Medical research slideshare_march 12_2015

MedicalResearch.com
Exclusive Interviews with Medical Research and
Health Care Researchers from Major and Specialty Medical
Research Journals and Meetings
Editor: Marie Benz, MD
info@medicalresearch.com
March 11 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Hepatocyte Growth Factor May Improve Painful Diabetic Neuropathy
MedicalResearch.com Interview with:
Dr. John A Kessler MD
The Ken and Ruth Davee Professor of Stem Cell Biology Department of Neurology Professor, Department of Pharmacology
Northwestern University Feinberg School of Medicine
• Medical Research: What is the background for this study? What are the main findings?
Dr. Kessler: Painful diabetic neuropathy afflicts millions of patients. It interferes with sleep
and many daily activities of living, and predisposes to depression.
• There is a loss of sensation in the legs which predisposes to foot/leg ulcers which may lead to
amputation.
• The only currently available treatments, other than controlling glucose levels, are drugs
including gabapentin, pregabalin, or antidepressants which have major side effects and which
help only some patients.
• These are medications which must be taken daily or several times daily and are often poorly
tolerated by patients.
• This study examined the effects of a nonviral gene therapy approach for using hepatocyte
growth factor (HGF) to treat patients with painful diabetic neuropathy. HGF helps to support
the health of neurons and it also helps to grow new blood vessels to support nerve function.
• Patients received two sets of treatments (injections) and were then followed for 9
months. The treatment was exceptionally well tolerated – literally without significant side
effects.
• The patients had highly significant reductions in pain and improvement in the quality of life,
and their ability to sense gentle pressure (touch) was improved. The benefits lasted months
without additional treatment.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

• Medical Research: What should clinicians and patients take away from your report?
• Dr. Kessler: Hepatocyte growth factor gene therapy may provide a treatment that not only
reduces symptoms and improves quality of life but also may help to regenerate nerve
function.
• No other such potentially regenerative treatments have ever been available.
• The percentage of patients whose symptoms improved exceeded what has generally been
reported for any other treatments.
• If the findings are further substantiated in a planned large phase 3 study, this will be the first
regenerative therapy for the nervous system.

• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Kessler: A planned phase 3 study will seek to make this an approved therapy that will be
widely available.
• Future studies will help to determine whether retreatments with hepatocyte growth factor
will lead to actual cure of aspects of the nerve damage rather than just relief of symptoms.
• Citation:
• John A. Kessler, A. Gordon Smith, Bong-Soo Cha, Sung Hee Choi, James Wymer, Aziz Shaibani,
Senda Ajroud-Driss. Double-blind, placebo-controlled study of HGF gene therapy in diabetic
neuropathy. Annals of Clinical and Translational Neurology, 2015; DOI: 10.1002/acn3.186

Nuts May Lower Odds Of Metabolic Syndrome In Adolescents
Dr. Roy Kim, MD
Depts. Endocrinology and Pediatrics
UT Southwestern Medical Center
• Medical Research: What was the problem you were focused on?
• Dr. Kim: We were focused on the problem of adolescent metabolic syndrome, a major public
health problem. Our objective was to determine whether nut intake is linked with any
difference in odds for metabolic syndrome in US adolescents.
• Medical Research: How is metabolic syndrome defined?
• Dr. Kim: In general it is diagnosed when there are 3 or more of the following things:
increased belly fat, high blood pressure, high fasting glucose, elevated triglycerides, and low
HDL cholesterol.
• Medical Research: How did you do your study?
• Dr. Kim: We used data from the National Health and Nutrition Examination Survey (NHANES),
years 2003-2010, to examine health status and the diet history for 2,322 US adolescents age
12 to 19 years.

Dr. Roy Kim, MD
• Dr. Kim: Our first major finding was that adolescents who ate at least 12.9 grams of nuts per
day – this is the equivalent of about 1 ounce of nuts 3 times per week – had a dramatically
lower odds for metabolic syndrome compared to adolescents who ate less than that amount.
The odds for nut-consumers was only about 43% of the odds for non-consumers. This
remained true after controlling for age, gender, race, income, and dietary factors including
sugar, fruit, and vegetable intake.
• Our second major finding was that average nut intake is very low among US adolescents –
only about 5 grams per day – and more than 75% of US adolescents eat no nuts at all on a
typical day.
• Dr. Kim: First, that a modest amount of daily nut consumption among adolescents is
associated with a much reduced odds for metabolic syndrome. This corroborates in
adolescents what has been observed in many studies of adults. Our study was cross-
sectional, however, so causality cannot be determined. And the second take away point is
that, in spite of what we are learning about the health benefits of nut consumption, the vast
majority of US adolescents eat no nuts at all on a typical day.

Dr. Roy Kim, MD
this study?
• Dr. Kim: Further prospective research is needed to test whether prescribing nuts to
adolescents will improve their cardiovascular risk profile.
• Citation:
• ENDO abstract discussing:
• Nut Intake and its Relationship to Metabolic Syndrome in Adolescents
• Authors: Roy J. Kim, MD, MPH, and David Leonard, PhD
• University of Texas Southwestern Medical Center, Department of Pediatrics,
Division of Endocrinology, and Children’s Health, Dallas,
• MedicalResearch.com Interview with: Dr. Roy Kim, MD, Depts. Endocrinology and
Pediatrics, UT Southwestern Medical Center (2015). Nuts May Lower Odds Of Metabolic
Syndrome In Adolescents

Genetically Modified Soybean Oil Plenish Only Slightly Healthier Than Regular Soybean Oil
Frances M. Sladek, Ph.D. Professor of Cell Biology and Toxicologist
Associate Director, UCR Stem Cell Center
Department of Cell Biology and Neuroscience University of California
Riverside, CA 92521-0314
Dr. Sladek: In 2011 Blasbalg et al reported in the American Journal of Clinical Nutrition that
the consumption of soybean oil was the component of the American diet that had changed
the most since the early 1900s. It had in fact increased 1000-fold. Soybean oil is currently not
only the main type of vegetable oil used in the U.S. but soybean meal is a major component
of the diet of the animals such as cows and pigs, resulting in changes in the fatty acid
composition of animal fat. Soybean oil is also increasingly being used worldwide: 40 million
tons were produced in 2007 alone.
• In our previous study we found that a high fat diet containing comparable amounts of
soybean oil to what Americans are currently consuming caused mice to become obese,
diabetic and insulin resistant and to have large lipid droplets and hepatocyte ballooning in
their livers.
• Others had found similar results and proposed that linoleic acid (an omega 6 polyunsaturated
fat) that makes up >55% of the oil was responsible for the negative metabolic effects.

• DuPont recently generated a genetically modified soybean oil that had reduced levels of
linoleic acid and hence less of a tendency to generate trans fats. This oil (called Plenish) came
onto the market for the first time in 2014. The fatty acid composition of Plenish is similar to
that of olive oil (low linoleic acid and high oleic acid), which is a major component of the
healthy Mediterranean diet. The implication, therefore, is that Plenish is healthier than
conventional soybean oil but that has not been formally proven.
• In the current study, we found that while a high fat diet containing Plenish also induced
obesity, glucose intolerance and fatty liver, it did not induce insulin resistance as did the
conventional soybean oil. It also induced somewhat less fat accumulation.
• Finally, we compared the diet enriched in soybean oil to an isocaloric diet that contained the
same amount of total fat (40%kcal, Americans consume 34-37% fat) but with 90% of the fat
from coconut oil. Those animals gained very little weight (13% versus 38% with the
conventional soybean oil and 30% with the Plenish) and were not diabetic or insulin resistant.
Their livers also had less fat than either of the two soybean oil diets and showed no signs of
hepatocyte ballooning. Coconut oil has essentially no linoleic acid or other PUFAs.
• Our results, assuming humans respond in the same way as mice, suggest that people should
avoid the consumption of too much soybean oil, either conventional or Plenish. They also
show that coconut oil, which is made up of saturated fats (primarily medium chain
triglycerides), is much healthier for you than soybean oil. Coconut oil has been noted
previously for its beneficial health effects.

• Dr. Sladek: The clinical implications are that the ubiquitous presence of soybean oil in the
American diet could be contributing to the obesity epidemic. The introduction of the GM
soybean oil Plenish with low linoleic acid into the American food chain could potentially
reverse that trend.
• Soybean oil is in most vegetable oils and processed foods and is widely used in restaurants,
making it difficult to avoid. The best approach is to cook with olive oil at home and eat as few
processed foods as possible.
• We should also note that the effects we observed are from soybean oil; there is no indication
that soybean protein (i.e., tofu) or soy milk induce the same effects.

• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Sladek: We need more research on the health effects of soybean oil, both in mouse models that
have the advantage of being able to rigorously control for all the various parameters, as well as in
humans. Since soybean oil is so ubiquitous in the U.S. and is being increasingly used worldwide at
levels of consumption never seen in the past that it is vital that we know what it does to our
metabolism.
• We need to determine what component(s) other than linoleic acid is driving the negative metabolic
effects of soybean oil. With that knowledge it might be possible to genetically modify soybeans
further so that they are truly beneficial to our health.
• Finally, we need to determine what tissues other than liver are primarily affected by soybean oil –
does it act on adipose tissue? the gut? the pancreas? – as well as the molecular mechanism by
which it targets those organs.
• Other components of the American diet such as saturated fats from animal products and fructose
in high fructose corn syrup have received a lot of scientific as well as media attention. And yet
soybean oil, which is an equally important part of our diet and arguably more difficult to avoid, is
highly understudied.
• Citation:
• ENDO meeting abstract discussing:
Genetically Modified Soybean Oil Only Slightly Healthier than Regular Soybean Oil
MedicalResearch.com Interview with: Frances M. Sladek, Ph.D. (2015). Genetically Modified
Soybean Oil Plenish Only Slightly Healthier Than Regular Soybean Oil

Early Onset, Frequent Hot Flashes Linked To Increased Cardiovascular Disease Risk
Dr. Rebecca Clark Thurston Ph.D
Associate Professor of Psychiatry, Epidemiology, Psychology, and Clinical and Translational Science
University of Pittsburgh
• MedicalResearch: What is the background for these studies? What are the main findings?
• Dr. Clark Thurston: The understanding of women’s cardiovascular disease and the role that
reproductive factors play in women’s cardiovascular health is evolving. There are some
studies showing links between menopausal hot flashes and cardiovascular disease risk in
women. These studies help further refine this understanding. We showed in two separate
studies that women who have hot flashes, particularly frequent hot flashes early in midlife,
have poorer vascular health on certain indices.

• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Clark Thurston: Women who experience hot flashes at relatively young ages – in their 40’s
– particularly if the hot flashes are frequent, should be sure they are getting their regular
health check ups. Stay on top of their blood pressure, lipids, glucose, and weight. If they are
smoking, stop, if they are overweight, now is the time to try to lose. Start exercising. Midlife
is really the time for women to set up good heart health behaviors that will serve them well
as they age. Women should remember that cardiovascular disease is the leading cause of
death among women.

• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Clark Thurston: We need to look at other aspects of cardiovascular health in relation to
hot flashes. We need to really refine that age at which hot flashes are most predictive of
adverse vascular health. We need to understand how these data might inform our
approaches to treating hot flashes among younger women, and may encourage us as
providers to use methods that have the lowest cardiovascular risk associated with them.
• Citation:
• upcoming ACC abstracts:
• Early-Onset Menopausal Vasomotor Symptoms Are Associated with Endothelial Dysfunction:
The National Heart Lung and Blood Institute-Sponsored Women’s Ischemia Syndrome
Evaluation (WISE) Study and
• Physiologically-Assessed Hot Flashes Are Associated with Poorer Endothelial Function Among
Early Midlife Women
MedicalResearch.com Interview with:Dr. Rebecca Clark Thurston Ph.D (2015). Early Onset,
Frequent Hot Flashes Linked To Increased Cardiovascular Disease Risk

Sense of Purpose in Life Reduces Cardiovascular Risk
Randy Cohen, MD, MS, FACC
Division of Cardiology Mt. Sinai St. Luke’s Hospital
New York, NY
• MedicalResearch: What is the background for this study?
• Dr. Cohen: Psychosocial conditions such as depression, anxiety, chronic stress and social
isolation have strong associations with heart disease and mortality. Recently, however,
attention has focused on positive emotions, psychological health and their collective impact
on overall health and well-being. Purpose in life is considered a basic psychological need,
and has been defined as a sense of meaning and direction in one’s life which gives the feeling
that life is worth living. We performed a meta-analysis of prospective studies evaluating the
relationship between having a sense of purpose in life, mortality and cardiovascular disease.
• MedicalResearch: What are the main findings?
• Dr. Cohen: We identified 10 prospective studies involving over 137,000 subjects and found
that possessing a sense of purpose in life was associated with a 23% reduced risk for all-cause
mortality and a 19% reduced risk for cardiovascular disease events.

Sense of Purpose in Life Reduces Cardiovascular Risk
Randy Cohen, MD, MS, FACC
Division of Cardiology Mt. Sinai St. Luke’s Hospital
New York, NY
this study?
• Dr. Cohen: Future research should focus on the following:
• Develop practical screening tools for clinicians to assess for psychosocial factors (positive and
negative) known to be associated with poor health outcomes.
• Develop and test practical interventions for individuals identified as having low purpose.
• Citation:
• presented on March 6 at the American Heart Association’s EPI/Lifestyle 2015 Scientific
Sessions in Baltimore.
• Sense of purpose may lower risk of death, heart attack, strok

Genetic Study Confirms Most Pediatric Melanoma Linked To Sun Exposure
Alberto Pappo, M.D.
Member, Oncology; Director, Solid Tumor Division
St. Jude Children’s Research Hospital
• Dr. Pappo: Researchers have identified three distinct subtypes of childhood and adolescent tumors
of pigment-producing skin cells called melanocytes. The subtypes have different genetic alterations
and often different outcomes for patients. The findings should aid efforts to improve diagnosis and
treatment of melanoma, which is the most common skin cancer in children and adolescents.
• The study provides the most comprehensive analysis yet of the genetic alteration underlying
pediatric melanoma, including the first genetic evidence that sun damage causes melanoma in
children and adolescents as well as adults. Researchers used whole genome sequencing and other
techniques to study the normal and cancer genomes of 23 young patients with a variety of
melanocytic tumors, including conventional melanoma. Patients ranged in age from 9 months to 19
years old.
• The melanoma subtypes in this study included conventional melanoma, which scientists showed
was the same disease in children, adolescents and adults. More than 90 percent of pediatric
conventional melanoma had DNA changes linked to sun damage.
• Dr. Pappo: The findings reinforce the importance of sun protection beginning early in life. The
results also underscore the need to make it easier for younger patients with conventional
melanoma to access promising therapeutic agents being tried in adults. Clinicians and patients
should take away that conventional melanoma in adolescents is very similar to adult melanoma and
that UV plays a role in the pathogenesis of this disease.

Genetic Study Confirms Most Pediatric Melanoma Linked To Sun Exposure
Alberto Pappo, M.D.
Member, Oncology; Director, Solid Tumor Division
St. Jude Children’s Research Hospital
this study?
• Dr. Pappo: We would like to expand our observations by creating a registry.
• Citation:
• The Genomic Landscape of Childhood and Adolescent Melanoma
• Charles Lu1,11, Jinghui Zhang2,11, Panduka Nagahawatte2, John Easton2, Seungjae Lee3,
Zhifa Liu4, Li Ding1,5,6,7, Matthew A Wyczalkowski1, Marcus Valentine8, Fariba Navid9,
Heather Mulder2, Ruth G Tatevossian3, James Dalton3, James Davenport3, Zhirong Yin3,
Michael Edmonson2, Michael Rusch2, Gang Wu2, Yongjin Li2, Matthew Parker2, Erin Hedlund2,
Sheila Shurtleff3, Susana Raimondi3, Vadodaria Bhavin2, Yergeau Donald2, Elaine R Mardis5,6,7,
Richard K Wilson5,6,7, William E Evans10, David W Ellison3, Stanley Pounds4, Michael Dyer2,
James R Downing3, Alberto Pappo9 and Armita Bahrami3 for the St Jude Children’s Research
Hospital–Washington University Pediatric Cancer Genome Project
• Journal of Investigative Dermatology (2015) 135, 816–823; doi:10.1038/jid.2014.425;
published online 30 October 2014

More Medical Advice May Help Patients Reduce Salt Intake
Dr. Sandra L. Jackson, Ph.D., M.P.H
Epidemic intelligence service fellow
Centers for Disease Control and Prevention, Chamblee, GA
Dr. Jackson: With more than 90 percent of U.S. adults exceeding recommended sodium
intake levels, healthcare providers can play a key role in counseling patients on the
importance of limiting salt in the diet.
• To assess the impact of medical advice on an individual’s efforts to reduce sodium intake, CDC
researchers examined self-reported telephone survey information from nearly 174,000 U.S.
adults. Overall, more than half of the respondents reported watching or reducing their
sodium intake in 2013 – but less than one quarter (23 percent) said they received advice
from a doctor or healthcare professional about sodium reduction. Of those that received the
medical advice, 82 percent reported taking action to limit their sodium intake. In comparison,
only 44 percent of respondents who reported not receiving medical advice said they took
steps to reduce sodium.
• The substantial proportion of patients who are not receiving medical advice (77%), according
to these findings, reveals a missed opportunity to reduce sodium intake, particularly among
groups that have a higher risk of developing cardiovascular disease. This includes African
Americans, and those with high blood pressure, diabetes or chronic kidney disease.

• Dr. Jackson: This study is meaningful because it is one of the only ones to examine how
sodium-related medical guidance relates to all patients, not just those with hypertension.
With only one-quarter of respondents in this study reporting that they received medical
advice about sodium, there is room for improvement.
• Heart disease, stroke and other cardiovascular diseases kill nearly 800,000 Americans each
year and cost more than $320 billion dollars a year in health care and lost productivity. CDC
supports reducing sodium as an effective way to lower blood pressure and improve heart
health and reduce risk for stroke nationwide. We encourage doctors to discuss the
importance of limiting sodium with all patients to prevent and to help reduce blood pressure.

this study?
• Dr. Jackson: Further research could identify optimal strategies for reducing sodium in the
diet. Also, while this study examined health professional advice related to sodium intake,
there are other avenues of public health messaging and education. Additional research could
examine the effectiveness of sodium reduction messaging delivered through other channels.
• Citation:
• Research presented at the American Heart Association EPI/Lifestyle 2015 meeting.
Medical advice to limit salt intake may help adults reduce sodium

Can Phthalates Alter Sex Development During Pregnancy?
Dr. Jennifer Adibi, MPH ScD University of Pittsburgh, Public Health Assistant Professor, Epidemiology
Assistant Professor, Department of Obstetrics/Gynecology and Reproductive Sciences
Affiliate, Dept. of ObGYN and Reproductive Sciences University of California, San Francisco
Medical Research: What is the background for this study?
Dr. Adibi: Prenatal exposure to phthalates in rodents can cause defects in male sexual
development including a shorter distance between the anus and the genitalia (anogenital
distance or AGD). Human studies have shown a correlation between higher prenatal phthalate
urinary concentrations in the mother and shorter AGD in males. AGD in males is related to
fertility and reproductive health over the lifetime. In females, AGD was associated with numbers
of ovarian follicles. The role of the placenta has not been considered in these studies.
A placental hormone called human chorionic gonadotropin (hCG) is essential for normal male
development. Our previous research has shown that hCG expression by human placental cells is
disrupted by phthalate concentrations equal to what we measured in maternal urine. The
placenta secretes molecules early in pregnancy that might provide an opportunity to detect these
effects in humans.

• Medical Research: What are the main findings?
• Dr. Adibi: In 350 pregnancies, we measured a significant association of maternal urinary
concentrations of mono-n-butyl phthalate (MnBP) and monobenzyl phthalate (MBzP) with
hCG in maternal blood in the first trimester. Higher phthalate concentrations were
associated with higher hCG if the mother was carrying a female fetus, and lower
concentrations if she was carrying a male fetus. In a high/low MnBP comparison, hCG was
15-fold higher in the higher exposed female fetuses. We also observed a relationship
between maternal levels of hCG in the first trimester and anogenital distance
in the newborns. The correlation was positive in female newborns, and inverse in male
newborns. Similar to the parent study, we observed associations of higher first trimester
MnBP and mono-2-ethyl hexyl phthalate (MEHP) with lower male anogenital distance. If we
combined these findings into a mediation analysis, we estimated that approximately 20-30%
of the phthalate-induced effect on anogenital distance was due to the phthalate disruption of
hCG.

• Dr. Adibi: With more studies and a better understanding of these relationships and the role
of the placenta in endocrine disruption, we may have the possibility to detect these types of
hormonal balances earlier in pregnancy and intervene within an early time frame to protect
the long-term health of the future child. A pregnant woman should do her best to reduce her
exposures; however, it is difficult to do this as intervention studies have shown. Meaningful
changes in this exposure can only happen at the societal level with changes in regulation,
industry practices, and innovation in consumer product design

this study?
• Dr. Adibi: We are going to repeat this study with serial maternal blood and urine samples
before 14 weeks in pregnancy to better understand these relationships at the population
level. First trimester hCG is widely available as it is measured as part of prenatal screening
for Down’s Syndrome and other defects. These results support more studies to understand
the role of placental hCG in fetal origins of health and disease, and as a target of endocrine
disruption.
• Citation:
• ENDO 15 abstract:
Phthalates potentially alter levels of a pregnancy hormone that influences sex development

Depression Remains Important Risk Factor For Cardiovascular Disease
Heidi May, Ph.D., M.S.P.H.
Cardiovascular Epidemiologist
Intermountain Medical Center Heart Institute Salt Lake City
Medical Research: What is the background for this study? What are the main findings?
Dr. Heidi May: Cardiovascular disease remains the leading cause of morbidity and mortality
worldwide. Statin therapy is known to reduce the risk of cardiovascular disease incidence through
the reduction of blood cholesterol levels and through its pleiotropic cardioprotective properties.
Depression is a risk factor for cardiovascular disease. It has been recommended that
antidepressant medications should be considered first-line treatment for depression of any
severity. We hypothesized that taking both statins and antidepressants would reduce
cardiovascular risk more than either medication alone. However, we did not find this. Instead we
found that the effectiveness of antidepressants and statin therapy to reduce death and incident
cardiovascular disease at 3 years varied by the severity of depressive symptoms. Among those
with none to mild depressive symptoms, statin use, with or without antidepressant therapy, was
associated with a decrease in risk, but among those with moderate to severe depression,
antidepressant use was associated with a decrease in risk. The combination of antidepressant
and statin use did not result in a greater risk reduction in either depressive symptom category.

• Dr. Heidi May: This study supports the importance of depression as a risk factor for
cardiovascular disease and the importance of its treatment. Assessment of depression should
be made by clinicians like any other cardiovascular risk factor (high blood pressure, high
cholesterol levels).

this study?
• Dr. Heidi May: I would like to see this study replicated in other populations and among
different classes of antidepressants. It would also be interesting to evaluate these results
among different subgroups of patients (women vs. men, older vs. younger, different levels of
cholesterol, diabetics).
• Citation:
• The Association of Antidepressant and Statin Use to Future Death and Incident
Cardiovascular Disease Varies by Depression Severity,” will be presented on March 15 at 9:30
a.m. PT/12:30 p.m. ET/4:30 p.m. at the ACC15 Conference

Unvaccinated Children Have Higher Risk Of Developing Shingles
Su-Ying Wen, MD Chief of Department of Dermatology,
Taipei City Hospital, Renai Branch, Taipei City, Taiwan
Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei City, Taiwan
Dr. Su-Ying Wen: Though herpes zoster is seen as a disease of the elderly, it can affect
individuals in any age group including children. There are limited population-based data
regarding pediatric herpes zoster.
• We reported a higher incidence rate of pediatric herpes zoster than in previous studies. The
higher incidence observed in this population-based study might be because it was measured
in a cohort of children who were all infected with varicella rather than as other reports
including individuals free of varicella infection in the denominator. Children younger than 2
years at the diagnosis of varicella had a significantly higher risk and shorter duration of
developing herpes zoster.
• Dr. Su-Ying Wen: The children with a history of varicella had a significantly higher risk of
developing pediatric herpes zoster than those who received varicella vaccine. Children
contracting varicella before the age of 2 years had at least 2-fold increased the risk of
developing pediatric herpes zoster than those contracting varicella after the age of 2 years.

Unvaccinated Children Have Higher Risk Of Developing Shingles
Su-Ying Wen, MD Chief of Department of Dermatology,
Taipei City Hospital, Renai Branch, Taipei City, Taiwan
Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei City, Taiwan
this study
• Dr. Su-Ying Wen: The results of the current study may serve as baseline data for the early
effects of varicella vaccinations on pediatric herpes zoster. Long term studies are required to
monitor the impact of a varicella vaccination program on pediatric herpes zoster.
• Citation:
• Epidemiology of Pediatric Herpes Zoster After Varicella Infection: A Population-Based Study
• Su-Ying Wen and Wen-Liang Liu
• Pediatrics peds.2013-4037; published ahead of print February 23, 2015,
doi:10.1542/peds.2013-4037

Skilled Team Work Required For Endovascular Treatment of Ischemic Stroke
Michael D Hill, MD MSc FRCPC Calgary Stroke Program
Professor, Dept Clinical Neurosciences Hotchkiss Brain Institute
University of Calgary, Cumming School of Medicine Foothills Hospital, Calgary, Canada
Dr. Hill: Major ischemic stroke with blocked proximal arteries results in 60-80% death and
disability. Recent studies of endovascular treatment were neutral. Evolution of technology has
resulted in advances in the devices. Key features of past trials of endovascular therapy were,
underdeveloped imaging paradigms for patient selection, slow treatment times and poor
reperfusion rates.

• Dr. Hill: Simply, endovascular therapy for major ischemic stroke over and above best medical
care (ie. IV tPA) is effective . It reduces disability and saves lives. The NNT is very low 4,
making it one of the largest proven effect sizes in all of medicine. BUT, it applies only under
selected conditions.
• First, you need a team. This means a stroke team, from pre-hospital, ED physicians and
nurses, neuroradiology support, stroke neurology, stroke intervention and the stroke unit
and rehabilitative support. Without the team this therapy does not work. All patients who
are eligible should rapidly receive intravenous tPA.
• Second, you must image the patients to select those who will benefit from therapy. You must
demonstrate a small core, a blocked intracranial large artery and evidence of good collateral
flow. You must do this very fast.
• Third, you must act very quickly . This is where the team comes in. Imaging (CT) to groin
puncture time should be less than 60 minutes and imaging (CT) to reperfusion time should be
less than 90 minutes.
• And finally, you should use the available novel technology to get the artery completely open.
• I must emphasize that it is the triad of imaging, speed and reperfusion, performed by a team
that will work. This is what we have shown in ESCAPE. It is and was a huge team effort.

• Medical Research: What recommendations do you have for future research as a result of this study?
• Dr. Hill: Key issues to resolve are:
• (1) What is the best imaging paradigm to select patients?
• (2) 45% of patients still did poorly. How do we improve the therapy for them?
• (3) How do we improve the procedure to get the reperfusion rates from 80% to 99%.
• (4) How do implement this therapy? What is the best way to triage stroke patients to the right centre to
the right team in the right timeframe to get this therapy?
• Citation:
• Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke
• Mayank Goyal, M.D., Andrew M. Demchuk, M.D., Bijoy K. Menon, M.D., Muneer Eesa, M.D., Jeremy L.
Rempel, M.D., John Thornton, M.D., Daniel Roy, M.D., Tudor G. Jovin, M.D., Robert A. Willinsky, M.D.,
Biggya L. Sapkota, M.B., B.S., Dar Dowlatshahi, M.D., Ph.D., Donald F. Frei, M.D., Noreen R. Kamal, M.D.,
Walter J. Montanera, M.D., Alexandre Y. Poppe, M.D., C.M., Karla J. Ryckborst, R.N., Frank L. Silver, M.D.,
Ashfaq Shuaib, M.D., Donatella Tampieri, M.D., David Williams, M.B., Ph.D., Oh Young Bang, M.D., Ph.D.,
Blaise W. Baxter, M.D., Paul A. Burns, M.B., Ch.B., M.D., Hana Choe, M.D., Ji-Hoe Heo, M.D., Ph.D.,
Christine A. Holmstedt, D.O., Brian Jankowitz, M.D., Michael Kelly, M.D., Ph.D., Guillermo Linares, M.D.,
Jennifer L. Mandzia, M.D., Ph.D., Jai Shankar, M.D., Sung-Il Sohn, M.D., Richard H. Swartz, Ph.D., Philip A.
Barber, M.B., Ch.B., M.D., Shelagh B. Coutts, M.B., Ch.B., M.D., Eric E. Smith, M.D., M.P.H., William F.
Morrish, M.D., Alain Weill, M.D., Suresh Subramaniam, M.D., Alim P. Mitha, M.D., John H. Wong, M.D.,
Mark W. Lowerison, M.Sc., Tolulope T. Sajobi, Ph.D., and Michael D. Hill, M.D. for the ESCAPE Trial
Investigators
• N Engl J Med 2015; 372:1019-1030 March 12, 2015

Do Emulsifiers in Food Additives Play A Role In Inflammatory Bowel Diseases?
Benoit Chassaing, Ph.D.
Post-Doctoral Fellow Dr. Gewirtz’s lab. Institute for Biomedical Sciences
Center for Inflammation, Immunity, & Infection Georgia State University Atlanta GA 30303
Dr. Chassaing: A key feature of inflammatory bowel diseases and metabolic syndrome is
alteration of the gut microbiota in a manner that promotes inflammation. Importantly,
incidence of IBD and metabolic syndrome has been markedly increasing since about the mid-
20th century, and this dramatic increase has occurred amidst constant human genetics,
suggesting a pivotal role for an environmental factor. We considered that any modern
additions to the food supply might play an important role, and addition of emulsifiers to food
seems to fit the time frame of increased incidence in these diseases. We found that
emulsifiers, which are added to most processed foods to aid texture and extend shelf life, can
alter the gut microbiota composition and localization to induce intestinal inflammation that
promotes development of inflammatory bowel disease and metabolic syndrome.
• Dr. Chassaing: More work is definitively required to be able to translate these important
findings to humans.
• We personally have changed our habits, trying to avoid processed food, generally loaded with
emulsifiers. Food products can be found without emulsifiers, with of course a shelf life much
shorten compare to emulsifiers containing foods. However, in order to more strictly regulate
such emulsifiers, human trials will be needed in order to confirm that similar deleterious
affects are observed on human as well.

Do Emulsifiers in Food Additives Play A Role In Inflammatory Bowel Diseases?
Benoit Chassaing, Ph.D.
Post-Doctoral Fellow Dr. Gewirtz’s lab. Institute for Biomedical Sciences
Center for Inflammation, Immunity, & Infection Georgia State University Atlanta GA 30303
this study?
• Dr. Chassaing: We both think that more research is needed before altering regulation of such
additives. Almost all food additives are tested on animals that are relatively resistant to most
disease, and those test are analyzing acute toxicity or cancer promotion. However, in order to
more strictly regulate such emulsifiers, human trials will be needed in order to confirm that
similar deleterious affects are observed on human as well. We are working on setting up such
trial in a near future with our collaborators. Nonetheless, and as stated above, we personally
already have changed our habits.
• Citation:
• Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic
syndrome
• Benoit Chassaing,Omry Koren,Julia K. Goodrich,Angela C. Poole,Shanthi Srinivasan,Ruth E.
Ley & Andrew T. Gewirtz
• Nature 519, 92–96 (05 March 2015) doi:10.1038/nature14232

Estrogen Therapy In Young Women May Not Increase Breast Cancer Risk
Medicalresearch.com Interview with:
Dr. Clarice R. Weinberg Ph.D
Biostatistics and Computational Biology Branch
National Institute of Environmental Health Sciences Research Triangle Park, NC 27709
• Dr. Weinberg: Hormone therapy (HT) was commonly prescribed in the U.S. late in the 20th
century to help women through the challenges of menopause. Several decades ago, therapy
with estrogen alone was shown to cause endometrial cancer, and the combined use of both
estrogen and progesterone replaced treatment with estrogen alone. But research published
around 2002 had far reaching effects on gynecologic practice. Both the randomized trial
component of the US Women’s Health Initiative and the observational European Million
Women’s Study reported that postmenopausal women who were older than 50 and were
taking the combination HT had an increased risk of breast cancer. Physicians and patients
responded quickly, and Hormone therapy use plummeted.
• However, it remained unclear whether there were risks of Hormone therapy use in women
under age 50. Some factors, for example obesity, have opposite effects on the risk of breast
cancer in pre- and post-menopausal women, so one cannot assume risk findings from older
women necessarily apply to younger women. We carried out a sibling-based study of 1,419
women with breast cancer diagnosed under the age of 50
(http://sisterstudy.niehs.nih.gov/English/2sis.htm). Each case had a sister (also studied) who
had never been diagnosed with breast cancer, who could serve as her control. The study was
funded by Susan G. Komen for the Cure, and the National Institutes of Health.

• Dr. Weinberg: We estimated that women who had only taken estrogen (without
progesterone) had a 42 percent decrease in their risk of young-onset breast cancer,
compared to women of similar age who had never taken Hormone therapy. Women who had
taken the combination estrogen plus progesterone showed no increase in risk, but there
were few with this exposure and we cannot rule out increased risk for the combination
therapy. Interestingly, participants in the Women’s Health Initiative who were randomized to
estrogen alone had reduced risk of fractures and reduced risk of breast cancer. However, that
study had to be discontinued because those women showed increased risk of stroke.
• Dr. Weinberg: In women under age 50, estrogen therapy does not appear to increase the risk
of breast cancer. We did not study whether use of estrogen before 50 might affect risk at
later ages.

this study?
• Dr. Weinberg: Our data suggest that estrogen use before age 50 is less harmful than
commonly assumed, and might actually confer some protection against breast cancer.
However, these findings require replication through additional research. Since a randomized
trial would probably not be feasible, we would like to see an observational study that
carefully ascertains the indications for use when a young woman reports taking estrogen
alone. Such data will be helpful in ruling out the possibility that it is the underlying indications
and not the estrogen that confers protection against breast cancer. Prospective follow up
beyond age 50 would also be valuable.
• Citation:
• Hormone Therapy and Young-Onset Breast Cancer
• Katie M. O’Brien, Chunyuan Fei, Dale P. Sandler, Hazel B. Nichols, Lisa A. DeRoo, and Clarice R.
Weinberg
Am. J. Epidemiol. first published online February 18, 2015 doi:10.1093/aje/kwu347

Tooth Enamel Defects May Reflect Perinatal Exposure to Bisphenol A
Sylvie Babajko, PhD
Centre de Recherche des Cordelier Inserm UMR_S 1138
Laboratoire de Physiopathologie Orale Moléculaire 75006 Paris cedex 06
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Babajko: The environment has become increasingly contaminated by various pollutants.
This has led to an increase in the incidence and gravity of known pathologies and/or the
emergence of new pathologies. In 2001, a distinct enamel pathology called molar incisor
hypomineralization (MIH) was described. It is diagnosed by white to brown creamy lesions
affecting permanent first molars and frequently permanent incisors too. These teeth are
sensitive and susceptible to caries. MIH prevalence turns around 15-18 % of 6 to 9 years-old
children in studied populations all over the world. To date, MIH etiology remains unclear.
However, given that MIH affects those teeth that are undergoing mineralization around the
time of birth, MIH is indicative of some adverse event(s) occurring during early childhood
that impact on enamel development. Interestingly, susceptibility to BPA in human is the
highest during the same period of time.
• Our experimental data (1, 2) showed that BPA may be a causal agent of MIH and that BPA
irreversibly impacts amelogenesis via steroid hormone pathway.

Sylvie Babajko, PhD
• Dr. Babajko: We propose that affected teeth could be used as early marker of exposure to
EDCs acting as BPA.
• The EDCs (especially BPA) are suspected of being involved in a variety of pathologies such as
obesity, infertility, behavioral disorders or even hormone-dependent cancers. Therefore,
clinicians should examine the teeth of their patients affected by one of these pathologies.
And in particular, they should take into account MIH (if any) as an easy marker of exposure to
these agents.
• Similarly, parents of children affected by MIH should be particularly vigilant to limit exposure
to EDCs (eg avoiding industrial food packed in plastic containers that is probably the main
source of contamination). Patients should request information to their dentist on the
materials used for restoration or to protect from caries to be sure they’re BPA free.

Sylvie Babajko, PhD
this study?
• Dr. Babajko: Epidemiological data would help to identify the potential correlation between
MIH and other endocrine pathologies (to be precisely characterized). Such data are expected
to argue the use of affected teeth as easy (and cheap) marker of exposure to EDCs.
• (1): Jedeon et al., Am J Pathol, 2013, 183(1):108-18
• (2): Jedeon et al., Endocrinology, 2014, 155(9):3365-75
• ENDO15 March 2015
• Enamel Defects Reflect Perinatal Exposure to Bisphenol A
• Sylvie Babajko, Katia Jedeon, et al.
• -Research Centre of Cordeliers, INSERM UMRS 1138, Laboratory of Molecular Oral
Pathophysiology, Paris, France
• -Paris-Diderot University, UFR Odontology, Paris, France

Why Is It So Hard To Reach Our Behavior Goals?
Margaret C. Campbell, Phd | Professor | Marketing
Chair, Doctoral Curriculum Program Committee437 Leeds School of Business
University of Colorado at BoulderBoulder, CO 80309-0419
Dr. Campbell: People try to maintain healthy body weights, attain academic and career success,
save money for a car, a house, or retirement, and achieve a host of other goals that require
repeated, goal-consistent behaviors. Unfortunately, consumers’ efforts often fall short. For
example, 68% of Americans are overweight (Weight Control Information Network 2010), 46% who
begin college do not graduate within six years (Associated Press 2006), and although 93% say that
saving for retirement is important, only about 60% are actually saving (TIAA-CREF 2010) and
approximately 50% have accumulated less than $25,000 (Helman, VanDehrei and Copeland 2007).
Understanding goal pursuit and consumers’ choices to continue effort toward a goal that requires
repeated goal-consistent behaviors is thus important. People need to be able to make progress on
important goals that substantially impact their quality of life.
• Monitoring the influence of behavior on distance from a focal goal has been identified as important
for successful goal pursuit – such as weight loss. In seven experiments, we find that people tend to
have a “progress bias” such that they perceive that goal-consistent behaviors (such as avoiding
eating a piece of cake) help progress more than equivalent-sized goal-inconsistent behaviors (such
as eating a piece of cake) hurt progress. An experiment on exercise and eating shows that the
progress bias can lead to poor understanding of progress and thus, premature release of the goal.
In this study, the progress bias resulted in people with a goal of expending more calories than they
consumed ended up consuming more than they expended.

• Dr. Campbell: This research is meaningful because it provides evidence of a persistent
tendency for people to mis-estimate the effects of their consistent versus inconsistent
behaviors. We think that understanding this bias can help people to avoid it. Clinicians and
patients can focus on more careful monitoring of patients’ behaviors so that they have better
insight into their actual goal progress. For example, knowing that there is a tendency to think
that “good” behaviors are great and “bad” behaviors are not so bad, patients can be
encouraged to carefully record both types of behaviors to assess their actual progress.

this study?
• Dr. Campbell: Further research could identify interventions to help patients better
understand the effects of their behaviors on their goal progress and to study the extent to
which this can help with goal achievement. For example, research on more careful
consideration of both “energy in” and “energy out” on weight goals would be useful.
• Citation:
• The Progress Bias in Goal Pursuit: When One Step Forward Seems Larger than One Step Back
• Margaret C. Campbell
University of Colorado at Boulder
Caleb Warren
Texas A&M University – Department of Marketing
January 30, 2015
Journal of Consumer Research, Vol. 41, February 2015
Mays Business School Research Paper No. 2015-15

Gene Signature May Predict Risk of Metastases and Death From Melanoma
Pedram Gerami MD
Associate Professor of Dermatology and Pathology
Northwestern University
• Dr. Gerami: The outcomes for patients with cutaneous melanoma are highly variable and
there are limitations to the conventional staging system for melanoma. For example while
the status of the sentinel lymph node biopsy is considered the strongest prognosticator,
approximately 2/3 of cutaneous melanoma patients that ultimately die from their melanoma
will have a negative sentinel lymph node biopsy result. In this study we showed that using a
technique known as mRNA expression profiling to determine which genes are highly active
and which are not that a molecular prognostic assay with accuracy could be developed. This
assay can accurately classify patients based on their gene signature as having a high or low
risk for metastasis and death from their melanoma. In an independent validation cohort,
patients with a class I or low risk signature had a 5 year disease free survival rate of 97%
while those with a class II or high risk signature had a 5 year disease free survival rate of only
31%.
• Dr. Gerami: This assay maybe used to better predict prognosis and to better guide follow up
and management. For example one may choose to have a patient with a class II signature to
have more frequent imaging studies and closer clinical follow up.

Gene Signature May Predict Risk of Metastases and Death From Melanoma
Pedram Gerami MD
Associate Professor of Dermatology and Pathology
Northwestern University
this study?
• Dr. Gerami: In the future it would be beneficial to determine whether patients with no
evidence of active disease but with a class II signature would have any survival benefit from
adjuvant therapy.
• Citation:
• Gene expression profiling for molecular staging of cutaneous melanoma in patients
undergoing sentinel lymph node biopsy
• Gerami, Pedram et al.
• Journal of the American Academy of Dermatology
• DOI: http://dx.doi.org/10.1016/j.jaad.2015.01.009
• Accepted: January 5, 2015; Published Online: March 04, 2015

Curvy Bottoms Linked To Pregnancy Advantage
Dr. David M.G. Lewis, PhD
Assistant Professor Department of Psychology Bilkent Üniversitesi Ankara, Turkey Research Affiliate,
Individual Differences and Evolutionary Psychology Area Department of Psychology The University of Texas at Austin
• Dr. Lewis: My motivations to conduct this study were a combination of several things. Men would
often mention to me the features that they found attractive in women. They would often mention
the butt, but not the *size* of the butt…it was something else, but they couldn’t seem to put their
finger on exactly what…
• I then began reading more deeply into the different muscular, ligamentous, skeletal, etc. structures
that could influence the appearance of the buttocks. I moved beyond just buttock tissue and
buttock size. What I began to discover is that while the size of the buttocks does indeed influence
the buttocks’ appearance, so too does other morphology that is not part of the buttocks
themselves. These readings indicated that certain spinal structures can help women shift their
center of mass back over the hips during pregnancy and reduce hip torque by roughly 700%. To the
extent that women who possess these spinal structures would thereby be better able to carry a
pregnancy (or multiple pregnancies) to term without suffering spinal injuries, selection would have
favored the evolution of psychological mechanisms in men to prefer women exhibiting cues to
these spinal structures. Men could not directly observed women’s vertebrae, but lumbar curvature
is an externally visible cue to the relevant spinal structures.
• At this point, we had a hypothesis that was both anchored in evolutionary theory and grounded in
medical orthopedic literature. It was time we tested our idea that men possess a previously
undiscovered, evolved preference for a beneficial intermediate angles of lumbar curvature in
women.

• Dr. Lewis: The key findings are that men possess a previously undiscovered preference in
women — one that is rooted in spinal structures that influence a woman’s lumbar curvature
but also the protrusion of her buttocks. We know that this preference is *not* merely a by-
product of a preference for large buttocks. In our critical test, we showed men multiple
women whose buttocks stuck out the exact same amount, but for different morphological
reasons (e.g., large buttocks vs. spinal curvature). The men showed a strong tendency to
prefer women whose buttock protrusion resulted from these spinal structures, not the
women with larger buttocks.

• Dr. Lewis: I hope that readers take away a new piece of knowledge, one that is distinct from
what many people thought they knew (i.e., a male preference for big buttocks as opposed to
a male preference for spinal curvature). I also hope they see that an evolutionary approach is
one that can inform our understanding of the world around us in new ways. Lastly, I hope
that all women who read this study recognize that in no way does this mean that a woman
must have a particular angle of lumbar curvature in order to be beautiful. Our research
shows that lumbar curvature has an influence on women’s attractiveness, but a closer
examination of the data also shows that many women who do not have an ideal angle of
lumbar curvature can still seen as very beautiful.

this study?
• Dr. Lewis: Our research establishes a previously undiscovered standard of attractiveness
based on spinal structures, but it does not eliminate the possibility of a true male preference
for female buttock size. There are many cultural anecdotes tied to buttock size, and some
recent research suggests that fat deposition in this region of the body would have been
associated with reproductive benefits. However, there is a relative absence of rigorous
scientific investigation of men’s psychology regarding this region of the female body. I hope
that we see an increase in good science that provides true tests of what we believe to be
true. We may find out that we were right, or wrong — or we may discover something new
altogether. Good science can offer all three.
• Citation:
• Lewis DMG, Russell EM, Al-Shawaf L, Buss DM. Lumbar curvature: a previously undiscovered
standard of attractiveness. Evolution and Human Behavior. 2015.
• MedicalResearch.com Interview with: Dr. David M.G. Lewis, PhD (2015). Curvy Bottoms
Linked To Pregnancy Advantage

Nanobody May Make Noroviruses Self Destruct
Dr. Grant Hansman
CHS Research Group at CellNetworks Heidelberg University and DKFZ
Deutsches Krebsforschungszentrum Heidelberg Germany
Dr. Hansman: Human noroviruses are the major cause of outbreaks of acute gastroenteritis.
There are several promising vaccine candidates. Vaccines may offer some protection, but the
fact that the virus changes every other year produces a challenge. Therefore, my research
group investigates the possibility to produce universal antivirals targeting conserved regions
on the virus capsid.
• We found that a Nanobody was able to bind with a high affinity, and broad reactivity to
diverse norovirus types. The Nanobody binding on the virus capsid caused the virus particles
to disassemble. The disassembly of the particles may render the virus non-infectious and
block viral infections.
• Dr. Hansman: At the moment, we are not ready to test in humans, but with further
development and testing, we hope to provide a proof-of-concept in surrogate norovirus
systems, since human norovirus cannot be grown in cell culture. A lot of work will be
required before any clinical trials, but for now, we have the potential to modify the Nanobody
for preclinical testing.

Nanobody May Make Noroviruses Self Destruct
Dr. Grant Hansman
CHS Research Group at CellNetworks Heidelberg University and DKFZ
Deutsches Krebsforschungszentrum Heidelberg Germany
this study?
• Dr. Hansman: We need optimize the binding to animal models and determine the effects in
these systems. We have to work out ways to deliver the Nanobody in order to give the most
effective treatment
• Citation:
• Nanobody Binding to a Conserved Epitope Promotes Norovirus Particle Disassembly
J Virol. 2015 Mar 1;89(5):2718-30. doi: 10.1128/JVI.03176-14. Epub 2014 Dec 17.
Koromyslova AD1, Hansman GS2.

Law Brings More Student Athletes To ER For Sports-Related Concussions
Dr. Pina Violano, RN, PhD
Trauma Department, Yale-New Haven Hospital, Injury Free Coalition for Kids of New Haven
Yale-New Haven Children’s Hospital New Haven 06510, CT
• Dr. Violano: In July of 2012, Connecticut became one of the first states to enact legislation to
ensure the safety and appropriate evaluation and management of sports-related concussions
(SRC) among High School students. SRCs are a common occurrence in high school sports with
their diagnosis increasing over the last decade. While the exact reasons are not known, public
health campaign efforts and education may have facilitated improvement in the evaluation
and detection of sports-related concussions and may have contributed to increase awareness
and treatment.
• Dr. Violano: Evaluation of two emergency department records revealed a marked increase in
the frequency of high school student athletes being treated for sports-related concussions
after the implementation of Connecticut’s SRC law. This suggests that Connecticut’s
legislation is effective in improving the evaluation and detection of sports-related
concussions in high school students.

• Dr. Violano: State concussion laws are a safety net to ensure that student athletes are
protected from further harm after sports-related concussions and require that they get the
appropriate evaluation and treatment. While the current law pertains only to student
athletes participating in Connecticut Interscholastic Athletic Conference (CIAC) sponsored
athletics, ALL athletes with a sports-related concussion who participate in organized sports at
all levels could benefit from the same standard of care by healthcare professionals trained in
the evaluation and management of concussions.

this study?
• Dr. Violano: Recommendations to expand the law to include youth level sports should be
perused.
• The numbers of youth athletes with sports-related concussions are presenting to the ED are
increasing, but further expansion of the state laws to youth sports should be considered for
future research. Our study showed that this legislation does not cause a residual increase in
presentation of sports-related concussions to the ED in other age groups. We have identified
that the law is not affecting summer sports-related concussion visits.
• Changes to state concussion laws could include summer camps, travel teams and all-star
teams to ensure that all children with sports-related concussions are getting appropriate care
and education. Concussion laws mandating the removal of athletes with a head injury from
play might be expanded to include all organized sports at all levels.
• Citation:
• The Effects of a State Concussion Law on the Frequency of Sport-Related Concussions as Seen
in Two Emergency Departments
• Thomas Trojian1*, Pina Violano23, Matthew Hall4 and Charles Duncan5
• Injury Epidemiology 2015, 2:2 doi:10.1186/s40621-015-0034-7 Published February 2015

Study Suggests Need For Long Term Follow Up Of Monoclonal Gammopathy
Prof. Sigurdur Y Kristinsson
Professor of Hematology
University of Iceland
• Prof. Kristinsson: Multiple myeloma is always preceded by a precursor condition called monoclonal
gammopathy of undetermined significance (MGUS). MGUS is characterized by a detectable
monoclonal protein in persons without evidence for end-organ damage or other related plasma cell
or lymphoproliferative disorders. MGUS is very common and is detected in approximately 5 percent
of persons 70 years or older. However, only a small proportion of MGUS progresses to a malignant
disorder, in fact the annual risk of progression to multiple myeloma or other related disorders is on
average 1 percent, with varying risks according to risk groups. Current guidelines suggest,
depending on the individual patient’s clinical risk score, life-long monitoring of MGUS individuals to
detect progression to multiple myeloma or related disorders. At this time, the impact of annual
monitoring on the outcome of patients who eventually develop multiple myeloma is unclear.
• Using high-quality population-based data from Sweden, we estimated the impact of prior
knowledge of MGUS diagnosis and comorbidities on multiple myeloma survival, by performing a
large population-based study using data on more than 14,000 multiple myeloma patients
diagnosed in Sweden 1976-2005, with follow-up through 2007. The hypothesis that detection and
follow-up of MGUS may influence survival in multiple myeloma is unlikely to ever be tested in a
prospective clinical study due to the large sample size required with long follow-up time, and
consequent extreme costs.
• We found that multiple myeloma patients with prior knowledge of MGUS had significantly 15%
better survival, despite having significantly more comorbidities. Interestingly, low-risk MGUS (with
very low M-protein) had highest risk of death. The observation that low M-protein concentration at
MGUS diagnosis was associated with poorer multiple myeloma survival may reflect less frequent
clinical follow-up. Our observations stress the importance of clinical follow-up in MGUS, regardless
of risk stratification.

• Prof. Kristinsson: Our results reflect the importance of life-long follow-up for individuals
diagnosed with MGUS, independent of risk score and highlight the need for better risk
models based on the biology of the disease. Patients should receive balanced information
stressing both the overall very low risk of progression to malignant disease but also what
symptoms could signal such development and the need of consulting their physician. The
higher prevalence of comorbid conditions in multiple myeloma patients with prior MGUS
knowledge supports that MGUS most often is diagnosed during follow-up for unrelated
conditions. Our findings raise the question whether screening for MGUS in the general
population could translate into earlier detection and treatment of multiple myeloma and lead
to better multiple myeloma survival.

this study?
• Prof. Kristinsson: Our results highlight the need for better risk models based on the biology
of multiple myeloma and MGUS. Also the impact of screening needs to be studied and
discussed and importantly, the impact of comorbidity on outcome in multiple myeloma
should be studied.
• Citation:
• Sigurdardottir E, Turesson I, Lund S, et al. The Role of Diagnosis and Clinical Follow-up of
Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma.
JAMA Oncol. Published online March 05, 2015. doi:10.1001/jamaoncol.2015.23.

Healthy Vegetarian Diet May Reduce Risk of Colon Cancer
Michael J. Orlich, MD, PhD
Program Director, Preventive Medicine Residency Loma Linda University
Co-Investigator, Adventist Health Studies
• Dr. Orlich: Colorectal cancer is the second leading cause of death from cancer in the United
States. Screening efforts such as colonoscopies have helped save many lives by detecting
pre-cancerous polyps and removing them. However, it is even better to prevent cancers from
forming in the first place. We call this primary prevention. Diet is a potentially important
approach to reduce the risk of developing colorectal cancer. In this analysis, we compared
those eating different categories of vegetarian dietary patterns to those eating a non-
vegetarian diet. About half of our study population was classified as non-vegetarian, which
we defined as eating meat at least weekly. The other half of our population we called
vegetarian and further divided them into four different vegetarian groups: semi-vegetarians
ate meat but less than once per week; pesco-vegetarians ate fish but avoided other meats;
lacto-ovo-vegetarians avoided meat but ate eggs and/or dairy products; and vegans avoided
all meats, eggs, and dairy. All vegetarians together had on average a 22% relative reduction
in the risk of developing colorectal cancer, compared to non-vegetarians, after carefully
adjusting for many other factors. Pesco-vegetarians in particular had a much lower risk
compared to non-vegetarians.

• Dr. Orlich: People consuming healthy vegetarian diets may have a lower risk of colorectal
cancer than non-vegetarians. Our vegetarians not only ate less meat than the non-
vegetarians, but also less sweets, snack foods, refined grains, and caloric beverages and more
fruits, vegetables, avocados, whole grains, beans, and nuts. Prior evidence strongly links
eating red and processed meat to a higher risk of colorectal cancer and fiber-rich foods to a
lower risk.

this study?
• Dr. Orlich: We plan to examine the relationship of several specific foods to colorectal cancer
risk in our population. Further research into mechanisms linking diet to colorectal cancer is
important. Interesting possibilities could include how dietary factors may alter the
expression of certain genes or how they may affect the many microbes that inhabit the large
intestine and the effects that such changes may have on cancer development. There is also a
need for improved methods for accurately measuring long-term diet in large numbers of
people.
• Citation:
• Orlich MJ, Singh PN, Sabaté J, et al. Vegetarian Dietary Patterns and the Risk of Colorectal
Cancers. JAMA Intern Med. Published online March 09, 2015.
doi:10.1001/jamainternmed.2015.59.

Male Occupation and Health Can Affect Fertility
MedicalResearch.com Interview with: Michael L. Eisenberg, M.D.
Director, Male Reproductive Medicine and Surgery
Assistant Professor Department of Urology
Stanford University School of Medicine
Dr. Eisenberg: There has been growing data that a man’s overall health may impact his
fertility. As such, we wanted to explore this link using the NICHD LIFE Study which has the
unique ability to account for both health and work exposure in men with both normal and
abnormal fertility. We found that certain aspects of a man’s work and health can impact his
semen parameters.
• Dr. Eisenberg: We have identified potentially modifiable factors which can provide future
targets for studies to improve a man’s fertility.
this study?
• Dr. Eisenberg: These associations should be explored in other populations. In addition,
further work is necessary to be able to understand how a health ailment can impact fertility.
• Citation:
• Michael L. Eisenberg, Zhen Chen, Aijun Ye, Germaine M. Buck Louis. Relationship between
physical occupational exposures and health on semen quality: data from the Longitudinal
Investigation of Fertility and the Environment (LIFE) Study. Fertility and Sterility, 2015; DOI:
10.1016/j.fertnstert.2015.02.010

New Mechanism Driving Lung Cancer Elucidated
Jean-Bosco Tagne Ph.D.
Assistant Professor of Medicine
Boston University School of Medicine; Pulmonary Center Boston, MA
Response: The lung transcription factor Nkx2-1 is an important gene regulating lung formation,
and normal respiratory functions after birth. Alteration in the expression of this transcription
factor can lead to lung interstitial disease, postnatal respiratory distress and lung cancer.
MicroRNAs repress gene expression, also controlling lung cell differentiation. In this study, we
characterized miRNAs regulated by Nkx2-1 in lung cells by genome-wide analysis and confirm the
expression patterns of highly regulated miRNAs in normal lung and in lungs lacking functional
Nkx2-1. By in vitro studies in lung cell lines we found that down-regulation of Nkx2-1 de-
represses miR-200c. Increased miR-200c, in turn, reduces the expression of its predicted targets
Nfib and Myb. These findings add new components to the gene regulatory network controlled by
Nkx2-1 in lung epithelial cells that may have implications in the various roles of Nkx2-1 in
development and disease particularly in this case lung cancer where the levels are seriously
altered.

New Mechanism Driving Lung Cancer Elucidated
Jean-Bosco Tagne Ph.D.
Assistant Professor of Medicine
Boston University School of Medicine; Pulmonary Center Boston, MA
this study?
• Response: As the regulatory mechanisms studied in this project are linked to tumor
suppression our findings have the potential to contribute to the control of lung tumor
formation. We are now using the results from this study to evaluate mechanisms of
prevention and treatment in a lung cancer model with the hope of improving disease
outcomes. We are testing a novel drug delivery system developed in our laboratory using a
Nano Emulsion Technology to target-deliver miRNAs such as miR-200c into cancer cells to
inhibit its predicted targets Nfib and Myb, two strong oncogenes.
• Citation:
• Transcription factor and microRNA interactions in lung cells: an inhibitory link between NK2
homeobox 1, miR-200c and the developmental and oncogenic factors Nfib and Myb
• Respir Res. 2015; 16(1): 22.
• Published online 2015 Feb 13. doi: 10.1186/s12931-015-0186-6
• Jean-Bosco Tagne, Omar R Mohtar, Joshua D Campbell, Meenakshi Lakshminarayanan,
Jingshu Huang, Anne C Hinds, Jining Lu, and Maria I Ramirez

High Testosterone Low Estrogen Linked To Men’s Cardiovascular Health
Elaine W. Yu, MD, MMSc Assistant Professor of Medicine
Harvard Medical School Massachusetts General Hospital
MGH Endocrine Unit
Dr. Yu: It is well known that cardiovascular disease is more common in men than in
women. The exact reasons for this are unknown, but may be related to gender differences in
levels of sex hormones such as testosterone and estrogen. As compared to premenopausal
women, men have higher testosterone and lower estrogen levels. It is currently unclear
whether the actions of testosterone and/or estrogen affect cardiovascular risk factors.
• In this study, we explored the regulation of cardiovascular risk factors by testosterone and
estrogen in men. We found that higher levels of testosterone led to lower HDL levels (“good”
cholesterol), whereas estrogen did not regulate HDL. In contrast, low levels of estrogen led
to worsening insulin resistance and increased muscle fat, markers for developing
diabetes. Importantly, LDL cholesterol (“bad” cholesterol”) was not affected by either
testosterone or estrogen in men.
• Dr. Yu: This study of adult men revealed that HDL levels are regulated by testosterone and
unaffected by estrogen, whereas insulin resistance and muscle fat are regulated by estrogen
but not testosterone. These observations may help explain why men have a higher risk of
cardiovascular disease than women.

High Testosterone Low Estrogen Linked To Men’s Cardiovascular Health
Elaine W. Yu, MD, MMSc Assistant Professor of Medicine
Harvard Medical School Massachusetts General Hospital
MGH Endocrine Unit
this study?
• Dr. Yu: It will be important to evaluate whether other cardiovascular risk factors are similarly
regulated by gonadal steroids in men. For example, we plan to study effects of testosterone
and estrogen on inflammatory markers as well as hormones related to fat metabolism and
cardiovascular function. An improved understanding of these effects may help to explain sex
differences in cardiovascular disease.
• Citation:
• ENDO15 Abstract discussing:
• Men’s heart disease risk linked to high testosterone and low estrogen
• MedicalResearch.com Interview with:Elaine W. Yu, MD, MMSc Assistant Professor of
Medicine Harvard Medical School (2015). High Testosterone Low Estrogen Linked To Men’s
Cardiovascular Health

Clinical Breast Exams May Be Improved By Integrating Sensors
Carla M. Pugh, M.D., Ph.D. FACS
Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program
Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine
and Public Health, Madison, W
Dr. Pugh: The clinical breast examination is routinely performed on millions of women each year. It is used
for screening breast cancer and is also routinely performed on women presenting with symptomatic
breast conditions.
• In this study we assessed the performance of the clinical breast examination among a large sample of
practicing physicians. There were two main goals to the study. The first goal was to identify current
recommendations for performing the clinical breast examination and investigating how this relates to
examination sensitivity or finding a mass. The second and more general goal was to develop a method for
objective assessment of clinical skills.
• Novel clinical breast examination simulators were used in this study; in addition to their ability to present
different pathologies and multiple clinical scenarios, they were all integrated with advanced force sensors.
These sensors include approximately 2000 discrete sensing elements, measuring force level and
distribution thought the breast examination. These sensors provide information at a level of detail that is
not possible with observation alone.
• Four models were used in this study; two models presenting superficial soft masses and two models
representing hard chest wall masses. The study was performed from 2013 to 2014 with 553 physicians
performing the clinical breast examination on our models. The participants were recruited at three annual
clinical meetings: 136 at the American Society of Breast Surgeons, 236 at the American Academy of Family
Physicians, and 181 at the American College of Obstetricians and Gynecologists.
• The study found a significant relationship between the force used during palpation and the accuracy of the
assessment of the deep-tissue lesions. More specifically, the study found that some physicians don’t apply
enough force during the examination putting them at high risk of missing deep-tissue lesions. Since force
can’t be measured by human observation this underscores the added value of integrating sensors into
clinical simulators.

Clinical Breast Exams May Be Improved By Integrating Sensors
Carla M. Pugh, M.D., Ph.D. FACS
Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program
Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine
and Public Health, Madison, W
• Dr. Pugh: Clinicians and patients should be aware that while gentle patting of the breast
might find superficial masses, more force is typically needed for finding deep-tissue lesions.
The amount of force will depend on factors such as breast density and size and should be
adjusted as such. This high risk practice of light patting was found at all levels of experience.
Some physicians will need to change and improve the clinical breast examination techniques
they have been using for many years.

Medical research slideshare_march 12_2015

Medical research slideshare_march 12_2015

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