            call (614) 355-3445, or click on                                           are used in children and teens.
                                               other hopeful genetic studies include          “education classes” at
   smoking cessation course.
                                               investigating recent research in the field     nationwidechildrens.org.                                   the project, named “PhaSt”, or Pharmaceutical Safety
   “by reinforcing positive behavior,          that suggests the relationship between                                                                    tracking: Managing Medications for Patient Safety, involves
                                                                                                                                                                                                                           Learn about more research
   the contingency management portion          smoking behavior in parents and their          Further Reading: Reynolds, b.; Patak, M.; Shroff,          an interactive voice response telephone system to contact         news and highlights at
   could help kids get through the             children can most likely be accounted          P. “Adolescent smokers rate delayed rewards as less
                                                                                                                                                         parents or teenage patients. the system requires simple yes
   withdrawal stage that is common             for by their genetic relatedness, not just
                                                                                              certain than adolescent nonsmokers.” Drug and Alcohol
                                                                                              Dependence, v. 90 issue 2-3, 2007, p. 301-3.               or no answers to questions about the medications and their        NationwideChildrens.org/research.
   with the early days of smoking              by a child mimicking parental behavior.                                                                   side effects. When a parent or patient indicates a problem,
   cessation. then combining the n-o-t


6 | research                                                                                                                                                                                                                                                              research | 7
“IBD is an ideal disease for investigating adolescent adjustment to
                                                                                                                                            chronic illness, given its adolescent onset, and embarrassing, socially
                                                                                                                                            limiting, and appearance-changing symptoms.”




                                                                                                                  children’s Hospital, are studying adolescents to better       research on adolescent adjustment to other conditions,
                                                                                                                  understand how this patient population adjusts to             either,” said Dr. Mackner.
                                                                                                                  chronic illness.
                                                                                                                                                                                overall, a comprehensive adolescent perspective is lacking.
                                                                                                                  Although their research might not be poetic, what their       “the research on psychosocial adjustment to pediatric
                                                                                                                  findings suggest seems to be worth writing home about:        chronic illness has focused primarily on children. if adoles-
                                                                                                                  adolescents shouldn’t be treated like adults, but they        cents are included in this research, they are often included
                                                                                                                  shouldn’t be treated like children either.                    in the same sample with younger children. even when
                                                                                                                                                                                adolescents are the focus, development issues are often
                                                                                                                  The Uniqueness of Adolescence                                 not taken into account,” said Dr. Mackner.
                                                                                                                  Adolescence involves more changes than any
                                                                                                                  developmental period other than infancy.                      When Drs. Mackner and crandall refer to adolescents, they
                                                                                                                                                                                mean those age 11 through 18, since this is the period
                                                                                                                  these years are wrought with extreme biological changes       when most changes in psychosocial adjustment appear.
                                                                                                                  including raging hormones, acne, and increased body           So, why should an 11-year-old be categorized separately
                                                                                                                  odor and body hair.                                           from an 8-year-old? When it comes to psychosocial
                                                                                                                  on top of the stressors normally associated with adoles-      development, adolescence and childhood are worlds
                                                                                                                  cence, imagine having an incurable condition in which         apart. Adolescents spend significantly more time with
                                                                                                                  your main symptoms include diarrhea, rectal bleeding,         their peers than children do. close friends begin to
                                                                                                                  abdominal pain and delayed puberty.                           surpass parents as a primary source of social support and
      Wallace Crandall, MD and Laura Mackner, PhD                                                                                                                               acceptance by peers plays an important part of adolescent
                                                                                                                  inflammatory bowel diseases (ibDs) such as crohn’s            self-identity. involvement in extracurricular activities
                                                                                                                  disease and ulcerative colitis are chronic conditions in      contributes not only to acceptance by peers, but also


                     The Importance of
                                                                                                                  which inflammation in the intestines can result in these      takes on an important role for those planning to apply
                                                                                                                  sometimes embarrassing symptoms. Although ibD has             to college. in addition, the development of romantic
                                                                                                                  typically been viewed in the medical community as an          relationships becomes a significant focus.


                    Studying Adolescents                                                                          adult disease, about 25 percent of ibD cases occur in the
                                                                                                                  pediatric population, with the majority beginning their
                                                                                                                  onset in adolescence. Adjusting to the normal changes
                                                                                                                  adolescence brings is tough enough; adolescents with
                                                                                                                                                                                When Illness Adds Insult to Injury
                                                                                                                                                                                With so many aspects of psychosocial development how
                                                                                                                                                                                do you study whether or not an adolescent is adjusting
                                                                                                                                                                                well to this new stage of life?
                                     Researchers work to understand chronic                                       ibD are given even more to adjust to.
                                       Illness in a neglected Field of study                                      “ibD is an ideal disease for investigating adolescent         “there are two main aspects of studying psychosocial
                                                                                                                  adjustment to chronic illness, given its adolescent onset,    functioning,” said Dr. Mackner. “one is psychological



                    A
                                                                                                                  and embarrassing, socially limiting, and appearance-          functioning: Are they depressed? Do they have anxiety?
                             poet once remarked, “You don’t have to suffer to be a poet. Adolescence is enough
                                                                                                                  changing symptoms,” said Dr. Mackner.                         Do they have other types of behavioral problems? the
                             suffering for anyone.” but what if in addition to the normal awkwardness of
                                                                                                                                                                                other is social functioning: How are they getting along
                             adolescence, you are diagnosed with an illness that actually will last a lifetime?
                                                                                                                  So how has research into this condition shed light on         with friends? Do they have friends? Are they able to
                    laura Mackner, phd, an investigator in the center for biobehavioral Health at the             how adolescents adjust to chronic illness? therein we         participate in social activities at an age appropriate level?
                    Research institute at nationwide children’s Hospital, and wallace crandall, Md, Director      find the issue.                                               Are they able to attend school and do well?”
                    of the center for Pediatric and Adolescent inflammatory bowel Disease at nationwide
                                                                                                                  “When we first started investigating this area of research    Drs. Mackner and crandall studied the psychological
                                                                                                                  about five years ago, there was little research focusing on   and social aspects of adolescents with ibD in order to
                                                                                                                  the psychosocial aspects of ibD. there hasn’t been much
8 | research                                                                                                                                                                                                                      research | 9
understand whether                                                                               people sooner, like psycholo-     the inflammation of the intestine,” said Dr. crandall.          be used to help identify risk factors, especially during
   having the condition might                                                                       gists and social workers to try   “better control of stress could help with the psycho-           the first year of diagnosis, when the majority of disease
   affect psychosocial func-                                                                        to help patients with that ad-    social aspect, but could potentially help with disease          adjustment is expected to occur.
   tioning. What they found                                                                         justment process as opposed       control issues as well.”
                                                                                                                                                                                                      • The role of social functioning: Although preliminary
   was that adolescents with                                                                        to waiting until there is some
                                                                                                                                      Drs. crandall and Mackner would utilize behavioral              results show that ibD has an adverse impact on
   ibD have significantly fewer                                                                     crisis,” said Dr. crandall.
                                                                                                                                      measures to study patient stress levels, as well as             adolescent social functioning, more research needs to
   close friends than healthy
                                                                                                    identifying risk factors could    markers of inflammation at the bowel level to see               be done to clearly identify the extent of disease impact.
   adolescents and participate
                                                                                                    also help identify appropriate    if stressors predict flares in disease.                         Dr. Mackner identifies this as a vital need considering
   in fewer organized activi-
                                                                                                    treatment methods, such as                                                                        social functioning is so important during adolescence.
   ties. these results suggest                                                                                                        Dr. crandall would also like to investigate the genetic
                                                                                                    emphasizing coping strate-                                                                        “Adolescents’ social lives are very complex and we don’t
   that ibD has an adverse                                                                                                            components of stress as it relates to ibD. there are
                                                                                                    gies during therapy or group                                                                      yet know how ibD affects them or how to best help
   impact on adolescent social                                                                                                        normal variations within a gene known as polymor-
                                                                                                    intervention situations.                                                                          adolescents in this area,” said Dr. Mackner.
   functioning. this finding is                                                                                                       phisms that result in different effects. these gene
   important because research                                                                       So Much More to Learn             variations may influence the effect of stress on ibD.           • The role of medication: “one of the medications used
   has shown social function-                                                                       More studies need to be                                                                           to treat ibD is steroids and steroids have been associated
   ing among children is an                                                                                                           • The role of depression: “there is research that exists        with depression and emotional liability,” said Dr. Mackner.
                                                                                                    completed before the re-
   important predictor of                                                                                                             that shows that children with ibD have higher rates of          “they also are associated with aspects of adolescence
                                                                                                    search field is robust enough
   difficulties later in life.                                                                                                        depression than healthy kids,” said Dr. Mackner. “in the        that can be additionally stressful like weight gain and
                                                                                                    to start drawing conclusions
                                                                                                                                      past, we always thought that it was a reaction to having        increased acne.”
                                                                                                    about adolescent adjustment
   Drs. Mackner and crandall                                                                                                          this disease since it is a disease that is often embarrassing
                                                                                                    to chronic illness, especially
   believe that these differ-                                                                                                         to have.” However, new evidence suggests that there             • The role of age at disease onset: “A lot of the chronic
                                                                                                    adolescent adjustment in ibD.
   ences in social functioning                                                                                                        may be aspects of the inflammatory process that                 health conditions that have been studied from the
   may be attributed to the                                                                          “there are very few              actually contribute to the development of depression.           psychosocial research are ones that children are born
   fact that ibD is more of                                                                          researchers who focus on
   a stigmatized disease. “A                                                                         psychosocial issues in pedi-
   lot of diseases, for lack of                                                                      atric ibD,” said Dr. Mackner,            “If there is a way to know up front who is going to have difficulties
   better words, are socially                                                                        who believes there are only              down the line, we could involve the appropriate people sooner…”
   acceptable,” said Dr.                                                                             a few researchers in the
   crandall. “everybody                     “Kids with IBD have a stigmatizing
                                                                                                     nation doing so.
   understands asthma,                      disease. They don’t want to talk about                                                    future studies would involve looking specifically at the        with or acquire early in life,” said Dr. Mackner. “coping
   everybody understands                                                                             With continued funding,
                                            the symptoms because they can be                         Drs. crandall and Mackner
                                                                                                                                      role of pro-inflammatory cytokines in ibD. these proteins       mechanisms involved in this situation are vastly different
   cancer. if a kid with asthma                                                                                                       that are released by white blood cells have been found to       compared to being 13 and suddenly being diagnosed
   or cancer goes to school,                very embarrassing. It is a condition                     want not only to tackle the      be byproducts of both inflammation and depression.              with a chronic gastrointestinal disorder.” future research
   kids rally around them;                  that can be quite isolating.”                            unanswered questions that                                                                        would investigate how age at disease onset affects
   they don’t think they’re                                                                          their previous research has      “there is a substance known as tumor necrosis factor            psychosocial functioning in adolescence.
   going to catch it. kids with                                                                      raised, but also focus on the    alpha that is known to be an important contributor to
   ibD have a stigmatizing                                                                           bi-directional nature of ibD,    the inflammatory process in crohn’s disease,” said Dr.          even though Drs. Mackner and crandall have earmarked
   disease. they don’t want to                                                                       the relationship between         crandall. “Another one of its effects is causing a poor         these as areas that need further research, they probably
   talk about the symptoms because they can be very                                                  mind and body.                   appetite. So if a patient comes in and says ‘i’m tired;         won’t stop there. “Just being in the clinic and interacting
   embarrassing. it is a condition that can be quite isolating.”                                                                      i’ve been having trouble sleeping; i don’t want to eat,’        with ibD patients helps spark new research ideas,” said
                                                                  “Disease affects psychosocial factors and psychosocial factors      are they depressed or is it a symptom of the crohn’s            Dr. Mackner.
   Although they have identified the fact that social functioning affect disease,” said Dr. crandall. “When you’re treating one       disease?” Questions like these are of special importance
   may be impaired in patients with this condition, that’s just   of these things, you’re potentially treating both sides of the                                                                      What a good problem to have. More data would bring
                                                                                                                                      to an adolescent population since Drs. Mackner and
   half the battle. “the extent of the difficulties is unknown,”  equation. We need to continue research to tease out how                                                                             the health care field a little closer to providing new
                                                                                                                                      crandall think that kids with ibD who are more
   said Dr. Mackner.                                              much of it is a psychological effect and how much of it is a                                                                        answers to the question that Dr. crandall says is of
                                                                                                                                      depressed are going to have more problems with
                                                                  disease effect.”                                                                                                                    utmost importance.
                                                                                                                                      social functioning.
   learning more about the extent of the difficulties may
   help identify risk factors for this patient population. “once  To do so, they’d like to focus research on the                      • The role of the adjustment process: Drs. crandall and
                                                                                                                                                                                                      “How do adolescents adjust to chronic illness? the
   we identify risk factors, we’ll be able to identify which      following role players:                                             Mackner would like to develop a web-based program in
                                                                                                                                                                                                      answer is we don’t know, but we need to find out.”
   adolescents are likely to have problems in adjustment,”        • The role of stress: “there is some thought that stress            which adolescents with ibD would fill out questionnaires
                                                                  may affect the disease activity, rather than just the way                                                                           Further Reading: Mackner, lM.; crandall, Wv. “Psychological factors
   said Dr. Mackner.                                                                                                                  quarterly regarding stress, coping skills, social support       affecting pediatric inflammatory bowel disease.” Current Opinion in
                                                                  that patients deal with it. Stress does cause a physiologic         and disease activity during their first year of diagnosis.      Pediatrics, v. 19 issue 5, 2007, p. 548-52.
   “if there is a way to know up front who is going to have       response, but may cause one that actually increases                 this would help create a data entry system that could
   difficulties down the line, we could involve the appropriate


10 | research                                                                                                                                                                                                                                                               research | 11
Getting Cells to Tell                                                                                    are released, but these ions
                                                                                                                                  How do you get cells to tell                                                                             have to return to their “stor-
                                                                                                                                  you what is happening?                                                                                   age facility” before the cell
                                                                                                                                  first, you have to make                                                                                  can contract again. When the
                                                                                                                                  them feel at home.                                                                                       cell isn’t functioning properly,
                                                                                                                                                                                                                                           it takes longer for the calcium
                                                                                                                                  When an organ is housed                                                                                  ions to return, slowing the
                                                                                                                                  inside the human body, it                                                                                beating process, which is
                                                                                                                                  is exposed to blood, which                                                                               represented by a flattened
                                                                                                                                  serves as the major source of                                                                            out slope on the graph.
                                                                                                                                  energy. to extract cells from
                                                                                                                                  an organ outside of the body,                                                                            When Cells Tell of
                                                                                                                                  you must supply an energy                                                                                Heartbreaking News
                                                                                                                                  source. So the organ is “per-                                                                            the ability to show exactly
                                                                                                                                                                            These graphs show the shortening and the relength-
                                                                                                                                  fused” by being placed in a                                                                              what is going wrong within
                                                                                                                                                                            ening of a cardiac myocyte, a representation of its
                                                                                                                                  solution that is chemically                                                                              a cell is proving to be an
                                                                                                                                                                            “heartbeat.”
                                                                                                                                  representative of blood. “We                                                                             important part of disease
                                                                                                                                  try to trick them into think-                                                                            diagnosis. “What we’ve
                                                                                                                                  ing they’re still in the body                                                                            found is that the cells
                                                                                                                                                                                   motion and performs mathematical
                                                                                                                                  and still healthy, but they’re actually in                                                    respond similarly to the whole organ
                                                                                                                                                                                   conversions to represent the beat
                                                                                                                                  a dish in an incubator in artificial fluid,”                                                  and the whole organism,” said Dr.
                                                                                                                                                                                   graphically, similar to the graph of a
                                                                                                                                  said Dr. Wold. this artificial fluid also                                                     Wold. once you get cells in the mood
                                                                                                                                                                                   heart monitor. investigators can then
                                                                                                                                  contains an enzyme that breaks apart                                                          to communicate, they have plenty
                                                                                                                                                                                   analyze the slopes on the graph to
                                                                                                                                  all of the scaffolding around the cells.                                                      to say about heart harming disease,
                                                                                                                                                                                   determine whether or not the beating
                                                                                                                                  once the cells are exposed at their                                                           including type 2 diabetes.
                                                                                                                                                                                   cell is functioning properly.
                                                                                                                                  rawest level, they are “suspended,” a
                                                                                                                                                                                                                                As opposed to type 1 diabetes, in
                                                                                                                                  process that leaves them unattached              if the graphical results reveal that the
                                                                                                                                                                                                                                which a malfunctioning immune
                                                                                                                                  and floating in a special liquid bath.           cell is not functioning properly, it is
                                                                                                                                                                                                                                system doesn’t allow the pancreas to
                                                                                                                                                                                   time to find out why. one way is by
                                                                                                                                  now the real, nitty gritty investigation                                                      produce insulin, the pancreas of a type
                                                                                                                                                                                   looking at molecules involved in cell
                                                                                                                                  can begin.                                                                                    2 diabetic creates plenty of insulin, but



   Listening to the Heart
                                                                                                                                                                                   signaling. “cell signaling is the way
                                                                                                                                                                                                                                the body stops reacting to it properly.
                                                                                                                                  “cardiac myocytes actually beat when             a cell communicates within itself and
                                                                                                                                                                                                                                this malfunction can lead to serious
                                                                                                                                  stimulated, just like the heart does.            with other cells,” said Dr. Wold. one
                                                                                                                                                                                                                                impacts on many systems of the body,
                                                                                                                                  that’s what makes up the                         of the cell signaling molecules of most
                                                                                                                                                                                                                                                including the heart.
                                                                                                                                  mechanics of the heart,”
   inSigHt fRoM tHe HeARt’S SMAlleSt MeSSengeRS                                                                                   said Dr. Wold.                      studying disease at the cellular level doesn’t                            “the main killer of
   ReveAlS eARlY WARningS of HeARt DiSeASe                                                                                                                           only help identify what doesn’t work for the                               diabetics is heart
                                                                                                                                  to get the cells to beat,                                                                                     disease. Most people
                                                                                                                                  more coaxing is required.             heart, but also what does work, including

   W
               hen’s the last time you         fist-sized organ is responsible for      heart muscle, it has a story to tell.                                                                                                                   think that if diabetics
               talked to yourself? the truth   one of the most vital life functions,    that is, if you’re listening.
                                                                                                                                  “We use a device that                therapeutic interventions like medication.                               take their medicine,
                                                                                                                                  stimulates the cell in
               is you’re doing it right now.   pumping oxygen-rich blood through                                                                                                                                                                they’ll be fine, but that’s
                                                                                        loren e. wold, phd, is listening. As      the same way that the                            interest to Dr. Wold is the calcium ion
                                               blood vessels to reach the rest of the                                                                                                                                           not the case,” said Dr. Wold.
   cells in the human body are living                                                   a principal investigator in the center    nervous system would stimulate the               because it regulates contraction and
                                               body. Although we are most used to                                                 heart to contract,” said Dr. Wold. While                                                      When type 2 diabetes is investigated at
   gossip mills. Sending and receiving                                                  for cardiovascular Medicine at the                                                         relaxation of the cell.
                                               listening to this big communicator                                                 this superfusion/stimulation chamber,                                                         the cellular level, the slope representing
   chemical messages along neural                                                       Research institute at nationwide
                                               with a stethoscope, research is                                                    which looks like a shallow, cylindrical          Just like when the heart beats, there        the relaxation phase of the heart beat
   pathways, firing synapses, exchang-                                                  children’s Hospital, Dr. Wold is
                                               showing that it’s worth getting                                                    dish with horizontal, metallic prongs            are two phases involved when the cell        is flattened out more than it would be
   ing gasses and elements, regulating                                                  studying heart function by taking a
                                               another perspective when it comes                                                  pointing inward, makes the cell beat,            beats. the cell squeezes together            in a healthy cell. this means that the
   temperature and cellular growth,                                                     big look at the smallest of parts.
                                               to studying heart disease.                                                         investigators view the cell through a            during a contraction phase and then          heart muscle is weakened for some
   your body is in constant conversation
                                                                                        “in order to understand cardiology, you   specialized microscope that captures             returns to resting state (relaxation         reason, which impacts the functioning
   with itself.                                Down at the cellular level lives the
                                                                                        need to understand what is happening      images of the beating in real time. A            phase) before it can contract again.         of the whole heart.
                                               cardiac myocyte, the heart’s smallest
   of all of the body’s conversationalists,                                             at the cell level,” said Dr. Wold.        program then analyzes the cell’s                 When the cell contracts, calcium ions
                                               messenger. Although it is simply a
   the heart is one of the biggest. this
                                               microscopic cell extracted from the

12 | research                                                                                                                                                                                                                                               research | 13
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reSearch Magazine Issue 1

  • 1. listening to the heart’s smallest messenger How this device gets cells to tell research A PublicAtion of The ReseaRch InsTITuTe aT naTIonwIde chIldRen’s hospITal
  • 2. research is dedicated to the mission of informing and inspiring readers by highlighting scientific table of contents a message from the president performance at the Research institute at nationwide children’s Hospital. this publication is produced biannually by the Marketing and Public Relations Department at nationwide children’s Hospital. Dear Friends and Colleagues: One of the prevailing joys of being a scientist is the knowledge that each day could fe at ure s be a day of fascination and revelation. The intellectual pursuit of a life-altering 4 wanted: a Generation of Quitters discovery, particularly one that could improve the life of a child, drives us to brady Reynolds, PhD, has never smoked a cigarette in his life. continue our years of research. Yet most of his day is spent trying to find ways to quit. Our excitement and fascination shouldn’t stay within our walls. We want to share le a deRs hIp 8 The Importance of studying adolescents these experiences with you. So welcome to our first issue of reSearch. The Research Institute at What if in addition to the normal awkwardness of adolescence, nationwide children’s hospital you are diagnosed with an illness that will last a lifetime? findings Within these pages, you will discover how impulsive thought processes affect a teen’s John a. Barnard, Md suggest that adolescents shouldn’t be treated like adults, but they President ability to quit smoking; be privy to the way heart cells “communicate” and what they shouldn’t be treated like children either. lauren o. Bakaletz, phd say about heart disease; and be revealed to the world of an adolescent facing a chronic Vice President, Basic Sciences Research Kelly Kelleher, Md, Mph 12 listening to the heart GI illness, and how we are searching for the ideal ways to treat this condition. Vice President, Health Services Research Down at the cellular level lives the cardiac myocyte, the heart’s smallest messenger. Although it is simply a microscopic cell extracted Join us in our enthusiasm for the future of pediatric research and in the milestones Grant Morrow III, Md Medical Director from the heart muscle, it has a story to tell. that is, if you’re listening. – sometimes incremental and sometimes monumental – we reach each day in our daniel R. Mann pursuit of discovery. Vice President, Research Administration and Operations e xt ras Katherine s. Milem Vice President, Research Business Services 7 noteworthy news about the Research institute and its faculty. research Writer and editor 16 Into the Future John Barnard, Md Melissa hamilton President the look of Research in 2012. the Research institute at nationwide children’s Hospital Designer Tanya Bender Professor of Pediatrics Photographers o n tHe co v eR the ohio State university college of Medicine Brad smith dan smith Loren E. Wold, PhD, examines a device used to study the function of heart muscle cells, a tool that could change the way science understands heart disease. Manager, Research communications Jan arthur contact us at ResearchMagazine@nationwidechildrens.org research | 3
  • 3. to complete the eDt, the participant views a computer screen that displays two monetary amounts, one that offers a smaller immediate reward and another that offers the possibility of a larger reward at a delayed time. for example, do you want 15 cents now or the possibility of 30 cents 28 seconds from now? if the participant clicks the Wanted: computer to choose 15 cents now, coins come clinking out of a specialized change machine that is connected to Brady Reynolds, PhD, demonstrates the computer. the Experiential Discounting Task. “that’s why it’s called the experiential a Generation of Quitters Discounting task. Participants actually experience the choice they make at that moment,” said Dr. Reynolds. the program at nationwide children’s in January of 2006, one of the first- and-only smoking cessation programs these findings have implications for designing effective smoking cessation programs. “A person who discounts HoW ReSeARcH iS finDing neW WAYS to HelP ADoleScentS Quit SMoking for adolescents in central ohio. most by delay is someone whose B if the participant instead chooses 30 behavior is led by more immediate rady Reynolds, phd, has to smoke into adulthood, practically a larger reward that is delayed for a cents, they have to wait a set period of Adolescents who enroll in this pro- consequences. to reach an adoles- never smoked a cigarette guaranteeing increased health risks, period of time. Delay discounting has time to see if they will actually receive gram attend a smoking cessation cent smoker who discounts a great in his life. Yet most of his since approximately half of people been shown to play an important role the money, since the delayed option class held at nationwide children’s deal, you need to make the benefits day is spent trying to find who smoke are expected to die from in cigarette smoking behavior. may not actually pay out each time. main campus once a week for 10 of quitting smoking more immediate. ways to quit. smoking-related illnesses, according this time delay can vary from zero weeks. During the first half of the Programs that stress the long-term to further understand this relation- seconds, 7 seconds, 14 seconds, to program, participants are taught to the World Health organization. effects of smoking are going to be less You won’t see him crunching on a ship, Dr. Reynolds has developed a 28 seconds. After the time delay, the health and smoking education effective for these piece of nicotine gum or slapping on Although adolescent smokers often delay discounting task that he believes selected money adolescents,” said nicotine patches. instead, you’ll find continue their habit into adulthood, overcomes some of the shortcomings amount appears “That’s why it’s called the experiential discounting Dr. Reynolds. him crunching numbers and trying it may not always be clearly by of previously developed methods. in the computer’s to patch holes in research about what choice. Sixty-one percent of adoles- “bank account” Task. participants actually experience the choice Although Dr. Most delay discounting tasks ask motivates adolescents to quit smoking. cents report wanting to quit smoking participants to choose between that will be cashed they make at that moment,” said dr. Reynolds. Reynolds is quick cigarettes and 59 percent report a out once the par- to suggest his that’s because as a principal investi- hypothetical situations, such as, quit attempt in the past year. ticipant has completed the entire task. including the common myths of findings could be applied to current gator in the center for biobehavioral would you prefer $10 now or $100 smoking. class five is the required smoking cessation programs, he says Health at the Research institute at So why can’t they just quit? that’s one year from now. but according to every time the participant chooses “smoking quit date” for participants that even the best of research needs to nationwide children’s Hospital Dr. what Dr. Reynolds wants to find out. Dr. Reynolds, this hypothetical method the smaller, immediate amount, that and the remaining sessions are used be strengthened by further evidence. Reynolds is using research techniques can be tricky for adolescents. quantity goes down for the next choice As a behavioral psychologist, Dr. as a support group to help deal with that’s why he has made the eDt to learn how to help adolescents (the next option may give you 10 Reynolds has spent his career trying “because adolescents, particularly withdrawal and lifestyle changes available via the web for behavioral become quitters. cents). this calculation helps provide a to understand what motivates people younger adolescents, aren’t as psycho- associated with quitting smoking. laboratories throughout the world. clearer measure of delay discounting. other investigators can access the “Adolescence is a sensitive period to to certain behaviors. Although some logically developed in many ways as those who chose the smaller, immedi- Participants of the n-o-t program at begin smoking,” said Dr. Reynolds. motivators tied to cigarette smoking adults; they perceive information differ- software, purchase the appropriate ate reward more often than the larger, nationwide children’s Hospital can have already been identified, such as ently,” said Dr. Reynolds. “for example, coin machine and conduct their own According to surveillance by the delayed option are described as being choose whether or not they want to impulsivity, there is still a lot to learn. they don’t seem to understand the con- experiential delay discounting studies. Morbidity and Mortality Weekly Report, more impulsive discounters. perform the delay discounting task cept of time (like a year) as adults do.” Dr. Reynolds will then analyze their approximately 2,000 adolescents “impulsivity is not described by one along with their participation in the to determine how delay discounting findings from the eDt, in hopes that initiate smoking each day. that means type of behavior. it is multifaceted,” that’s why Dr. Reynolds developed 10-week program. Dr. Reynolds’ delay relates to cigarette smoking behavior, they can also help shape smoking that every minute, an adolescent is said Dr. Reynolds. the experiential Discounting task discounting studies with this adolescent the eDt is being evaluated with an cessation and education programs trying a cigarette for the first time. (eDt), a computer-based program smoking population have shown that A recently studied aspect of impulsivity adolescent smoking cessation program for adolescents. that measures delay discounting by the adolescents who discount more And that first time may not be the is delay discounting. Delay discount- called not-on-tobacco (n-o-t), the often are those who are less likely to More Smoke Signals requiring participants to choose last. Studies show that the majority of ing describes an individual’s preference official teen smoking cessation quit smoking, even after participating the eDt is not the only method between moment-in-time situations as adolescents who smoke daily continue for a smaller, immediate reward over program of the American lung in the n-o-t program. Dr. Reynolds is using to understand opposed to hypothetical situations. Association. Dr. Reynolds initiated 4 | research research | 5
  • 4. Circulatory System Could Provide New Strategy for Mus- cular Dystrophy Gene Therapy Future Study to Monitor Medication Usage and Effects Technique Helps Diagnose Asthma Attacks Circulatory System Could Provide New Strategy for Muscular Dystrophy Gene Therapy Future Study to Monitor Medication Usage and Effects Tech- nique noteworthy | Helps Diagnose Asthma Attacks Circulatory Sys- tHe ReSeARcH inStitute At nAtionWiDe cHilDRen’S HoSPitAl Circulatory System Could Provide the system alerts a trained psychiatric nurse to contact the New Strategy for Muscular Dystrophy patient or parent and when necessary, contact the patient’s Gene Therapy physician or hospital emergency services. preliminary results have shown that the participants Although Dr. Reynolds would like to investigators at the Research institute have delve into these new areas of research, the PhaSt project could provide medication monitoring in significantly maintained abstinence from smoking received an $8.1 million grant from the he is not abandoning the eDt. in fact, instances when families or the overstretched child mental national institutes of Health to learn more when they were being paid, even during a period at fellow principal investigators at the about strategies to treat muscular dystrophy, potentially health systems do not have the resources to follow the Research institute have plans to use it recommended–often weekly–physician visits. the end of the program when it didn’t matter how leading to two new gene therapy approaches. the primary to determine the role delay discounting research strategy will use the circulatory system for gene much they smoked. plays in behaviors beyond smoking delivery of the dystrophin gene, as opposed to direct the study is expected to begin in early 2008 and continue through 2010. initial funding for the study was made cessation. Planned studies include injections into individual muscles. this vascular delivery smoking behavior. Working with program style would encourage possible by a collaborative grant between nationwide measuring suicidal impulsivity and strategy provides a more favorable opportunity for collaborators, he is collecting data from maintenance by providing the needed children’s and the ohio State university. studying what makes people likely to correction of lost function throughout the body reaching a web-based contingency management peer support group,” said Dr. Reynolds. use safety equipment, such as sports many muscles, as well as the heart. Study Helps Differentiate Between program. Participants of this program safety equipment or parent use of infant until then, the n-o-t program Asthma and Vocal Chord Dysfunction are asked to record “video diaries” of car seats and home smoke alarms. Two Centers of Emphasis Obtain continues to make an impact. of the Doctors at nationwide children’s Hospital themselves three times a day using web Leadership more than 60 adolescents who have performed a clinical study using spirometry cameras. At the time of each “diary even though Dr. Reynolds’ original Bill smoyer, Md, Robert c. kelsch chair participated in the n-o-t program at in the emergency Department to identify entry” they blow into a picometer, a plans for the eDt were focused on of Pediatric nephrology at the university nationwide children’s, 25 percent adolescents who had findings suggestive device used to measure carbon adolescents, his findings may have of Michigan, has been appointed director made a significant decrease in smoking of vocal chord dysfunction (vcD) compared to an acute monoxide levels, a distinct marker implications for adult smokers. “the of the center for clinical and translational frequency and many of the others asthma attack. the manuscript was published in the July of how much tobacco someone has research would have to be explored, but Research at the Research institute. Dr. Smoyer will work report at least some decrease. issue of Pediatric Pulmonology. smoked in the past three to six hours. there are indications that these findings to orchestrate further development of clinical and Participants are given money for Genetic Contributions may apply to the adult population since translational research across the organization. According to the study, 12 of the 17 adolescents who continued abstinence during the beyond his current research methods, research has already shown that adult presented to the emergency Department with difficulty treatment phases. Dr. Reynolds would like to further the smokers discount more than adult After serving in an interim position, breathing, but with high normal oxygen levels, were understanding of adolescent smoking non-smokers,” he said. leif nelin, Md, has been appointed found to have evidence of vcD on spirometry. this led Preliminary results have shown that the director of the center for Perinatal cessation by investigating how genetics to a change in the therapy for these patients. Spirometry participants significantly maintained for now, however, Dr. Reynolds plans Research at the Research institute. contribute to smoking habits. He and used in the acute setting of difficulty breathing can help abstinence from smoking when they to focus his research on ways to help Dr. nelin plans to continue to improve chris bartlett, PhD, principal investiga- differentiate vcD from asthma attacks. were being paid, even during a period adolescents specifically. “if we can the integration between the center for tor in the center for Quantitative and change smoking habits during at the end of the program when it Perinatal Research and the Division of neonatology, the study suggests that if more emergency departments computational biology at the Research adolescence, we’ll be able to greatly didn’t matter how much they smoked. an ability he demonstrated during his interim position. made use of the spirometry test, it could cut down on the institute, are already collecting pilot data reduce the long-term effects of number of children who are misdiagnosed and potentially With continued funding, Dr. Reynolds that involves isolating genes associated smoking,” said Dr. Reynolds. Future Study to Monitor Medication hospitalized. hopes to maintain this method of with different neural systems in the Usage and Effects research with the hopes of one day brain (many of which are associated For more information about the A research study is planned to trial a combining the contingency manage- with addiction) to search for genetic not-on-Tobacco program at new technology that helps monitor how ment model with the n-o-t program markers of delay discounting. nationwide children’s hospital, medications, specifically anti-depressants, model, for a more comprehensive call (614) 355-3445, or click on are used in children and teens. other hopeful genetic studies include “education classes” at smoking cessation course. investigating recent research in the field nationwidechildrens.org. the project, named “PhaSt”, or Pharmaceutical Safety “by reinforcing positive behavior, that suggests the relationship between tracking: Managing Medications for Patient Safety, involves Learn about more research the contingency management portion smoking behavior in parents and their Further Reading: Reynolds, b.; Patak, M.; Shroff, an interactive voice response telephone system to contact news and highlights at could help kids get through the children can most likely be accounted P. “Adolescent smokers rate delayed rewards as less parents or teenage patients. the system requires simple yes withdrawal stage that is common for by their genetic relatedness, not just certain than adolescent nonsmokers.” Drug and Alcohol Dependence, v. 90 issue 2-3, 2007, p. 301-3. or no answers to questions about the medications and their NationwideChildrens.org/research. with the early days of smoking by a child mimicking parental behavior. side effects. When a parent or patient indicates a problem, cessation. then combining the n-o-t 6 | research research | 7
  • 5. “IBD is an ideal disease for investigating adolescent adjustment to chronic illness, given its adolescent onset, and embarrassing, socially limiting, and appearance-changing symptoms.” children’s Hospital, are studying adolescents to better research on adolescent adjustment to other conditions, understand how this patient population adjusts to either,” said Dr. Mackner. chronic illness. overall, a comprehensive adolescent perspective is lacking. Although their research might not be poetic, what their “the research on psychosocial adjustment to pediatric findings suggest seems to be worth writing home about: chronic illness has focused primarily on children. if adoles- adolescents shouldn’t be treated like adults, but they cents are included in this research, they are often included shouldn’t be treated like children either. in the same sample with younger children. even when adolescents are the focus, development issues are often The Uniqueness of Adolescence not taken into account,” said Dr. Mackner. Adolescence involves more changes than any developmental period other than infancy. When Drs. Mackner and crandall refer to adolescents, they mean those age 11 through 18, since this is the period these years are wrought with extreme biological changes when most changes in psychosocial adjustment appear. including raging hormones, acne, and increased body So, why should an 11-year-old be categorized separately odor and body hair. from an 8-year-old? When it comes to psychosocial on top of the stressors normally associated with adoles- development, adolescence and childhood are worlds cence, imagine having an incurable condition in which apart. Adolescents spend significantly more time with your main symptoms include diarrhea, rectal bleeding, their peers than children do. close friends begin to abdominal pain and delayed puberty. surpass parents as a primary source of social support and Wallace Crandall, MD and Laura Mackner, PhD acceptance by peers plays an important part of adolescent inflammatory bowel diseases (ibDs) such as crohn’s self-identity. involvement in extracurricular activities disease and ulcerative colitis are chronic conditions in contributes not only to acceptance by peers, but also The Importance of which inflammation in the intestines can result in these takes on an important role for those planning to apply sometimes embarrassing symptoms. Although ibD has to college. in addition, the development of romantic typically been viewed in the medical community as an relationships becomes a significant focus. Studying Adolescents adult disease, about 25 percent of ibD cases occur in the pediatric population, with the majority beginning their onset in adolescence. Adjusting to the normal changes adolescence brings is tough enough; adolescents with When Illness Adds Insult to Injury With so many aspects of psychosocial development how do you study whether or not an adolescent is adjusting well to this new stage of life? Researchers work to understand chronic ibD are given even more to adjust to. Illness in a neglected Field of study “ibD is an ideal disease for investigating adolescent “there are two main aspects of studying psychosocial adjustment to chronic illness, given its adolescent onset, functioning,” said Dr. Mackner. “one is psychological A and embarrassing, socially limiting, and appearance- functioning: Are they depressed? Do they have anxiety? poet once remarked, “You don’t have to suffer to be a poet. Adolescence is enough changing symptoms,” said Dr. Mackner. Do they have other types of behavioral problems? the suffering for anyone.” but what if in addition to the normal awkwardness of other is social functioning: How are they getting along adolescence, you are diagnosed with an illness that actually will last a lifetime? So how has research into this condition shed light on with friends? Do they have friends? Are they able to laura Mackner, phd, an investigator in the center for biobehavioral Health at the how adolescents adjust to chronic illness? therein we participate in social activities at an age appropriate level? Research institute at nationwide children’s Hospital, and wallace crandall, Md, Director find the issue. Are they able to attend school and do well?” of the center for Pediatric and Adolescent inflammatory bowel Disease at nationwide “When we first started investigating this area of research Drs. Mackner and crandall studied the psychological about five years ago, there was little research focusing on and social aspects of adolescents with ibD in order to the psychosocial aspects of ibD. there hasn’t been much 8 | research research | 9
  • 6. understand whether people sooner, like psycholo- the inflammation of the intestine,” said Dr. crandall. be used to help identify risk factors, especially during having the condition might gists and social workers to try “better control of stress could help with the psycho- the first year of diagnosis, when the majority of disease affect psychosocial func- to help patients with that ad- social aspect, but could potentially help with disease adjustment is expected to occur. tioning. What they found justment process as opposed control issues as well.” • The role of social functioning: Although preliminary was that adolescents with to waiting until there is some Drs. crandall and Mackner would utilize behavioral results show that ibD has an adverse impact on ibD have significantly fewer crisis,” said Dr. crandall. measures to study patient stress levels, as well as adolescent social functioning, more research needs to close friends than healthy identifying risk factors could markers of inflammation at the bowel level to see be done to clearly identify the extent of disease impact. adolescents and participate also help identify appropriate if stressors predict flares in disease. Dr. Mackner identifies this as a vital need considering in fewer organized activi- treatment methods, such as social functioning is so important during adolescence. ties. these results suggest Dr. crandall would also like to investigate the genetic emphasizing coping strate- “Adolescents’ social lives are very complex and we don’t that ibD has an adverse components of stress as it relates to ibD. there are gies during therapy or group yet know how ibD affects them or how to best help impact on adolescent social normal variations within a gene known as polymor- intervention situations. adolescents in this area,” said Dr. Mackner. functioning. this finding is phisms that result in different effects. these gene important because research So Much More to Learn variations may influence the effect of stress on ibD. • The role of medication: “one of the medications used has shown social function- More studies need to be to treat ibD is steroids and steroids have been associated ing among children is an • The role of depression: “there is research that exists with depression and emotional liability,” said Dr. Mackner. completed before the re- important predictor of that shows that children with ibD have higher rates of “they also are associated with aspects of adolescence search field is robust enough difficulties later in life. depression than healthy kids,” said Dr. Mackner. “in the that can be additionally stressful like weight gain and to start drawing conclusions past, we always thought that it was a reaction to having increased acne.” about adolescent adjustment Drs. Mackner and crandall this disease since it is a disease that is often embarrassing to chronic illness, especially believe that these differ- to have.” However, new evidence suggests that there • The role of age at disease onset: “A lot of the chronic adolescent adjustment in ibD. ences in social functioning may be aspects of the inflammatory process that health conditions that have been studied from the may be attributed to the “there are very few actually contribute to the development of depression. psychosocial research are ones that children are born fact that ibD is more of researchers who focus on a stigmatized disease. “A psychosocial issues in pedi- lot of diseases, for lack of atric ibD,” said Dr. Mackner, “If there is a way to know up front who is going to have difficulties better words, are socially who believes there are only down the line, we could involve the appropriate people sooner…” acceptable,” said Dr. a few researchers in the crandall. “everybody “Kids with IBD have a stigmatizing nation doing so. understands asthma, disease. They don’t want to talk about future studies would involve looking specifically at the with or acquire early in life,” said Dr. Mackner. “coping everybody understands With continued funding, the symptoms because they can be Drs. crandall and Mackner role of pro-inflammatory cytokines in ibD. these proteins mechanisms involved in this situation are vastly different cancer. if a kid with asthma that are released by white blood cells have been found to compared to being 13 and suddenly being diagnosed or cancer goes to school, very embarrassing. It is a condition want not only to tackle the be byproducts of both inflammation and depression. with a chronic gastrointestinal disorder.” future research kids rally around them; that can be quite isolating.” unanswered questions that would investigate how age at disease onset affects they don’t think they’re their previous research has “there is a substance known as tumor necrosis factor psychosocial functioning in adolescence. going to catch it. kids with raised, but also focus on the alpha that is known to be an important contributor to ibD have a stigmatizing bi-directional nature of ibD, the inflammatory process in crohn’s disease,” said Dr. even though Drs. Mackner and crandall have earmarked disease. they don’t want to the relationship between crandall. “Another one of its effects is causing a poor these as areas that need further research, they probably talk about the symptoms because they can be very mind and body. appetite. So if a patient comes in and says ‘i’m tired; won’t stop there. “Just being in the clinic and interacting embarrassing. it is a condition that can be quite isolating.” i’ve been having trouble sleeping; i don’t want to eat,’ with ibD patients helps spark new research ideas,” said “Disease affects psychosocial factors and psychosocial factors are they depressed or is it a symptom of the crohn’s Dr. Mackner. Although they have identified the fact that social functioning affect disease,” said Dr. crandall. “When you’re treating one disease?” Questions like these are of special importance may be impaired in patients with this condition, that’s just of these things, you’re potentially treating both sides of the What a good problem to have. More data would bring to an adolescent population since Drs. Mackner and half the battle. “the extent of the difficulties is unknown,” equation. We need to continue research to tease out how the health care field a little closer to providing new crandall think that kids with ibD who are more said Dr. Mackner. much of it is a psychological effect and how much of it is a answers to the question that Dr. crandall says is of depressed are going to have more problems with disease effect.” utmost importance. social functioning. learning more about the extent of the difficulties may help identify risk factors for this patient population. “once To do so, they’d like to focus research on the • The role of the adjustment process: Drs. crandall and “How do adolescents adjust to chronic illness? the we identify risk factors, we’ll be able to identify which following role players: Mackner would like to develop a web-based program in answer is we don’t know, but we need to find out.” adolescents are likely to have problems in adjustment,” • The role of stress: “there is some thought that stress which adolescents with ibD would fill out questionnaires may affect the disease activity, rather than just the way Further Reading: Mackner, lM.; crandall, Wv. “Psychological factors said Dr. Mackner. quarterly regarding stress, coping skills, social support affecting pediatric inflammatory bowel disease.” Current Opinion in that patients deal with it. Stress does cause a physiologic and disease activity during their first year of diagnosis. Pediatrics, v. 19 issue 5, 2007, p. 548-52. “if there is a way to know up front who is going to have response, but may cause one that actually increases this would help create a data entry system that could difficulties down the line, we could involve the appropriate 10 | research research | 11
  • 7. Getting Cells to Tell are released, but these ions How do you get cells to tell have to return to their “stor- you what is happening? age facility” before the cell first, you have to make can contract again. When the them feel at home. cell isn’t functioning properly, it takes longer for the calcium When an organ is housed ions to return, slowing the inside the human body, it beating process, which is is exposed to blood, which represented by a flattened serves as the major source of out slope on the graph. energy. to extract cells from an organ outside of the body, When Cells Tell of you must supply an energy Heartbreaking News source. So the organ is “per- the ability to show exactly These graphs show the shortening and the relength- fused” by being placed in a what is going wrong within ening of a cardiac myocyte, a representation of its solution that is chemically a cell is proving to be an “heartbeat.” representative of blood. “We important part of disease try to trick them into think- diagnosis. “What we’ve ing they’re still in the body found is that the cells motion and performs mathematical and still healthy, but they’re actually in respond similarly to the whole organ conversions to represent the beat a dish in an incubator in artificial fluid,” and the whole organism,” said Dr. graphically, similar to the graph of a said Dr. Wold. this artificial fluid also Wold. once you get cells in the mood heart monitor. investigators can then contains an enzyme that breaks apart to communicate, they have plenty analyze the slopes on the graph to all of the scaffolding around the cells. to say about heart harming disease, determine whether or not the beating once the cells are exposed at their including type 2 diabetes. cell is functioning properly. rawest level, they are “suspended,” a As opposed to type 1 diabetes, in process that leaves them unattached if the graphical results reveal that the which a malfunctioning immune and floating in a special liquid bath. cell is not functioning properly, it is system doesn’t allow the pancreas to time to find out why. one way is by now the real, nitty gritty investigation produce insulin, the pancreas of a type looking at molecules involved in cell can begin. 2 diabetic creates plenty of insulin, but Listening to the Heart signaling. “cell signaling is the way the body stops reacting to it properly. “cardiac myocytes actually beat when a cell communicates within itself and this malfunction can lead to serious stimulated, just like the heart does. with other cells,” said Dr. Wold. one impacts on many systems of the body, that’s what makes up the of the cell signaling molecules of most including the heart. mechanics of the heart,” inSigHt fRoM tHe HeARt’S SMAlleSt MeSSengeRS said Dr. Wold. studying disease at the cellular level doesn’t “the main killer of ReveAlS eARlY WARningS of HeARt DiSeASe only help identify what doesn’t work for the diabetics is heart to get the cells to beat, disease. Most people more coaxing is required. heart, but also what does work, including W hen’s the last time you fist-sized organ is responsible for heart muscle, it has a story to tell. think that if diabetics talked to yourself? the truth one of the most vital life functions, that is, if you’re listening. “We use a device that therapeutic interventions like medication. take their medicine, stimulates the cell in is you’re doing it right now. pumping oxygen-rich blood through they’ll be fine, but that’s loren e. wold, phd, is listening. As the same way that the interest to Dr. Wold is the calcium ion blood vessels to reach the rest of the not the case,” said Dr. Wold. cells in the human body are living a principal investigator in the center nervous system would stimulate the because it regulates contraction and body. Although we are most used to heart to contract,” said Dr. Wold. While When type 2 diabetes is investigated at gossip mills. Sending and receiving for cardiovascular Medicine at the relaxation of the cell. listening to this big communicator this superfusion/stimulation chamber, the cellular level, the slope representing chemical messages along neural Research institute at nationwide with a stethoscope, research is which looks like a shallow, cylindrical Just like when the heart beats, there the relaxation phase of the heart beat pathways, firing synapses, exchang- children’s Hospital, Dr. Wold is showing that it’s worth getting dish with horizontal, metallic prongs are two phases involved when the cell is flattened out more than it would be ing gasses and elements, regulating studying heart function by taking a another perspective when it comes pointing inward, makes the cell beat, beats. the cell squeezes together in a healthy cell. this means that the temperature and cellular growth, big look at the smallest of parts. to studying heart disease. investigators view the cell through a during a contraction phase and then heart muscle is weakened for some your body is in constant conversation “in order to understand cardiology, you specialized microscope that captures returns to resting state (relaxation reason, which impacts the functioning with itself. Down at the cellular level lives the need to understand what is happening images of the beating in real time. A phase) before it can contract again. of the whole heart. cardiac myocyte, the heart’s smallest of all of the body’s conversationalists, at the cell level,” said Dr. Wold. program then analyzes the cell’s When the cell contracts, calcium ions messenger. Although it is simply a the heart is one of the biggest. this microscopic cell extracted from the 12 | research research | 13