MedicalResearch.com Top Interviews September 5 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
Sept 3 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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Sublingual Immunotherapy Not Currently Recommended For Asthma Control
MedicalResearch.com Interview with: Rebecca Normansell MA MB Bchir Cochrane Airways Population Health
Research Institute
St George’s, University of London
 Medical Research: What is the background for this study?
 Response: Asthma is a common, long-term, respiratory condition which affects over
300 million people worldwide. It is a burden not only for the individual with asthma but
also for the health services that care for them and the wider economy, due to days
lost from work and school.
 Asthma therapies aim to prevent attacks and improve symptoms by reducing airway
constriction and inflammation, but they come with their own risks of side effects. For
example, long-term high-dose inhaled corticosteroids have been associated with
growth restriction in children and long-acting beta2-agonists as mono-therapy have
been associated with increased risk of death in people with asthma.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

Research Institute
 There is growing interest in developing novel treatments for asthma and one such
treatment is specific allergen immunotherapy. Immunotherapy has the potential to be
a useful approach for asthma as it is thought that for approximately half of people
with asthma, allergies are an important trigger for their symptoms and attacks.
Immunotherapy can be delivered by injection (subcutaneously) or under the tongue
(sublingually) and aims to bring about immune tolerance.
 Immunotherapy has already been demonstrated to be effective in certain conditions,
such as allergic rhinitis and wasp and bee sting allergy, but its effectiveness and
safety in asthma is less clear. In fact, immunotherapy is not recommended at all for
use in people with severe or uncontrolled asthma due to the risk of triggering a
serious respiratory reaction.

Research Institute
 Medical Research: What are the main findings?
 Response: Our review looked for trials in which people with asthma who were given
sublingual immunotherapy (SLIT) were compared with those given placebo, or who
continued usual asthma care. We found 52 randomised controlled trials which met
our inclusion criteria, allocating over 5,000 people to either SLIT or placebo/usual
care. Most of the participants had mild asthma and were allergic to either house dust
mite or pollen.
 Despite the large number of eligible trials we were only able to perform a limited
meta-analysis. This is because most of the trials did not report the efficacy outcomes
we were most interested in: exacerbations and quality of life. Asthma symptoms and
medication use were both more frequently reported, but often using different, un-
validated scales so we did not perform a meta-analysis for these outcomes.

Research Institute
 However, we were able to combine serious adverse event data from 22 trials
involving 2560 participants and data for all adverse events from 19 trials including
1755 participants. SLIT did not appear to be associated with an increased risk of
serious adverse events, although very few events were observed overall. SLIT was
associated with a small increase in the risk of all adverse events, which in absolute
terms equated to an increase from 222 per 1000 people in the control group to 327
per 1000 (95% confidence intervals 257 to 404). Importantly, many of these events
were mild and transient local reactions and did not generally result in participants
withdrawing from the trial.

Research Institute
 Medical Research: What should clinicians and patients take away from your
report?
 Response: Sublingual immunotherapy is not currently recommended for the
treatment of asthma. This is partly due to a lack of convincing evidence about efficacy
and, perhaps more importantly, due to safety concerns. Our review supports this
position as we cannot draw any clear conclusions about how well SLIT works for
asthma and we cannot be at all sure that what we found about serious adverse
events would apply to those with more severe asthma. As a result, confidence in our
findings is generally low.

Research Institute
 Medical Research: What recommendations do you have for future research as
a result of this study?
 Response: The global burden of asthma makes the quest for new, safe treatments a
priority. SLIT has the potential to be a useful tool in asthma treatment. However, our
review is limited by the infrequent reporting of exacerbations and quality of life, both
of which are important outcomes for patients and policy makers. The use of varied,
un-validated symptom and medication scores also meant we could not sensibly
combine results in a meta-analysis. In the future, it would be helpful for trialists to use
standardised, validated scales wherever possible and to report important events,
such as exacerbations, even if they are very rare.
 Citation:
 Cochrane Library
(http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011293.pub2/full) Normansel
l R, Kew KM, Bridgman AL. Sublingual immunotherapy for asthma. Cochrane
Database of Systematic Reviews 2015, Issue 8. Art. No.: CD011293. DOI:
10.1002/14651858.CD011293.pub2.

A Pint of Water Before Meals May Speed Weight Loss
MedicalResearch.com Interview with: Dr Helen Parretti NIHR Clinical Lecturer
University of Birmingham
 Dr Parretti: Drinking water is widely advocated as a useful tool in weight loss and is
included in many weight loss programs, yet there is little evidence to support this in
practice. Some initial small laboratory studies suggested drinking water before main
meals might help with weight loss, but we didn’t know whether it would work in an
everyday setting over a sustained period of time.

 Dr Parretti: We recruited 84 people into the trial. 41 in the “preloading water” group
and 43 in the comparator group. The people in the preloading water group were
asked to drink 500ml (around 1 pint or 2 glasses) of water 30 minutes before each
main meal and lost, on average 1.3kg (2.87lb) more than those in the comparator
group over 12 weeks. Those who reported preloading before all three main meals in
the day reported a loss of 4.3kg (9.48lbs) over the 12 weeks, whereas those who only
preloaded once, or not at all, only lost an average of 0.8kg (1.76lbs).

report?
 Dr Parretti: We believe that drinking 500ml of water before main meals is a simple
message that could easily be given by healthcare professionals to patients with
obesity when they are giving weight loss advice. When combined with brief
instructions on how to increase your amount of physical activity and on a healthy diet,
it seems to help people to achieve some extra weight loss – at a moderate and
healthy rate.
 Just drinking about a pint of water, three times a day, before your main meals may
help reduce your weight and it’s something that doesn’t take much work to integrate
into our busy everyday lives

 Dr Parretti: We would like to carry out a larger trial with 12 month follow up to allow
us to gain more definitive evidence that water preloading is effective and also to
investigate the potential mechanisms of action more fully. We are now looking to
gain funding to carry out this research.
 Citation:
 Helen M. Parretti, Paul Aveyard, Andrew Blannin, Susan J. Clifford, Sarah J.
Coleman, Andrea Roalfe, Amanda J. Daley. Efficacy of water preloading before main
meals as a strategy for weight loss in primary care patients with obesity:
RCT. Obesity, 2015; DOI: 10.1002/oby.21167

Depression Risk Not Raised After Unsuccessful Fertility Treatments
MedicalResearch.com Interview with:
Camilla Sandal Sejbaek PhD Department of Public Health
University of Copenhagen
 Medical Research: What is the background for this study? What are the main
findings?
 Response: Previous literature have shown ambiguous results when investigating the
association between becoming a mother and depression among women in fertility
treatment. Small questionnaire-based studies with self-reported depression have
shown that women in unsuccessful fertility treatment had a higher risk of depressive
symptoms compared to women in successful fertility treatment. Two larger register-
based studies using clinical depression (depression diagnosed at the psychiatric
hospitals) have shown that women becoming a mother are at increased risk of clinical
depression.

Our findings, from a large register-based study with about 41,000 women in assisted
reproductive technology (ART) treatment, showed that women WHO became mothers
had a higher risk of clinical depression compared to women in ART treatment WHO did
not become mothers. The risk of clinical depression were more than five-fold higher
within the first 6 weeks after becoming a mother to a live-born child.

report?
 Response: Clinicians working with fertility patients and the patients themselves
should be reassured that women in assisted reproductive technology treatment and
who do not become mothers are not at increased risk of a clinical depression. It is
sad to go through fertility treatment and not have your wish fulfilled, but our findings
suggest that these women are not at increased risk of a clinical depression compared
to women who do become mothers.

 Response: I think it would be very interesting to investigate depression more broadly
among women in assisted reproductive technology treatment and fertility treatment
as a whole. Furthermore, I think it could be interesting to investigate if the risk of
clinical depression among women in ART treatment is the same as in a background
population.
 Citation:
 Acta Obstet Gynecol Scand. 2015 Aug 3. doi: 10.1111/aogs.12705. [Epub ahead of
print]
 Are repeated assisted reproductive technology treatments and an unsuccessful
outcome risk factors for unipolar depression in infertile women?
 Sejbaek CS1, Pinborg A2, Hageman I3, Forman JL4, Hougaard CØ1, Schmidt L1.

miRNA-based Blood Test May Detect Early Pancreatic Cancer MedicalResearch.com Interview with: Jenny
Permuth Wey, PhD, MS Assistant Member
Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer Center
findings?
 Dr. Wey: Pancreatic cancer is one of the deadliest cancers world-wide. It is currently
the fourth leading cause of cancer-related deaths in the United States, and is
predicted to become the second leading cause by 2030. Currently there are no
accurate methods to diagnose pancreatic cancer early when a patient may be eligible
for surgery to remove the tumor and hopefully survive longer. To beat this disease,
early detection is key, and our team has dedicated efforts to studying pancreatic
cancer in its ‘precancerous’ state because we and other researchers believe that the
identification and treatment of precancerous pancreatic lesions offers a promising
strategy to reduce the number of people losing their lives to this disease.

Similar to how colon polyps can progress into colon cancer, we now know that certain
types of pancreatic cystic lesions can progress into pancreatic cancer. Pancreatic cancer
precursors/pre-cancers known as intraductal papillary mucinous neoplasms (IPMNs)
account for nearly one-half of the estimated 150,000 asymptomatic pancreatic cysts
detected as ‘incidental findings’ on computed tomography (CT) scans or magnetic
resonance imaging (MRI) scans each year during the clinical work-up for an unrelated
condition. Imaging alone cannot reliably distinguish between benign, pre-cancerous, and
cancerous cysts, and cannot differentiate ‘low-risk’intraductal papillary mucinous
neoplasms‘ (defined as low- or moderate-grade disease) that can be monitored from
‘high-risk’ IPMNs (defined as high-grade or invasive disease) that should be surgically
removed. The decision to undergo pancreatic surgery is not trivial for the patient and
medical team since pancreatic surgery can be associated with an estimated 40% chance
of complications and a 4% chance of death. Noninvasive tests are needed to accurately
detect precancerous lesions of the pancreas so that personalized risk assessment and
care can be provided.

microRNAs (miRNAs) are small molecules that act as ‘master-regulators’ of cancer-
related processes in the body. One of the main purposes of our ‘proof of principle’ study
was to measure miRNAs in the blood and determine whether a set of miRNAs could
distinguish patients with IPMNs from healthy individuals. We then sought to determine
whether a set of miRNAs could distinguish patients known to have ‘low-risk’ IPMNs from
those with ‘high-risk’ IPMNs. We show that new, relatively inexpensive digital technology
could reliably measure miRNAs in blood plasma (the pale yellow liquid component of
blood) from individuals newly-diagnosed with pancreatic cancer precursors (IPMNs) and
healthy individuals. Thirty miRNAs out of 800 tested showed higher levels in IPMN
patients compared to healthy individuals, providing a preliminary ‘miRNA signature’ that
may be found only in people with early pancreatic disease, suggesting it could serve as
an early diagnostic tool. Furthermore, we also provide preliminary data to suggest that a
5-miRNA signature can partially distinguish high-risk IPMNs that warrant resection from
low-risk IPMNs that can be watched. This is important clinically because it would be
opportune to personalize care such that high-risk IPMNs that warrant resection are
properly identified while individuals with low-risk IPMNs are spared the substantial risks
of mortality and morbidity associated with overtreatment from unnecessary surgery.

report?
 Dr. Wey: This is promising news and could someday lead to a noninvasive test for
early detection of this disease. This could translate into earlier diagnoses and lives
saved. However, It is important to note that the results presented in this study are
preliminary. Additional research is needed to determine if such a miRNA-based blood
test could help diagnose pancreatic cancer earlier or more effectively than current
methods. These results need to be verified in a larger prospective, or forward-
looking, study before being available for use in the clinical setting. This could take
several years and will involve pancreatic cancer researchers working together with
patients and families affected by this disease.

Departments of Cancer Epidemiology and Gastrointestinal Oncology Moffitt Cancer Center Medical Research: What recommendations do you have for future research as a
result of this study?
 Dr. Wey: Findings from this proof of principle study support further development of a
miRNA-based blood test to detect precancerous lesions in the pancreas. Large-scale
studies with rigorous designs are needed to further explore the potential for miRNAs to be
utilized clinically as markers for the early detection of pancreatic cancer.Through recently-
obtained funding from the State of Florida and the newly established Florida Academic
Cancer Center Alliance, our team at Moffitt Cancer Center plans to further our research on
IPMNs by partnering with researchers from the University of Florida Health Cancer Center
and the University of Miami/Sylvester Comprehensive Cancer Center. This new
partnership, called the Florida Pancreas Collaborative, representsthe first state-wide multi-
cancer center collaboration we are aware of that is dedicated to conducting research on
IPMNs with the ultimate goal of promoting the prevention and early detection of pancreatic
cancer.

 Citation:
 “Plasma MicroRNAs as Novel Biomarkers for Patients with Intraductal Papillary Mucinous
Neoplasms of the Pancreas.” Cancer Prev Res Published OnlineFirst August 27, 2015;
DOI: 10.1158/1940-6207.CAPR-15-0094

Developed Countries More At Risk of Harboring Polio Virus Excreters
MedicalResearch.com Interview with: Dr Javier Martin PhD Principal Scientist Division of Virology
National Institute for Biological Standards and Control (NIBSC)
Medicines and Healthcare products Regulatory Agency (MHRA)
United Kingdom
 Dr. Martin: The global eradication of polio appears to be within reach. There has
been no case of poliomyelitis caused by circulating wild type 2 poliovirus since 1999,
no case of type 3 since November 2012 and the last case of type 1 in Africa was in
August 2014, leaving some areas of Pakistan and Afghanistan as the main remaining
reservoirs of circulating wild type 1 poliovirus. Poliovirus strains in the live-attenuated
oral polio vaccine (OPV) are known to quickly revert to neurovirulent phenotype
following replication in humans after immunisation. These vaccine-derived poliovirus
(VDPV) strains can transmit from person to person in populations with low immunity
potentially leading to poliomyelitis outbreaks.

United Kingdom
 Dr. Martin: Vaccine-derived poliovirus strains can replicate for very long periods of
time in hypogammaglobulinaemic immunodeficient individuals. The case described in
our paper represents by far the longest period of excretion described from such a
patient and the only identified individual known to be excreting highly evolved VDPVs
at present. As these viruses have lost the attenuation properties of the original
vaccine strains, they could potentially cause poliomyelitis in susceptible people so it is
very important to maintain high levels of vaccine coverage and surveillance activities.
This is particularly important at this end stage of the global polio eradication initiative
and will continue for some time after eradication as we want to minimise the risk of
polio coming back. Results from our research will help designing optimal strategies
for the polio eradication endgame which includes improved surveillance methods to
quickly detect and characterize poliovirus from clinical and environmental samples
and vaccination schemes and antiviral treatments to complete eradication and
minimize the risk for a polio comeback.

United Kingdom
report?
 Dr. Martin: There are two efficient vaccines against polio, OPV, referred above, and
inactivated polio vaccine (IPV). These vaccines protect humans from paralytic
poliomyelitis caused by all known poliovirus strains and variants. Immunodeficient
individuals should be assessed and if necessary tested for poliovirus excretion.
Treatment with immunoglobulin as usually prescribed to these patients will confer
high levels of protection against paralytic disease. As patients such as the one
described here will have less chance to survive in some developing countries with
lack of medical treatment, middle income and developed countries are more at risk of
harbouring chronic polio virus excreters. Indeed, several highly drifted VDPV strains
have recently been isolated from sewage samples in Slovakia, Finland, Estonia and
Israel indicating that an unknown number of these chronic excreters exist elsewhere.
Populations with high vaccination coverage are protected against disease caused by
these viruses as they are against any known poliovirus strains.

United Kingdom
 Medical Research: What recommendations do you have for future research as a
 Dr. Martin: Virus isolates from this individual should be further characterised to better
understand the population dynamics of poliovirus evolution in immunodeficient individuals.
This will help assessing the effectiveness of current anti-viral methods and methods in
development to interrupt virus replication in these patients. Enhanced surveillance
including sewage sampling should continue for as long as possible to search for the
presence of VDPV strains such as those described in our paper. Eventually, new polio
vaccines such as those based on non-infectious virus-like particles or even new genetically
designed stable live-attenuated versions with no associated risk of producing VDPVs might
be required to complete polio eradication. Scientists at NIBSC and other leading
laboratories around the world are actively working on the development of such vaccine
candidates.
 Citation:
 Glynis Dunn, Dimitra Klapsa, Thomas Wilton, Lindsay Stone, Philip D. Minor, Javier Martin.
Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on
the Global Polio Eradication Initiative. PLOS Pathogens, 2015; 11 (8): e1005114
DOI:10.1371/journal.ppat.1005114

May Be Time To Stop Counting Calories
MedicalResearch.com Interview with: Dr Aseem Malhotra MBChB, MRCP
Honorary Consultant Cardiologist – Frimley Park Hospital
Consultant Clinical Associate to the Academy of Medical Royal Colleges
findings?
 Dr. Malhotra: It is a review of all the research up to date on what is the impact of diet
on health. What type of diet has the most robust evidence for weight and health and
how this can be translated into policy to rapidly reduce the burden of chronic disease.

report?
 Dr. Malhotra:
 That “low fat” diets to do not improve health outcomes and the public should
 stop counting calories.
 That a high fat Mediterranean diet is more powerful in reducing the risk of
 heart attack and stroke than any medical treatment.
 That it’s effect is independent of cholesterol lowering.
 That rapid weight loss through calorie counting combined with exercise doesn’t
 only not improve health outcomes in the long term for diabetics but can also be
 potentially harmful by increasing CVD risk.

 Dr. Malhotra: Seeing the impact in real world populations of policy interventions that
include the taxing of sugary drinks, banning junk food advertising and increasing the
affordability of healthy foods.
 Citation:
 Aseem Malhotra, James J DiNicolantonio, Simon Capewell. It is time to stop counting
calories, and time instead to promote dietary changes that substantially and rapidly
reduce cardiovascular morbidity and mortality. Open Heart, 2015 DOI:
10.1136/openhrt-2015-000273

Working Memory Problems Can Persist Into Adulthood in Children with ADHD
MedicalResearch.com Interview with: Dr. Graham Murray PhD University Lecturer Department of Psychiatry
Addenbrooke’s Hospital
Cambridge UK
findings?
 Dr. Murray: There is debate about the extent to which ADHD persists into adulthood,
with estimates suggesting that between 10-50% of children still have ADHD in
adulthood. Diagnosis (whether in childhood or adulthood) is currently reliant on
meeting symptom checklists (such as the American Psychiatric Association’s
Diagnostic and Statistical Manual), and a current diagnosis is often the prerequisite to
access health care from psychiatric services. We decided to follow up a sample of 49
teens who all had a confirmed diagnosis of ADHD at age 16. We also followed a
control group made up of comparison healthy volunteers from the same social, ethnic
and geographical background.

Cambridge UK
When we used the symptom checklist criteria of persistence, only 10% of patients still
met ADHD diagnostic criteria in adulthood. However, there is more to ADHD than this.
When it comes to adult brain structure and function, it didn’t make any difference whether
symptom checklists were still met or not. On reaching adulthood, the adolescent ADHD
group show reduced brain volume in the caudate nucleus – a key brain region that
supports a host of cognitive functions, including working memory function. When we
assessed working memory ability, we noted persistent problems in the adolescent ADHD
group, with a third of the adolescent ADHD sample failing the memory test. The poor
memory scores seemed to relate to a lack of responsiveness in the activity of the
caudate nucleus that we could detect using functional MRI scans. In the control group,
when the memory questions became more difficult, the caudate nucleus became more
active, and this appeared to help the control group perform well; in the adolescent ADHD
group, the caudate nucleus kept the same level of activity throughout the test. It was as
if, for the controls, when the test got harder, the caudate nucleus went up a gear in its
activity, and this is likely to have helped solve the memory problems. But for
the adolescence ADHD group, the caudate couldn’t go up a gear when the test became
harder, and this likely resulted in poorer performance.

Cambridge UK
report?
 Dr. Murray: We should remember that there is more to ADHD than simply whether or
not a person meets diagnostic symptoms checklist criteria at any given time, and
need to remember that a holistic clinical assessment is important. Incorporating
memory tests into assessments in future clinical work and research studies could be
an option that might bring an additional clinical perspective, inform future treatment
and help in the planning and commissioning of healthcare services.

Cambridge UK
 Dr. Murray: It will be important to learn more about the impact of working memory
function on quality of life in adult ADHD, and to examine whether intensive cognitive
training or medication treatment can hep patients improve their memory function in
adulthood.
 Citation:
 Andres Roman-Urrestarazu, Päivi Lindholm, Irma Moilanen, Vesa Kiviniemi, Jouko
Miettunen, Erika Jääskeläinen, Pirjo Mäki, Tuula Hurtig, Hanna Ebeling, Jennifer H.
Barnett, Juha Nikkinen, John Suckling, Peter B. Jones, Juha Veijola, Graham K.
Murray. Brain structural deficits and working memory fMRI dysfunction in young
adults who were diagnosed with ADHD in adolescence. European Child & Adolescent
Psychiatry, 2015; DOI: 10.1007/s00787-015-0755-8

Borderline Personality Linked To Lack of Activity In Empathy Areas of Brain
MedicalResearch.com Interview with: Brian W. Haas, Ph.D. Assistant Professor Department of Psychology
University of Georgia
findings?
 Dr. Haas: We used a new way to study Borderline Personality Disorder. We studied
the traits associated with this condition in healthy people not diagnosed with
Borderline Personality Disorder. We found that people that possess more Borderline
Personality traits exhibit reduced brain activity in parts of the brain important for
empathy.
report?
 Dr. Haas: These findings contribute to existing models associating Borderline
Personality with abnormal interpersonal social function. One reason why borderline
traits may affect the way people socially related to others, may be because of the way
parts of the brain important for empathy function.

Borderline Personality Linked To Lack of Activity In Empathy Areas of Brain
MedicalResearch.com Interview with: Brian W. Haas, Ph.D. Assistant Professor Department of Psychology
University of Georgia
 Dr. Haas: Future research is necessary to investigate empathic processing in more
real-life naturalistic settings.
 Citation:
 Haas BW, Miller JD. Borderline Personality Traits and Brain Activity During Emotional
Perspective Taking. Personal Disord., 2015 [link]

Wild Blueberry Polyphenols May Help Fight Periodontal Disease
MedicalResearch.com Interview with: Daniel Grenier, Ph.D. Professeur titulaire
Oral Ecology Research Group, Faculty of Dentistry, and Institute of Nutrition and Functional Foods, Université Laval
Quebec City, QC, Canada
 Dr. Grenier: Periodontal diseases (gingivitis and periodontitis) are major public health
problems because of their high prevalence and incidence in all regions of the world.
According to epidemiological studies, approximately 5% of North Americans suffer
from severe generalized periodontitis, which can lead to tooth loss, while mild to
moderate periodontitis affects up to 35% of adults. Given emerging data indicating
that there is a relationship between periodontal diseases and systemic health
problems such as diabetes, cardiovascular diseases, and preterm birth, studies on
preventive and therapeutic strategies targeting periodontal diseases are highly
relevant.

 Dr. Grenier: Using various in vitro models, we brought clear evidence that a
blueberry extract enriched in proanthocyanidins can act on the two etiological
components of periodontal disease. We first showed that these polyphenols inhibit
the growth of Fusobacterium nucleatum as well as its ability to form a biofilm, which
can provide to the bacterium a resistance to antimicrobial agents and immune cells.
Interestingly, F. nucleatum has been associated with various forms of periodontitis as
well as to a number of extra-oral infections, including endocarditis, inflammatory
bowel disease, and brain abscesses. Moreover, the blueberry extract attenuated the
inflammatory response of human macrophages challenged with F. nucleatum,
resulting in a decreased secretion of inflammatory cytokines (IL-1β, IL-6, TNF-α) and
tissue destructive enzymes (MMP-8, MMP-9). Evidence was brought that this
property is likely related to the ability of the blueberry polyphenols to block the
activation of the NF-κB signaling pathway that play a key role in inflammatory
reactions.

Over the last decade, my laboratory has been investigating the potential benefits of
various classes of polyphenols for oral health. Polyphenols are a large group of natural
substances found in plants and characterized by the presence of more than one phenol
unit per molecule. Given that wild blueberries (Vaccinium angustifolium Ait), a popular
berry fruit in Quebec, are particularly rich in a specific class of polyphenols, called
proanthocyanidins, we tested their effect on the two major etiological factors involved in
the pathogenesis of periodontitis: a limited group of Gram negative anaerobic bacteria,
and an uncontrolled host immune response to these pathogens that results in the
secretion of high amounts of inflammatory mediators which modulate the progression and
severity of periodontitis.

report?
 Dr. Grenier: This dual anti-bacterial and anti-inflammatory action of wild blueberry
polyphenols suggests that they may be promising candidates for novel therapeutic
agents against periodontal diseases. However, results obtained in vitro are difficult to
transpose to the in vivo situation, since the oral environment could interfere with the
biological properties of these molecules. Consequently, clinical studies in this area
are warranted.

 Medical Research: What recommendations do you have for future research as a result of
this study?
 Dr. Grenier: Studies aimed to isolate and characterize the bioactive molecules found in the
blueberry extract are currently in progress. These molecules could then be used for localized
application into diseased periodontal sites, through irrigation or insertion of a slow-release drug
device. The bioactive molecules may also be incorporated into oral hygiene products (mouthrinse,
chewing gum, which could be tested in human clinical studies for their potential benefits in
preventing periodontal diseases.
 Studies in progress in my laboratory are also testing the polyphenols from the highbush blueberry
species (Vaccinium corymbosum) for similar properties as well as for their benefits against dental
caries.
 Citation:
 J Agric Food Chem. 2015 Aug 12;63(31):6999-7008. doi: 10.1021/acs.jafc.5b01525. Epub 2015
Aug 4.
 Wild Blueberry (Vaccinium angustifolium Ait.) Polyphenols Target Fusobacterium nucleatum and
the Host Inflammatory Response: Potential Innovative Molecules for Treating Periodontal
Diseases.
 Ben Lagha A1, Dudonné S1, Desjardins Y1, Grenier D1.

Microscopic Regression in Thin Melanoma May Be Good Prognostic Sign
MedicalResearch.com Interview with: Simone Ribero, M.D., Ph.D. University of Turin
Department of Medical Sciences Turin Italy and King’s College London
Department of Twin Research and Genetic Epidemiology
St Thomas’ campus London, UK
findings?
 Response: The histologic regression is a discussed feature and its prognostic role is
debated in literature. Our group has previously described a favorable prognostic role
of histological regression in stage I-II melanoma patients. Some clinicians still
perform Sentinel Lymph Node biopsy on the basis of regression in thin melanoma
considering this feature as able to underestimate Breslow Thickness.
 In this study we described in a metanalyses with more then 10000 melanoma
patients that histological regression is inversely associated with Sentinel Lymph Node
positivity.

report?
 Response: Clinicians should, on the basis of this study, interpret the regression as a
favorable factor, and don’t look at it as an increase risk of lymph node metastases.

 Response: Future research on molecular biology of regression are needed to
demonstrate what we clinically assist, so that regression could potentially be a
marker of immune system status in primary melanoma.
 Citation:
 Ribero S, Gualano M, Osella-Abate S, et al. Association of Histologic Regression in
Primary Melanoma With Sentinel Lymph Node Status: A Systematic Review and
Meta-analysis. JAMA Dermatol. Published online September 02, 2015.
doi:10.1001/jamadermatol.2015.2235.

Neurons In Brain Most Affected by Alcohol Identified MedicalResearch.com Interview with: Dr. Jun Wang
MD PhD, Assistant Professor
Department of Neuroscience and Experimental Therapeutics
Interdisciplinary Program in Neuroscience
Texas A&M College of Medicine
 Dr. Wang: Alcohol use disorder is a very common disease, but the mechanism is not clear
and the treatment is limited.
 Dr. Wang: We have three findings in an animal model of alcoholism:
 Alcohol drinking changes brain cells (also called neurons), making them more excitable.
 The change occurs only in a group of neuron called D1-neurons.
 Suppressing D1-neurons in a sub-region of the brain reduces excessive alcohol intake.

Neurons In Brain Most Affected by Alcohol Identified MedicalResearch.com Interview with: Dr. Jun Wang
MD PhD, Assistant Professor
Department of Neuroscience and Experimental Therapeutics
Interdisciplinary Program in Neuroscience
Texas A&M College of Medicine
 Medical Research: What should clinicians and patients take away from your report?
 Dr. Wang: Since our research was conducted in animals, whether it works in human is not
known. However, research indicates that a drug inhibiting dopamine D1 receptors might
help stop alcohol drinking.
 Dr. Wang: It would be of interest to find therapeutics to inhibit D1-neurons specifically in
the dorsomedial striatum, a sub-region of the brain where the study was conducted.
 Citation: Wang, Y. Cheng, X. Wang, E. Roltsch Hellard, T. Ma, H. Gil, S. Ben Hamida, D.
Ron. Alcohol Elicits Functional and Structural Plasticity Selectively in Dopamine D1
Receptor-Expressing Neurons of the Dorsomedial Striatum. Journal of Neuroscience,
2015; 35 (33): 11634 DOI: 10.1523/JNEUROSCI.0003-15.2015

Protein Keratin Promotes Cancer Growth and Chemotherapy Resistance
MedicalResearch.com Interview with: Kenneth R. Shroyer, MD, PhD The Marvin Kuschner Professor and Chair
Department of Pathology Stony Brook Medicine
Stony Brook, NY
findings?
 Dr. Shroyer: Patients that appear to have the same type of cancer often respond very
differently to treatment; while some patients appear to go into long-term regression or are
cured, others follow a rapid downhill course and ultimately die of their disease. This
suggests that there are fundamental differences between tumors at the biologic level that
are not detected by current clinical measures.
 In this study, we report the unexpected finding that cancer patients that have high levels of
a protein called Keratin 17 (K17) have decreased long-term survival when compared to
patients that express little to no K17 in their tumors. In addition, we found that K17 enters
the nucleus of tumor cells to mediate the degradation of the master regulator of cell division
and tumor growth key tumor suppressor protein, p27. Furthermore, we identified that K17
increases the resistance of tumor cells to chemotherapy.
 These are critical findings because this is the first report that a keratin is an oncoprotein
that can enter the nucleus to promote the development of cancer and resistance to
chemotherapy.

Stony Brook, NY
report?
 Dr. Shroyer: Overall, these results suggest that K17 could be used as a biomarker to
distinguish between “clinically identical” patients, identifying cases that are more
aggressive at the time of diagnosis and potentially guiding personalized treatment
based on individual K17 status.

Stony Brook, NY
 Medical Research: What recommendations do you have for future research as a result of this study?
 Dr. Shroyer: These findings provide insight into why cancer patients without K17 expression have better survival
probability compared to patients that have high K17 levels. Further studies, however, are needed to determine if
there are additional roles of K17 in cancer that extend far beyond its effect on p27. In addition, it is still not known
why some patients express K17 and others don’t; understanding what triggers K17 expression could one day help
us to elucidate more effective ways to treat cancer patients by targeting K17 expression and to potentially increase
the survival of patients with cancer.
 Citation:
 Keratin-17 Promotes p27KIP1 Nuclear Export and Degradation and Offers Potential Prognostic Utility
 Luisa F. Escobar-Hoyos, Ruchi Shah, Lucia Roa-Peña, Elizabeth A. Vanner,Nilofar Najafian, Anna Banach, Erik
Nielsen, Ramsey Al-Khalil, Ali Akalin,David Talmage, and Kenneth R. Shroyer
 Cancer Res Published OnlineFirst June 24, 2015; doi:10.1158/0008-5472.CAN-15-0293

Melatonin Did Not Improve Fatigue in Cancer Patients
MedicalResearch.com Interview with: Charlotte Lund Rasmussen
Research Unit, Department of Palliative Medicine
Bispebjerg Hospital, Copenhagen, Denmark
findings?
 Response: We see that patients with advanced cancer often suffer from fatigue,
pain, depression, insomnia and other symptoms, which can have a profound impact
on quality of life. Melatonin is a neurohormone and its secretion is closely tied to the
circadian rhythm making it a regulator of the sleep-cycle.
 Studies have shown that cancer patients have lower levels of melatonin than healthy
controls, which may contribute to their fatigue and lowered quality of life.
Furthermore, previous studies have found a possible effect of melatonin in cancer
therapy, and non-clinical trials have shown melatonin to inhibit cell division in tumors.
 To our knowledge, no trials to date have investigated the effects of melatonin on
fatigue. Given the role of melatonin in the sleep cycle, the lowered levels of melatonin
noted among cancer patients, and results from previous studies, we wanted to
investigate melatonin’s effect on fatigue among patients with advanced cancer.

Melatonin Did Not Improve Fatigue in Cancer Patients
MedicalResearch.com Interview with: Charlotte Lund Rasmussen
Research Unit, Department of Palliative Medicine
Bispebjerg Hospital, Copenhagen, Denmark
 The primary objective of our study was to determine whether oral melatonin
administered at night would reduce physical fatigue in patients with advanced cancer
who were being treated in a palliative care facility. The effect of melatonin on other
cancer-related symptoms including mental fatigue, insomnia, pain, emotional
function, loss of appetite, and overall QoL were also investigated.
 In this trial we tested a dose of 20 mg of melatonin taken orally at night.
 However, melatonin did not improve physical fatigue in patients with advanced
cancer. Furthermore, we were unable to identify improvements in any other cancer-
related symptoms.

Telemedicine May Help Patients Adopt Healthy Lifestyle and Manage Chronic Diseases
MedicalResearch.com Interview with: Dr. Rashid Bashshur PhD Director of Telemedicine University of Michigan
Health System
Emeritus Professor of Health Management and Policy
University of Michigan, School of Public Health
findings?
 Dr. Bashshur: The impetus for this research derives from the confluence of several
factors, including the increasing incidence and prevalence of chronic diseases, their
associated morbidity and mortality and their high cost. The search for solutions has
taken center stage in health policy. Patients must be engaged in in managing their
health and health care, and they must assume greater responsibility for adopting and
maintaining a healthy life style to reduce their dependence on the health system and
to help themselves in maintaining an optimal level of health. The telemedicine
intervention promises to address all these issues and concerns, while also providing
ongoing monitoring and guidance for patients who suffer from serious chronic illness.

Health System
The preponderance of the evidence from robust scientific studies points to the beneficial
effects of the telemedicine intervention (through telemonitoring and patient engagement)
in terms of reduction in use of service (including hospital admissions/readmissions, length
of hospital stay, and emergency department visits) as well as improved health
outcomes. The single exception was reported in a study among frail elderly patients with
co-morbidities who did not benefit from the telemedicine intervention.

Health System
 There is an ever-growing and complex body of empirical evidence that attests to the
potential of telemedicine for addressing the triad problems of limited access to care,
uneven distribution of quality across communities, and cost inflation. Research
demonstrates the effectiveness of the telemedicine intervention in addressing all
three problems, especially when patients are engaged in managing their personal
health and healthcare. The enabling technology can be used to promote healthy life
styles, informed decision making, and prudent use of health resources.
 Unintended consequences of delaying mortality for older adults may also increase
the use of resources, especially in the long run, and society must decide on the
ultimate values it chooses to promote.

Health System
report?
 Dr. Bashshur: Clinicians can appreciate the limits of the traditional in-person chronic
care process in managing chronic diseases, as well as their current and potential
role in the management of chronic diseases, and the need for the type of innovation
that is rendered by telemedicine by enabling the provision of appropriate care at the
appropriate time and place instead of relying on the long-standing “revolving
door” arrangement whereby chronically ill patients are scheduled for repeat visits at
fixed arbitrary intervals, and often being forced to use the emergency department for
interim disease exacerbations and problems.
 Patients can learn and appreciate the role of telemedicine in contributing to the
adoption of healthy life styles and compliance with medical regimen, including proper
diet, exercise and smoking cessation (among smokers) as well as medication
compliance, behaviors which enhance their health and wellbeing, and also decrease
their dependence on the health system.

Health System
 Dr. Bashshur: Future research must be concerned with
 (a) methodological rigor (robust research designs, valid measurement, adequate statistical power for sub-group analysis, etc.),
 (b) the fidelity of the intervention, choice of the appropriate settings (in terms of maturity) with the appropriate level of strength and
integrity, including type and range of clinical applications (type and range of services, technological configurations (telephone, video,
cameras, scopes sensors, wearables, implantables… automated and non-automated, wired and mobile, communication mode
(synchronous and asynchronous), manpower mixes (physicians, nurses, therapists managers, as well as organizational structures and
protocols). In other words, in order to ascertain the true effects of telemedicine, the concept (the independent variable) must be
operationalized in explicit terms, preferably in optimal terms as a complex programmatic intervention, in order to assure cause and effect
attribution.
 Citation:
 Telemed J E Health. 2014 Sep;20(9):769-800. doi: 10.1089/tmj.2014.9981. Epub 2014 Jun 26.
 The empirical foundations of telemedicine interventions for chronic disease management.
 Bashshur RL1, Shannon GW, Smith BR, Alverson DC, Antoniotti N, Barsan WG, Bashshur N, Brown EM, Coye MJ, Doarn CR, Ferguson
S, Grigsby J, Krupinski EA, Kvedar JC, Linkous J, Merrell RC, Nesbitt T, Poropatich R, Rheuban KS, Sanders JH, Watson AR, Weinstein
RS, Yellowlees P.

Healthy Diet Not Cure-All For Depression
Dr. Mila Kingsbury PhD
Senior Research Associate at Department of Epidemiology and Community Medicine
University of Ottawa

 Dr. Kingsbury: Eating a healthy diet, including enough fruits and vegetables, is good
for physical health, and some evidence suggests that it may be good for mental
health, too. Specifically, intake of fruits and vegetables has been associated with
lower risk of depression.
 However, there are very few longitudinal studies on this topic. Most studies haven’t
accounted for the effects of other related lifestyle factors such as smoking and
exercise, nor for the fact that the links between lifestyle and mental health are
bidirectional (i.e., depression can also hinder our ability to engage in healthy
behaviours).

 Dr. Kingsbury: While we found an association between fruit and vegetable
consumption and psychological distress and depression two years later, depression
and distress also predicted future fruit and vegetable consumption. Importantly, these
associations became non-significant when we controlled for lifestyle factors like
smoking and exercise.

report?
 Dr. Kingsbury: Although eating a healthy diet, including lots of fruits and vegetables,
certainly has many health benefits, diet may not be a ‘cure-all’ for mental health
problems such as depression and psychological distress. Instead, diet is likely one
component of a healthy lifestyle involving many behaviors which contribute to mental
health.

 Dr. Kingsbury: Our findings highlight the need for randomized control trials to clarify
whether there are causal links between fruit and vegetable consumption and mental
health.
 Citation:
 Associations between fruit and vegetable consumption and depressive symptoms:
evidence from a national Canadian longitudinal survey
 Mila Kingsbury, Gabrielle Dupuis, Felice Jacka, Marie-Hélène Roy-Gagnon,
 Seanna E McMartin, Ian Colman
 J Epidemiol Community Health jech-2015-205858Published Online First: 26 August
2015doi:10.1136/jech-2015-205858

“Happy Meal” Law Would Decrease Fat, Sugar, Salt and Calories in Kids’ Meals
MedicalResearch.com Interview with: Brian D. Elbel, PhD, MPH Associate professor, Departments of Population Health,
Division of Health and Behavior and Medicine, Division of General Internal Medicine
Marie Bragg, PhD Assistant professorDepartment of Population Health
Jonathan Cantor, MS Department of Population Health, Section on Health Choice, Policy and Evaluation NYU Langone
Medical Center
 MedicalResearch: What is the background for this study?
 Response: On July 17th, 2014 the New York City Council proposed the “Healthy Happy Meals” bill in an effort to
improve the nutritional value of fast food restaurant meals marketed to children. The bill states a restaurant cannot
offer an incentive item (i.e. a toy) in combination with the purchase of a meal unless the meal met several
nutritional standards.
 The meals with toys would be required to:
 Be less than 500 hundred calories total
 Be less than 600 milligrams of sodium total
 Have less than 35% of total calories come from fat
 Have less than 10% of total calories come from saturated fat
 Have less than 10% of total calories come from added sugar
 Contain one half cup of fruit or vegetable or one serving of whole-grain products
 This study examined potential reductions in purchased calories, sodium and percentage of calories from fat that
could occur among children if the policy were to go into effect.

Medical Center
 MedicalResearch: What are the main findings?
 Response: Researchers collected receipts for fast food purchases for 422 children
who were accompanied by 358 adults. On average, adults purchased 600 calories for
each child, with 36 percent of those calories coming from fat. One third of the children
in the sample had a children’s meal, with 98% of the purchased children’s
combination meals would be restricted from handing out a toy with the meal if the bill
passed.
 If the bill passed, there would be a 9% reduction in calories purchased for kid’s
meals, the equivalent of 54 calories. Similarly, researchers found that there would be
a 10% (83 mg) reduction in sodium purchased and a 10% reduction in the
percentage of calories from fat purchased for children. This all assumes that children
ordered what they did previously but the meals meet the nutrition criteria.

Medical Center
 MedicalResearch: What should clinicians and patients take away from your
report?
 Response: This study was designed to help address that toys are used in promoting
unhealthy kids meals, and the results show that this policy could improve children’s
diets. The study demonstrates that small dietary improvements can be made with
slight adjustments to children’s combination meals. Clinicians can discuss the role
marketing plays in the purchase of children’s combination meals and encourage
parents to avoid linking rewards like toys with unhealthy foods. Parents can play an
important role by deciding to choose a healthier food item for their child or decide not
to go to the fast food restaurant at all.

Medical Center
 MedicalResearch: What recommendations do you have for future research as a result of this study?
 Response: We suggest researchers evaluate consumer responses to these types of policies. Such policies could
encourage a variety of possible outcomes. First, children may decide to order larger portions from the restaurant’s
adult menu, a result that would lead to excess food consumption. An alternative outcome is that children and
parents may decide to purchase their meal elsewhere (that is either healthier or less healthy than the fast food
restaurant).
 The current policy would be a small change for a large number of children. Although no single policy will eliminate
childhood obesity, this policy could be a step in the right direction. In the future, similar policies should be
considered in other municipalities.
 Citation:
 New York City “Healthy Happy Meals” Bill: Potential Impact on Fast Food Purchases
 Brian Elbel, Tod Mijanovich, Jonathan Cantor, Marie A. Bragg
 American Journal of Preventive Medicine DOI: http://dx.doi.org/10.1016/j.amepre.2015.05.030
 Publication stage: In Press Corrected Proof
 Published online: August 6 2015

Poor Patients Receiving Care Through Ryan White Programs Achieve Better HIV Control
MedicalResearch.com Interview with: Dr. John Weiser MD MPH
Medical epidemiologist
Division of HIV/AIDS Prevention
CDC
findings?
 Dr. Weiser: Ryan White was an Indiana teenager diagnosed with AIDS in the late
1980s. As a result of fear and stigma, he was barred from school and went on to
become a national advocate for HIV education and acceptance. This year marks the
25th anniversary of his death and passage of the Ryan White CARE Act creating The
Ryan White HIV/AIDS Program (RWHAP) which provides funding for healthcare
facilities to deliver needed medical care and support services for hundreds of
thousands of poor, uninsured, and underinsured Americans. While increased access
to Medicaid and private insurance under the Affordable Care Act will provide
coverage for medical care, it might not provide coverage for support services so it is
likely that the RWHAP will continue to play a key role in providing these crucial
services.

CDC
Overall, 34.4 percent of facilities received Ryan White HIV/AIDS Program funding and
72.8 percent of patients received care at RWHAP-funded facilities. Many of the patients
at Ryan White HIV/AIDS Program -funded facilities had multiple social determinants of
poor health, with patients at RWHAP-funded facilities more likely to be ages 18 to 29;
female; black or Hispanic; have less than a high school education; income at or below the
poverty level; and lack health care coverage.

CDC
Despite the greater likelihood of poverty, unstable housing and lack of health care
coverage, nearly 75 percent of patients receiving care at RWHAP-funded facilities
achieved viral suppression. The percentage of ART (antiretroviral therapy) prescribing
was similar for patients at RWHAP-funded compared with non-funded facilities. Patients
at RWHAP-funded facilities were less likely to be virally suppressed. However, individuals
at or below the poverty level and those ages 30 to 39 who received care at a RWHAP-
funded facility compared with those who received care at a non-RWHAP-funded facility
were more likely to achieve viral suppression.

CDC
report?
 Dr. Weiser: Our findings supports the premise that RWHAP-funded facilities, which
provide substantial support services for marginalized persons (e.g., those living at or
below the poverty level), provide better care for poor persons compared with non-
Ryan White HIV/AIDS Program -funded facilities.

CDC
 Dr. Weiser: Among HIV-infected persons in the United States, 70% are not virally
suppressed. Of those, two thirds are not in care. (Vital Signs, 2014) Further research
is needed to explore the association between supportive services funded by the Ryan
White HIV/AIDS Program and linkage to and retention in care.
 Citation:
 Weiser J, Beer L, Frazier EL, et al. Service Delivery and Patient Outcomes in Ryan
White HIV/AIDS Program–Funded and –Nonfunded Health Care Facilities in the
United States. JAMA Intern Med. Published online August 31, 2015.
doi:10.1001/jamainternmed.2015.4095.

Distance From Hospital Linked To Worse 30-Day Cardiac Surgery Outcomes MedicalResearch.com Interview
with: Dr. Ansar Hassan MD PhDz
Department of Cardiac Surgery New Brunswick Heart Centre
Saint John Regional Hospital
Saint John, New Brunswick
findings?
 Dr. Hassan: For years, geographic place of residence and one’s proximity to a
tertiary care center has been identified as a predictor for access to care. Little is
known regarding the effect of geography on patient outcomes. The purpose of this
study was to explore the relationship between geography and in-hospital / 30-day
outcomes among patients undergoing cardiac surgery. What we found was that
despite there being no relationship between geography and in-hospital outcomes,
those who lived further away from hospital clearly had worse 30-day outcomes.

report?
 Dr. Hassan: While patients from a differing geographic places of residence appear to
have similar in-hospital outcomes following cardiac surgery, their clinical courses
following discharge from hospital differ considerably. Clinicians and patients need to
realize that where one lives is tremendously important as it relates to his or her health
and that particular attention needs to be paid to cardiac surgery patients who live
further away from their tertiary care center, especially within the first 30 days following
surgery.

 Dr. Hassan: This is a study that will hopefully generate a lot of conversation around the subject of 30-day
outcomes following cardiac surgery. However, before we instinctively jump to trying to solve the geographic
discrepancies found in this study, we need to know more about why these differences existed in the first
place. Was it that patients from further away experienced more complications following surgery? Was it that they
had impaired access to local health care facilities and that it was this decrease in access that led to worse
outcomes? Was it that they were more likely to be readmitted to their local hospital with complications and or
clinical presentations that would have been managed as an outpatient had they been seen at the hospital where
their surgery was performed? These questions need to be answered before we can jump to the desired step of
proposing solutions.
 Citation:
 Ann Thorac Surg. 2015 Aug 11. pii: S0003-4975(15)00896-6. doi: 10.1016/j.athoracsur.2015.05.058. [Epub ahead
of print]
 Increased Distance From the Tertiary Cardiac Center Is Associated With Worse 30-Day Outcomes After Cardiac
Operations.
 Cote CL1, Singh S1, Yip AM2, Murray J3, MacLeod JB2, Lutchmedial S2, Brown CD2, Forgie R2, Pelletier
MP2, Hassan A4.

Gene Variant May Explain Why Some Children Respond More Aggressively To Stress
MedicalResearch.com Interview with: Beate W. Hygen PhD Student
Department of Psychology
Norwegian University of Science and Technology Social Science
 Response: The study is part of the Trondheim Early Secure Study (TESS) conducted at
the Department of Psychology, Norwegian University of Science and
Technology (NTNU) and NTNU Social Science. The main aim of TESS is to detect risk and
protective factors with regards to children’s mental health and well-being. TESS examines
multiple factors which may play a role in children`s development.
 There is substantial research, based on diathesis-stress theorizing, indicating that some
individuals, including children, are more susceptible to the negative effects of contextual
adversity than are others. However, according to differential susceptibility theory, such
“vulnerable” individuals may also be the ones that benefit the most from positive
environmental conditions. Thus, some individuals are more malleable for “better and for
worse” to environmental exposures. The article Child exposure to serious life events,
COMT, and aggression: Testing differential susceptibility theory was designed to examine if
the COMT polymorphism moderated the effect of early-life adversity on aggressive
behavior. Thus, we sought to competitively evaluate which model of person X environment
interaction best accounted for the anticipated differential effects of life event stress on
children’s aggressive behavior.

 Response: The main findings of this study indicated that COMT, a gene that instructs
the production of the enzyme catechol-O-methyltransferase, which breaks down
dopamine, epinephrine, and norepinephrine, moderated the effect of exposure to
serious life events on teacher-rated aggression at age four (in the absence of
main effects of either COMT or SLEs) in a manner consistent with differential
susceptibility rather than diathesis stress thinking: It was not only the case that
children carrying two Val alleles evinced greater aggression than other children
carrying 1 or 2 Met alleles when they experienced many negative life events, but they
also proved less aggressive than these other children when they experienced no
negative life events. Thus, Val homozygotes were most developmentally plastic,
becoming the most or least aggressive children depending on the quality of their
developmental experiences.

report?
 Response: Children vary, as a function of their genetic make-up in whether adverse
childhood experiences affect their levels of aggression. And those most likely to
become aggressive in the face of adverse life circumstances are the same ones most
likely to benefit from supportive or even just benign ones. This suggests, as
experimental evidence is beginning to indicate, that the therapeutic benefits of
intervention will accrue to some more than others. Indeed, children who are
aggressive due to growing up under conditions of adversity would seem most likely to
become less aggressive when those conditions change, perhaps as a result of
clinical support. Therefore, children with aggressive problems may be the ones that
especially profits from psychosocial interventions aimed at reducing their
aggressiveness.

 Response: More attention should be paid to the notion that those most likely to be
vulnerable to adversity will also benefit the most from supportive conditions.
Experiments should now be conducted to test the derived proposition that Val
homozygotes who are aggressive will change more than other aggressive children–
and for the better–when treated for their problematic behavior.
 Citation:
 Dev Psychol. 2015 Aug;51(8):1098-104. doi: 10.1037/dev0000020. Epub 2015 Jun 8.
 Child exposure to serious life events, COMT, and aggression: Testing differential
susceptibility theory.
 Hygen BW1, Belsky J2, Stenseng F3, Lydersen S4, Guzey IC5, Wichstrøm L1.

Cancer Driver Log Facilitates Precision Medicine, Linking Providers With Genetic Data Bank
MedicalResearch.com Interview with:Sameek Roychowdhury, MD, PhD
Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology
College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center
The Ohio State University

findings?
 Dr. Roychowdhury: Precision cancer medicine is a new paradigm to match patients
to therapies based on the molecular alterations in their cancer. Novel genomic testing
of cancer using next generation sequencing can reveal numerous mutations for each
patient across many genes and types of cancer, and this requires detailed time-
intensive interpretation. Driver mutations can confer a selective growth or survival
advantage to cancer cells, while passenger mutations do not.
 Cancer Driver Log, or CanDL, is meant to aid interpretation of mutations by providing
the latest literature evidence for individual driver mutations, and thereby aiding
pathologists, lab directors, and oncologists in interpreting mutations found in their
patient’s cancer.

report?
 Dr. Roychowdhury: Cancer Driver Log is a freely available resource connecting
driver mutations to the latest literature evidence.
 Researchers and clinicians can also directly contribute to the upkeep of CanDL may
submitting mutations and providing feedback on the website. (candl.osu.edu)

 Dr. Roychowdhury: Efforts to consolidate identification and curation of clinically relevant
mutations in cancer will facilitate implementation of precision cancer medicine for our
patients.
 Citation:
 Cancer Driver Log (CanDL): Catalog of Potentially Actionable Cancer Mutations
 The Journal of Molecular Diagnostics, Volume 17, Issue 5, September 2015, Pages 554-
559
 Senthilkumar Damodaran, Jharna Miya, Esko Kautto, Eliot Zhu, Eric Samorodnitsky,
Jharna Datta, Julie W. Reeser, Sameek

Serious Injuries Rise As Older Age Groups Takes Up Cycling MedicalResearch.com Interview
with: Benjamin N. Breyer MD, MAS, FACS Associate Professor in Residence
Department of Urology University of California, San Francisco
Chief of Urology, San Francisco General Hospital
Director, UCSF Male Genitourinary Reconstruction and Trauma Surgery Fellowship
findings?
 Dr. Breyer: Our group has studied genitourinary-specific injuries associated with
bicycles using a national surveillance injury database called NEISS (National
Electronic Injury Surveillance System), that monitors injuries associated with specific
products. In the current study, we examined trends in all bicycle-related injuries
from 1997 to 2013. We found an increase in bicycle-related injuries over the study
period, even after adjusting for growth in the US population. Even more concerning,
we found the percentage of bicycle-related injuries resulting in admission increased
120%, suggesting the injuries sustained while cycling are becoming more
severe. These trends appear to be driven by a substantial rise in both injuries and
admissions in individuals over 45 years of age, which likely reflects a change in the
demographic of cyclists in the US – multiple studies have shown an increase in the
cycling participation of adults over the age of 45.

Bicycles are no longer children’s toys – they are increasingly being used by adults as a
means of transportation and physical activity. The rise in cycling in adults over the age 45
appears to be driving both the increase in injuries and admissions, suggesting that older
individuals are at increased risk for sustaining severe injury while cycling.

report?
 Dr. Breyer: Bicycle riding provides a fantastic way to get exercise that is low impact;
it is also can be a great way to commute. Previously, bicycle riding has been
associated with reduced mortality and robust general health benefits. We are seeing
more older riders get hurt and we’re seeing more head and torso injuries. I think
clinicians should encourage bicycle riding but also promote helmet and safety gear
usage, also well as safe riding practices.

 Dr. Breyer: As cyclists in the US shift to an older demographic, greater attention is needed
in injury prevention measures through improved infrastructure (e.g. bicyce lanes), personal
protective equipment use (e.g. helmets) as well as improved rider/motorist education.
 More research is needed to study the costs of bicycle injuries. More research is needed
into how we can make bicycle riding more safe, all the way from the bicycle itself, the rider
and on a policy level/infrastructure level.
 Citation:
 Thomas Sanford, MD et al. Bicycle Trauma Injuries and Hospital Admissions in the United
States, 1998-2013. JAMA, September 2015 DOI: 10.1001/jama.2015.8295

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