MedicalResearch.com: Medical Research Exclusive Interviews April 20 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
April 20 2015
For Informational Purposes Only: Not for Specific Medical Advice.

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A Bad Marriage May Lead to High Blood Pressure
MedicalResearch.com Interview with: Kira S. Birditt, Ph.D.
Research Associate Professor
Life Course Development Program The Institute for Social Research
University of Michigan Ann Arbor, MI
• Medical Research: What is the background for this study? What are the main findings?
Dr. Birditt: We know that negative marital quality (e.g., conflict, irritation) has important
implications for physical health but the mechanisms that account for these links are still
unclear. This study explored links between negative marital quality (e.g., criticism, demands),
stress (long term chronic stresses) and blood pressure among older married couples in a
large longitudinal nationally representative sample of couples in the U.S.. We found that
husbands had higher blood pressure when wives reported greater stress and that this link
was even greater when husbands felt more negative about the relationship. In addition,
negative marital quality experienced by only one member of the couple was not associated
with blood pressure but when both members of the couple reported higher negative marital
quality they had higher blood pressure.
• Medical Research: What should clinicians and patients take away from your report?
• Dr. Birditt: When examining a married individual’s cardiovascular health, it is important to
consider both members of the couple to understand what may be negatively influencing an
individual’s cardiovascular health.
Read the rest of the interviews on MedicalResearch.com
Content NOT an endorsement of efficacy and NOT intended as specific medical advice.

A Bad Marriage May Lead to High Blood Pressure
MedicalResearch.com Interview with: Kira S. Birditt, Ph.D.
Research Associate Professor
Life Course Development Program The Institute for Social Research
University of Michigan Ann Arbor, MI
• Medical Research: What recommendations do you have for future research as a result of
this study?
• Dr. Birditt: Future research should explore other health indicators to assess whether there
are similar outcomes when measuring the immune system and the metabolic system, for
example. Future research should also explore the coping strategies couples use when they
experience negativity in their relationships to understand the strategies that may exacerbate
or buffer the effects of negative quality and stress on blood pressure.
• Citation:
• Kira S. Birditt, Nicky J. Newton, James A. Cranford, and Lindsay H. Ryan. Stress and Negative
Relationship Quality among Older Couples: Implications for Blood Pressure. J Gerontol B
Psychol Sci Soc Sci, April 7, 2015 DOI: 10.1093/geronb/gbv023

Sleep Disturbance in Glaucoma Patients Due To Retinal Ganglion Cell Death
MedicalResearch.com Interview with:
Carolina P B Gracitelli, M.D.
Ophthalmology – PhD Candidate/ Research Fellow
University of California San Diego – Hamilton Glaucoma Center
Dr. Gracitelli: Of all the diseases that can lead to blindness, glaucoma is one of the most
important diseases; it affects more than 70 million people worldwide, of whom
approximately 10 % are bilaterally blind. Different studies have reported that the damage
caused by glaucomatous disease lead to retinal ganglion cell (RGC) loss and consequently loss
of intrinsically photosensitive retinal ganglion cells (ipRGCs), which is a subtype of retinal
ganglion cell. This subpopulation of RGC is clearly related with non-image-forming visual
function such as photic synchronization of circadian rhythms and the pupillary light reflex.
However, the true impact of glaucoma on sleep quality, sleep disturbance or circadian
rhythm was until nowadays controversial.
• The main clinical finding of our study was that glaucoma leads to retinal ganglion cell death,
including ipRGC death. These cells are connected to several non-image-forming functions,
including circadian photoentrainment and pupillary reflexes. Therefore, the image-forming
and non-image-forming visual systems are associated with glaucoma. Circadian function has
not been well investigated in clinical daily practice, but it can interfere with the quality of life
of these patients. Concerns about sleep disturbances in glaucoma patients should be
incorporated into clinical evaluations.

• Dr. Gracitelli: Our data support the concept that glaucoma is associated with a loss of ipRGCs
that mediate the pupillary light response, particularly to the sustained component of the blue
flash with a luminance of 250 cd/m2. Additionally, glaucoma patients had significant sleep
disturbances that were inversely correlated with a measure of ipRGC function, the pupillary
light reflex. These results suggest that the loss of ipRGCs in glaucoma may also lead to sleep
disturbances. Both non-visual functions of ipRGCs are correlated, indicating that attention
should be paid to the non-image forming visual functions in glaucoma patients.

this study?
• Dr. Gracitelli: Sleep disorders is a complex system, therefore, some conclusions in this study
should be carefully evaluated. Further studies with larger cohorts could also help to elucidate
the association between the pupillary reflex and the polysomnography parameters. And
longitudinal studies can better explain the associations between sleep disorders and
glaucoma progression.
• In addition, we know that there are several types of ipRGCs and they have specific functions
(pupillary reflex or circadian rhythms), therefore, evaluations would also need to include a
more thorough assessment to understand better the specific role of ipRGCs in sleep
disturbances. However, it is true that these ipRGCs functions are impaired in glaucoma,
affecting the quality of life of these patients.
• Citation:
• Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep
Quality in Patients with Glaucoma
• Gracitelli, Carolina P.B. et al. Ophthalmology Published Online: April 06, 2015
• DOI: http://dx.doi.org/10.1016/j.ophtha.2015.02.030

Reducing Emergency Department Costs By Improving Ambulatory Care
Haichang Xin, PhD
Department of Health Care Organization and policy
School of Public Health University of Alabama at Birmingham
• MedicalResearch: What is the background for this study?
• Dr. Xin: Research suggests that nearly half of all emergency department (ED) visits in the
United States are for nonurgent conditions, leading to billions of dollars in potentially
avoidable spending annually. A well-functioning primary care system has the capacity to
provide timely, adequate, and effective care for patients in order to avoid
nonurgent emergency department use and care costs.
• This study examined how deficiencies in ambulatory care were associated with
nonurgent emergency department care costs nationwide, and to what extent these costs can
be reduced if deficiencies in primary care systems could be improved.

Haichang Xin, PhD
• MedicalResearch: What are the main findings?
• Dr. Xin: Patient perceived poor and intermediate levels of primary care quality had higher
odds of nonurgent emergency department care costs (OR=2.22, p=0.035, and OR=2.05,
p=0.011, respectively) compared to high quality care, with a marginal effect (at means) of
13.0% and 11.5% higher predicted probability of nonurgent ED care costs.
• These ambulatory care quality deficiency related costs amounted up to $229 million for
private plans (95% CI: $100 million, $358 million), $58.5 million for public plans (95% CI:
$33.9 million, $83.1 million), and an overall of $379 million (95% CI: $229 million, $529
million) at the national level.

Haichang Xin, PhD
• MedicalResearch: What should clinicians and patients take away from your report?
• Dr. Xin: These findings highlight the target areas and inform policies on effective strategies in
reducing nonurgent ED care costs. Without improving ambulatory care quality, endeavors
simply aiming to encourage the use of outpatient clinics and community health centers, to
increase primary care supply, or to increase ED cost sharing levels may not be effective in
improving healthcare system efficiency and reducing healthcare costs.
• These ambulatory care quality deficiency related costs amounted up to hundreds of millions
dollars. If deficiencies in primary care systems could be improved, these substantial amounts
of costs can be reduced nationwide.
• MedicalResearch: What recommendations do you have for future research as a result of
this study?
• Dr. Xin: Future studies may consider examining specific deficiency areas in ambulatory care
quality that are associated with nonurgent ED care costs. Future research may also consider
revealing a causal relationship between deficiencies in ambulatory care system and
nonurgent ED care costs.
• Citation:
• Xin, H, Kilgore, ML, Sen, B, Blackburn J. “Can nonurgent emergency department care
costs be reduced? Empirical evidence from a U.S. nationally representative sample”. Journal
of Emergency Medicine. 2015, In Press

Researchers Discover Some Individuals Are Naturally Resistant To TB
Catherine M. Stein, PhD
Associate professor of epidemiology and biostatistics Case Western Reserve
• MedicalResearch: What is the background for this study? What do you hope to learn?
• Dr. Stein: In a 2002 study, we began to clinically characterize people who lived in households
where there were infectious tuberculosis cases. We followed them for a two-year period and
noticed that approximately 9 percent of household members were resistant to
Mycobacterium tuberculosis (MTB) infection, even though they were highly exposed to the
organism. This finding surprised us because the prevailing notion had been that everyone
living in TB-endemic settings or living with someone who has TB would become infected
eventually. After several years of study, we found a substantial number of these people who
do not have any evidence for MTB infection, so we wanted to do studies to learn if we could
figure out why.

• MedicalResearch: Is MTB resistance a new phenomenon? Do MTB resisters react to a
tuberculin purified protein derivative (PPD) or a gold immunoassay but don’t develop
clinical disease?
• Dr. Stein: We don’t have any reason to believe that MTB-infection resistance is a new
phenomenon. It’s just that no one has thought to look for it before. In terms of the PPD or
gold immunoassays, MTB-resisters produce a negative response to both tests. The way gold
immunoassays are done, three tubes are collected. One is a control. Another is a test for
reacting to MTB. Still another is a positive control to make sure immune cells are alive. The
MTB-resisters show a response to that positive control but not to MTB. It’s not that these
patients don’t have an immune response. It’s just that they have no response to MTB, which
means they have no previous exposure to cause their T-cells to make that response.

• MedicalResearch: Are MTB-resisters immune to the newer multi-drug resistant strains of
TB?
• Dr. Stein: Resistance to MTB infection is independent of the drug resistance pattern of the
bacteria. Thus we would expect them to resist multidrug resistant (MDR)-TB as well. There is
no strong evidence that MDR-TB is more aggressive or virulent.

• MedicalResearch: Is MTB-resistance seen in other populations around the world?
• Dr. Stein: No one has looked. We at Case Western Reserve and Makerere University in
Kampala, Uganda, are the first group to characterize this phenotype. We at Case Western
Reserve have collaborators in South Africa who study diamond and coal miners, and
preliminary data suggests MTB-resistance in that group as well. That’s a population with high
MTB and HIV prevalence, and within this population, a group has emerged that is potentially
resistant to MTB infection. I have also been contacted by a group in Indonesia where the
same MTB infection-resistant phenomenon appears to be emerging, and that group is trying
to replicate our study of MTB-resisters. No one has had the same long-term study that we
have conducted of MTB-resisters, but it is likely that MTB-resistance may exist in other
populations in the world. Hopefully, more researchers will engage in this study of MTB
infection-resistance. In other words, we don’t believe this is unique to Uganda.

Melanoma: BRAF or NRAS Mutations Associated With Worse Survival
Nancy E. Thomas, MD, PhD
Department of Dermatology
University of North Carolina
• Dr. Thomas: BRAF and NRAS mutations found in melanomas are important for tumor
initiation and maintenance. There are drugs that target BRAF mutations or the pathway that
are approved for BRAF-mutant metastatic melanoma and help improve survival. However, it
remains unknown whether these mutations in primary melanoma are markers for
melanomas with a worse prognosis.

• Dr. Thomas:
• In a large international population-based study, we found that of primary melanomas, 30%
harbor BRAF mutations, 13% have NRAS mutations and the other 57% do not have these
mutations (wildtype).
• In higher primary tumor stage melanomas, BRAF or NRAS mutations were associated with an
approximately 3-fold increased rate of death from melanoma compared to wildtype
melanoma adjusted for other prognostic factors.
• Primary melanomas with NRAS mutations were less likely to have tumor infiltrating
lymphocytes (TILs) in the tumor microenvironment.

• Dr. Thomas:
• In a large international population-based study, we found that of primary melanomas, 30%
harbor BRAF mutations, 13% have NRAS mutations and the other 57% do not have these
mutations (wildtype).
• In higher primary tumor stage melanomas, BRAF or NRAS mutations were associated with an
approximately 3-fold increased rate of death from melanoma compared to wildtype
melanoma adjusted for other prognostic factors.
• Primary melanomas with NRAS mutations were less likely to have tumor infiltrating
lymphocytes (TILs) in the tumor microenvironment.
• Citation:
• Thomas NE, Edmiston SN, Alexander A, et al. Association Between NRAS and BRAF
Mutational Status and Melanoma-Specific Survival Among Patients With Higher-Risk Primary
Melanoma. JAMA Oncol. Published online April 09, 2015. doi:10.1001/jamaoncol.2015.0493.

Breastfeeding Linked To Modest Reduction In Childhood Obesity
MedicalResearch.com Interview with: Jessica G. Woo PhD
Research Assistant Professor Division of Biostatistics and Epidemiology
Lisa J. Martin PhD Associate Professor Division of Human Genetics
Cincinnati Children’s Hospital Medical Center Cincinnati, OH
• Response: Obesity is a major public health concern. In the past 30 years, more and more
children are being considered obese. Because treatment is challenging, researchers are
looking toward prevention. The health benefits of breastfeeding over infant formula feeding
are well recognized, including evidence that breastfeeding may protect against obesity. But,
how much protection it provides and the reasons for protection are unclear. Thus, the
purpose of this paper was to examine the relationship between breastfeeding and reduced
risk of obesity later in life, with special emphasis on potential mechanisms.
• Response: After reviewing more than 80 studies conducted over a period of 20 years, the
authors showed that breastfeeding is associated with a 10 to 20 percent reduction in obesity
prevalence in childhood. Mechanisms that connect human milk and infant physiology include
maternal obesity, development of a healthy gut environment (microbiome) in the infant, and
the development of taste preference and diet quality. Importantly, each of these mechanisms
can be influenced by biologic and social factors which may directly and indirectly affect the
child’s obesity risk.

• Response: Breastfeeding should be considered the optimal food source for infants for many
reasons, but not as a primary obesity prevention strategy. However, the decision to start
breastfeed is not random. Mothers, who choose to try to breastfeed, may have a social
support network that encourages breastfeeding as well as other healthy lifestyle choices. It is
also important to recognize that continuing to breastfeed is not trivial. External challenges
such as sufficient milk volume and a work environment not supportive of breastfeeding may
derail the efforts of many mothers.
• So, both clinicians and patients need to realize that encouraging breastfeeding among those
not otherwise inclined, without improvement in maternal diet, physical activity and other
healthy lifestyle factors, may have limited impact on childhood obesity. Notably, these
healthy lifestyle improvements may have mutual impact for both mother and baby.

this study?
• Response: Several future research directions were identified. Specifically, additional work is
required on understanding of human milk composition and how it is influence by maternal
factors including obesity and diet.
• Second, how the infant gut develops in response to feeding is incompletely understood and
may serve as a key to prevention.
• Third, observational studies will need to better quantify milk exposure accounting for volume
and quality. Lastly, cross disciplinary research is essential. The relationship between
breastfeeding and childhood obesity is complex and likely the result of many factors.
• Citation:
• Jessica G. Woo, Lisa J. Martin. Does Breastfeeding Protect Against Childhood Obesity? Moving
Beyond Observational Evidence. Current Obesity Reports, 2015;
DOI: 10.1007/s13679-015-0148-9

Genetic Diversity of Pancreatic Cancer May Lead To Therapeutic Targets
Dr. Agnieszka Witkiewicz MD
Associate Professor of Pathology
Harold C. Simmons Comprehensive Cancer Center UT Southwestern
• Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five
year survival rate of approximately 6%. This poor outcome is related to multiple factors,
including the relatively late stage of diagnosis, many patients presenting with unresectable
disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease
and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal
adenocarcinoma have remained unclear in spite of prior sequencing efforts.
• Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal
adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited
for the treatment of disease. Specifically, many cases harbored deregulation in pathways
that are the target for drug development. For example, we identified cases that were driven
by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib. Similarly,
multiple cases harbored defects in DNA repair processes that impart sensitivity to select
chemotherapeutic agents and PARP inhibitors. Common pathway deregulation was observed
in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle
regulatory pathways that are all targets for therapeutic intervention.

Genetic Diversity of Pancreatic Cancer May Lead To Therapeutic Targets
Dr. Agnieszka Witkiewicz MD
Associate Professor of Pathology
Harold C. Simmons Comprehensive Cancer Center UT Southwestern
• Dr. Witkiewicz: The data support the overall concept that knowledge of the genetics
of Pancreatic ductal adenocarcinoma could be important for directing the care of the
individual patient. This is an important advance when progressively more cancer cases are
being referred for genetic analysis. Ongoing research and subsequent clinical trials will be
required to fully leverage these findings into rationally targeted treatments yielding improved
patient survival.
• Citation:
• Agnieszka K. Witkiewicz, Elizabeth A. McMillan, Uthra Balaji, GuemHee Baek, Wan-Chi Lin,
John Mansour, Mehri Mollaee, Kay-Uwe Wagner, Prasad Koduru, Adam Yopp, Michael A.
Choti, Charles J. Yeo, Peter McCue, Michael A. White, Erik S. Knudsen. Whole-exome
sequencing of pancreatic cancer defines genetic diversity and therapeutic targets. Nature
Communications, 2015; 6: 6744 DOI: 10.1038/ncomms7744

1 in 5 Hospitalizations in Cancer Patients May Be Avoidable
Gabriel Brooks, MD
Gastrointestinal Cancer Center
Dana-Farber Cancer Institute
Dr. Brooks: The background for our study is that hospitalizations in patients with cancer are
common, costly, and distressing to patients. Acute hospital care is the single largest
expenditure category in cancer care, accounting for substantially greater costs than even
chemotherapy. However, patients generally wish to avoid hospitalization, and they certainly
want to avoid complications of treatment that can lead to hospitalization. For these reasons,
we sought to identify the extent to which hospitalizations are perceived as potentially
avoidable by clinicians who are directly involved in patient care.
• We interviewed three physicians for each of 103 patients with cancer who experienced a
hospitalization. For 24 patients (23%) two or more of the three physicians agreed that
hospitalization had been potentially avoidable.

Gabriel Brooks, MD
• Dr. Brooks: We wanted to get a sense for how often hospitalizations are potentially
avoidable. This study suggests that 1 in 5 hospitalizations in cancer patients may be
avoidable, and this finding is consistent with other studies that we and other investigators
have published. I hope our study will lead clinicians to examine their outpatient systems of
care, especially care for acute problems, to identify areas for improvement that may help
keep cancer patients out of the hospital.

Gabriel Brooks, MD
this study?
• Dr. Brooks: It will be important for researchers to identify specific clinical approaches that are
effective for preventing complications and managing acute symptoms in the outpatient
setting. This form of health services and implementation research will allow us to identify
approaches for improving ambulatory cancer care in a scalable way that can be exported to
any site where cancer care is delivered.
• Citation:
• Brooks GA, Jacobson JO, Schrag D. Clinician Perspectives on Potentially Avoidable
Hospitalizations in Patients With Cancer. JAMA Oncol. 2015;1(1):109-110.
doi:10.1001/jamaoncol.2014.155.

Costs To Treat Inmates With Hepatitis C Potentially Staggering
Brian Montague, DO MS MPH
Assistant Professor of Medicine and of Health Services, Policy and Practice
Division of Infectious Diseases Brown University / The Miriam Hospital
• Medical Research: What is the background for this study?
Dr. Montague: Hepatitis C is in an important public health problem affecting 4-5 million
persons in the US alone. Given the risk of infection associated with drug use, the prevalence
of hepatitis C in corrections has been significantly higher than in the general population.
• Prior to 2013, the available treatment options were both expensive and of significant toxicity
and limited efficacy. Uptake to these therapies were low. Starting in 2013, new therapeutics
options offering shorter course treatments and efficacies greater than 90% became
available. These therapies offer new possibilities to increase uptake to treatment, however
the cost of the therapies has made rapid scale up of treatment impossible. Given the risk of
serious harms to patients with advanced liver disease if not treated, insurance has begun to
approve these new therapies for patients with more advanced disease.
• Departments of corrections are obliged to provide the same standard of care to persons in
corrections as they would receive in the community. Unlike Medicaid and community
insurance providers, correctional systems worker under a fixed budget. Large increases in
expenditures for treatment of hepatitis C without establishing mechanisms to offset these
costs risks compromising other essential programs and functions in the correctional health
system.

Medical Research: What are the main findings?
Dr. Montague: In a cross-sectional analysis we estimated the burden of hepatitis C within the
department of corrections. At the time of the study, an estimated 836 persons have chronic
hepatitis C. Among these an estimated 119 have advanced liver disease, stage 3 or 4 fibrosis, and
would meet criteria for treatment under most insurance programs. Even a conservative
approach of restricting treatment in corrections to those with stage 3 or 4 fibrosis would incur
costs of over $15 million, which is greater than 6 times the current correctional health budget for
pharmaceuticals and 76% of the overall correctional health budget.

• Dr. Montague: The cost effectiveness of treatment of hepatitis C has been well established
when considering the long term cost savings associated with averting development of
cirrhosis, liver cancer and other complications of end stage liver disease. Achieving those
benefits, however, will require a substantial reconsideration of how the immediate costs of
treatment can be supported in the context of existing systems. This may require rethinking in
some aspects the mandate that all the costs of health care in correctional settings be
supported by the current correctional health budgets.

this study?
• Dr. Montague: Increased attention needs to be given to strategies to improve screening and
evauation of hepatitis C in corrrections, with the goal of identifying those individuals with
advanced fibrosis and assuring that they receive the needed therapies. For those with less
advanced fibrosis for whom release may be expected, strategies to support testing with
linkage to care in the community are needed to assure that those individuals not able to be
treated in corrections are retained care and linked to needed follow-up in the community on
release.
• Citation:
• John T. Nguyen, Josiah D. Rich, Bradley W. Brockmann, Fred Vohr, Anne Spaulding, Brian T.
Montague. A Budget Impact Analysis of Newly Available Hepatitis C Therapeutics and the
Financial Burden on a State Correctional System. Journal of Urban Health, 2015; DOI:
10.1007/s11524-015-9953-4

Antihistamine May Be Useful In Fight Against Hepatitis C
Dr. Jake Liang MD
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
Dr. Liang: Currently existing drugs against HCV, like Sovaldi, are expensive, have some side
effects and are associated with drug resistance. They are not reaching the populations that
are most in need of treatment. We discovered that certain over-the-counter medications
used to treat allergies can block HCV infection in the laboratory and animal model. We still
need to test their benefit in treating people with HCV. The drug blocks the step of HCV
getting into the cells and is different from the current HCV drugs, which block the step of viral
replication.
• Dr. Liang: We don’t know whether this drug works in people with hepatitis C. It still needs to
be tested in human trial.

Antihistamine May Be Useful In Fight Against Hepatitis C
Dr. Jake Liang MD
Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
this study?
• Dr. Liang: Since CCZ has been used widely and have a good safety profile in people, it is
reasonable to consider a trial in people. However we would have to use the currently
accepted dosing for any clinical trial, because chlorcyclizine at high dose may have significant
side effect, such as drowsiness. It is possible that chlorcyclizine in current dosing may not be
active against HCV in people. To further optimize this drug for testing in people, we may have
to modify the drug to make it more active, minimize its antihistamine effect, and improve its
pharmacological properties. This effort will require additional pharmacological research and
development.
• Citation
• Repurposing of the antihistamine chlorcyclizine and related compounds for treatment of
hepatitis C virus infection
Shanshan He1, et al
• Sci Transl Med 8 April 2015:
Vol. 7, Issue 282, p. 282ra49
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3010286

Herpes Zoster Risk May Be Elevated In Psoriasis Patients On Combination Therapy
Arnon D. Cohen, MD, MPH, PhD
Department of Quality Measurements and Research, Chief Physician’s Office, Clalit Health Services, Tel Aviv
• Dr. Cohen: Herpes zoster (HZ), or shingles, is the consequence of reactivation of endogenous
latent varicella zoster virus infection within the sensory ganglia. HZ is a major public health
concern. It is a significant contributor of morbidity, disability, and chronic pain in the form of
post-herpetic neuralgia.
• The use of TNF-α inhibitors in rheumatoid arthritis and similar diseases and the risk
for Herpes zoster has been assessed in several studies. However, the use of TNF-α inhibitors
treatment in patients with psoriasis and the risk for Herpes zoster has been investigated to a
lesser extent. Limited data is available regarding the association between the use of systemic
medications or phototherapy and HZ in patients with psoriasis.
• Dr. Cohen: Among 95,941 Clalit Health Services patients with psoriasis, 4,636 episodes
of Herpes zoster were observed in a follow-up period of 11 years and 7 months.
Monotherapy with biologic or systemic treatment was not associated with an increased risk
for Herpes zoster. In a multivariate analysis, the use of combination treatment with biologic
medications and methotrexate was significantly associated with an increased incidence of
Herpes zoster.

Herpes Zoster Risk May Be Elevated In Psoriasis Patients On Combination Therapy
Arnon D. Cohen, MD, MPH, PhD
Department of Quality Measurements and Research, Chief Physician’s Office, Clalit Health Services, Tel Aviv
• Dr. Cohen: The present study demonstrates an increased risk for Herpes zoster among
patients with psoriasis treated with combination treatment with biologic medications and
methotrexate. Physicians may need to consider offering Herpes zoster preventive vaccine to
patients receiving such treatments, particularly in the setting of additional risk factors for HZ.
this study?
• Dr. Cohen: Future studies should focus on the use of Herpes zoster vaccine in patients with
psoriasis who are treated with systemic or biologic medications.
• Citation:
• Shalom G, Zisman D, Bitterman H, et al. Systemic Therapy for Psoriasis and the Risk of Herpes
Zoster: A 500 000 Person-year Study. JAMA Dermatol. Published online March 22, 2015.
doi:10.1001/jamadermatol.2014.4956.

Depression Less Common In Rural African American Women
Addie Weaver PhD
Research Investigator and LEO Adjunct Lecturer
School of Social Work University of Michigan
Dr. Weaver: The mental health of both African Americans and rural Americans has been
understudied. Though depression is one of the most common, debilitating mental illnesses among
women, very little is known about depression among African American women living in rural areas
of the United States. In fact, much of what we know about rural women’s depression in general is
based on research conducted with community samples, as limited epidemiolgical research includes
large enough samples of both African American respondents and rural respondents to assess
potentially important subgroup differences by urbanicity (e.g., urban, suburban, rural) and race.
Our study used the National Survey of American Life, the first and only nationally representative
survey of African Americans, to examine the interaction of urbanicity and race/ethnicity on Major
Depressive Disorder and mood disorder prevalence among African American and non-Hispanic
white women residing in the South.
• We found that rural residence has a differential effect on depression and mood disorder for African
American women and non-Hispanic white women. Overall, African American women living in rural
areas experienced significantly lower odds of meeting criteria for lifetime and 12-month Major
Depressive Disorder and lifetime and 12-month mood disorder than urban African American
women. Conversely, non-Hispanic white women residing in rural areas had significantly higher odds
of meeting criteria for lifetime and 12-month Major Depressive and lifetime and 12-month mood
disorder when compared to rural African American women, and had significantly higher prevalence
rates of 12-month Major Depressive Disorder and 12-month mood disorder than urban non-
Hispanic white women. All analyses controlled for age, education level, household income, and
marital status, suggesting that the urbanicity differences were not due to resource disparities often
experienced by individuals residing in rural communities.

Addie Weaver PhD
• Dr. Weaver: Results of this study suggest that clinicians should pay more attention to the
rural context and understand that where someone lives may have varied impacts on mental
health for different subgroups. As mental health treatment options are limited in rural
communities, given a lack of providers, as well as accessibility and acceptability related
barriers, many rural patients who choose to seek treatment must travel to more urbanized
areas for care. It is important for both rural and urban-based clinicians to have an awareness
of rural life and assess both protective and risk factors that may be associated with the rural
context. For example, a patient living in a rural area may experience geographic isolation
given the low population density of rural communities that exacerbates depressive
symptoms; however, it is also possible that the dense social networks associated with low
population density may offer greater levels of social support which could be a protective
factor. It may be important for clinicians to obtain information on where patients live, and ask
questions related to the rural context as part of a comprehensive biopsychosocial
assessment.

Addie Weaver PhD
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Dr. Weaver: Though this study did not explore why rural residence may be protective for African
American women’s depression but a risk factor for non-Hispanic white women’s depression, it
provides an important first step toward understanding the cumulative effect of rural residence and
race/ethnicity on women’s depression and mood disorder. Future research could build on this work
by examining aspects of the rural context that may help to explain its differential effect on
depression and mood disorder for African American women and non-Hispanic white women. As
women in rural areas are entering the labor force at faster rates than their urban counterparts, the
potential challenges of juggling multiple roles and responsibilities, including work outside the
home, inside the home, and on the farm, seem important to assess in relation to rural women’s
depression. Additionally, little research has considered strengths of African American women that
may be related to quality of life and emotional well-being, including social support, religiosity and
church involvement, mastery and control, and self-esteem. There is a need for further research
exploring the association between these psychosocial factors and depression among rural African
American women.
• Finally, rural populations are not homogeneous and, for example, rural life in the South, which
reflects our analytic sample, is very different from rural life in rust belt of the Mid-West. It is
important for this research to be replicated across different regions of the country, and to include
respondents of other races and ethnicities.
• Citation:
• Addie Weaver, Joseph A. Himle, Robert Joseph Taylor, Niki N. Matusko, Jamie M. Abelson. Urban vs
Rural Residence and the Prevalence of Depression and Mood Disorder Among African American
Women and Non-Hispanic White Women. JAMA Psychiatry, 2015; DOI:
10.1001/jamapsychiatry.2015.10

Women’s Sex Life After Childbirth Unaffected By Type Of Delivery
Alexandre Faisal-Cury, MD, PhD
Departamento de Medicina Preventiva, Faculdade de Medicina
Universidade de São Paulo São Paulo, Brazil
Response: Childbirth and the postpartum period represent a major life transition and usually
have a substantial impact on the sexual adjustment for both mothers and fathers. Not all
women adapt well to the psychological and biological changes. A variety of reasons have
been implicated for the deterioration of sexual life including marital conflicts, depression and
economic strains. There is conflicting evidence about the role of mode of delivery (MD) on
sexual health outcomes. The purpose of the present study was to evaluate prospectively, up
to 18 months after delivery, the association between mode of delivery and sexual health
outcomes after childbirth, namely later resumption of sexual life, presence of sexual desire,
and self-report of sexual life decline. 831 pregnant women were recruited from primary care
clinics of the public sector in São Paulo, Brazil. Three types of delivery were used:
uncomplicated vaginal delivery (spontaneous vaginal delivery without episiotomy or any kind
of perineal laceration); complicated vaginal delivery (either forceps or normal, with
episiotomy or any kind of perineal laceration) and cesarean delivery.
• Our mains results showed that one hundred and forty one women (21.9%) resumed sexual
life three or more months after delivery. Although 87.1% of women had desire, self-report of
sexual life decline occurred in 21.1% of the cohort. No associations were found between
mode of delivery and sexual health outcomes.

Women’s Sex Life After Childbirth Unaffected By Type Of Delivery
Alexandre Faisal-Cury, MD, PhD
Departamento de Medicina Preventiva, Faculdade de Medicina
Universidade de São Paulo São Paulo, Brazil
• The key message for clinicians and patients is that women’s sexuality after childbirth is not
influenced by the type of delivery. Efforts to improve the treatment of sexual problems after
childbirth should focus beyond the mode of delivery. Despite of the fact, that the mode of
delivery is not associated with sexual health outcomes, sexual dysfunction was quite frequent
among our sample. Decline of sexual life after childbirth may have a negative impact on
several domains of women’s life. Therefore, health professionals should address sexuality
concerns as an essential component in the practice standards during and beyond the
postpartum period.
• Future research about the association between type of delivery and sexuality after childbirth
should assess mechanisms associated more with psychological than organic factors.
• Citation:
• The Relationship Between Mode of Delivery and Sexual Health Outcomes after Childbirth
• The Journal of Sexual Medicine
• Alexandre Faisal-Cury, Paulo Rossi Menezes, Julieta Quayle, Alicia Matijasevich and Simone
Grilo Diniz

Childhood Obesity Common In Both New York and Shanghai
May May Leung Ph.D.
Hunter College School of Urban Public Health,
City University of New York School of Public Health New York, NY
• Dr. Leung: Shanghai and New York City are two urban centers that play a key role in the
global economy. However, both cities are facing elevated rates and inequitable distributions
of childhood obesity. Given the role that obesity plays in the etiology of chronic diseases, this
epidemic calls for interurban learning to better understand some of its diet-related
determinants. In turn, this paper attempts to explore how culture, history and politics have
influenced the rates and distributions of childhood obesity in Shanghai and New York City, to
inform public health officials as to what approaches could be taken to address the epidemic
in ‘world cities’.

May May Leung Ph.D.
• Dr. Leung: Our paper found that Shanghai and New York City face similar, yet unique challenges to
the childhood obesity epidemic. Both cities have combined rates of childhood obesity and
overweight that are higher than their national averages. Childhood obesity first appeared in
Shanghai in 1985 and continues to rise, though the rise is disproportionately greater in high- and
middle-income populations and younger boys, with increasing concern in the growing minority and
migrant population. In New York City, childhood obesity appeared 25 years earlier and is gradually
decreasing, but at the cost of growing inequities; this epidemic is increasingly more prevalent
among low-income populations, especially in black and Hispanic adolescents.
• China’s economic growth has resulted in dietary behaviors consistent with other countries
undergoing a nutrition transition, which include increased consumption of animal products and
edible oils. Chinese children’s diets now resemble that of American children’s in the mid-1990s.
Meanwhile, American youth are now consuming large amounts of carbohydrates and simple sugars.
Changing dietary behaviors in both cities further stem from other influences such as shifts in food
distribution chains, media and marketing of unhealthy foods, and gender and cultural values.
• As the diet-related determinants of childhood obesity are complex and multi-factorial, responses to
address this epidemic should be equally complex, which include multi-sectoral approaches with
action at the individual, family, community, municipal, national and global levels. Shanghai and New
York City have strong municipal governments committed to taking action, but both face challenges
in establishing comprehensive and sustainable programs that reach all sectors of the population.

May May Leung Ph.D.
this study?
• Dr. Leung: This paper highlighted some of the diet-related social and behavioral determinants
of childhood obesity in Shanghai and New York City and identified possible programs and
policies that each city could adopt to address inequalities in childhood obesity prevalence.
Laying this groundwork was fundamental for understanding how cultural, historical and
political differences shaped the distribution of the epidemic in these cities.
• Future research should consider examining the implementation and impact of existing
municipal responses to the childhood obesity epidemic in Shanghai and New York City.
Summarizing existing initiatives will help to better understand how these programs and
policies are shaped and how unique governance structures of Shanghai and New York City
may have influenced their adoption and impact. Such information could help to inform the
development of future program and policy initiatives with increased potential public health
impact.
• Citation:
• Diet-related determinants of childhood obesity in urban settings: a comparison between
Shanghai and New York
• M.M. Leung, H. Fu, A. Agaronov, N. Freudenberg
Public Health Available online 2 April 2015

High Cost-Sharing Policies For Physician Care May Not Benefit Chronically Ill Patients
Haichang Xin, PhD
Department of Health Care Organization and policy School of Public Health
University of Alabama at Birmingham
• Dr. Xin: Since high cost-sharing policies can reduce both needed care and unneeded care use,
it raises the concern whether these policies are a good strategy for controlling costs among
chronically ill patients, especially whether utilization and costs in emergency department (ED)
service and inpatient care will increase in response. Moreover, the costs saved by reduced
physician care may be offset or even exceeded by the increased ED or inpatient care
expenditures, causing a total cost increase for health plans.
• This study was the first to examine whether high cost-sharing policies for physician care are
associated with a differential impact on total care costs between chronically ill individuals and
healthy individuals. Total care includes physician care, ED service and inpatient care.
• Dr. Xin: Chronically ill individuals’ probability of reducing any overall care costs was
significantly less than healthier individuals (β= 2.18, p = 0.04), while the integrated
Difference-in-difference estimator from split results in the two-part model indicated that
going from low cost-sharing to high cost-sharing significantly reduced costs by $12,853.23
more for sick people than for healthy people (95% CI: -$17,582.86, -$8,123.60).

Haichang Xin, PhD
• Dr. Xin: In conclusion, compared with non-chronically ill individuals, chronically ill individuals
reduced their total care costs to a greater extent in response to increased cost-sharing in
physician care. Chronically ill individuals’ greater cost reductions for total care formed a sharp
contrast to their higher demand for medical care compared with that of the general
population. Given this, the greater cost reduction in total care among chronically ill
individuals would not justify high cost-sharing policies for physician care for them, since these
cost savings may have come at the expense of jeopardizing health outcomes by depriving
chronically ill patients of needed care.
• Findings from this study contribute to the insurance benefit design that can control care
utilization and save costs of chronically ill individuals. Health plans need to be cautious of
cost-sharing policies for chronically ill enrollees. A generous benefit design with low cost-
sharing policies in physician care or primary care is recommended for both health plans and
chronically ill individuals, to save costs and protect these enrollees’ health status.
• It may be prudent to have specialized health plans for subpopulations that have chronic
conditions instead of a universal plan with a one size-fits-all benefit structure. The current
study contributes to the necessity and importance of designing insurance policies in terms of
differentiation and specification for the target subpopulation.

Haichang Xin, PhD
this study?
• Dr. Xin: Future research may consider exploring the differential impacts on total costs over
the long term, and trying to reveal a causal relationship of the research question.
• Citation:
• How Do High Cost-Sharing Policies For Physician Care Affect Total Care Costs Among People
With Chronic Disease?
Xin H
• J Ambul Care Manage. 2015 Apr-Jun;38(2):100-8. doi: 10.1097/JAC.0000000000000050.

Nanotechnology May Lead To Breath Test For Gastric Cancer
Professor Hossam Haick Ph.D
Department of Chemical Engineering and Russell Berrie Nanotechnology Institute
Haifa, Israel
Medical Research: What is the background for this study? What are the main findings?
Dr. Haick: Our study is based on the hypothesis that timely detection of premalignant lesions
(PMLs) may provide a tool to decrease either cancer mortality or incidence, thought, currently,
there is no perfect non-invasive tool to screen for gastric cancer (GC) and the related
premalignant lesions. Using 1002 samples collected from 501 volunteers, we show for the first
time that premalignant lesions (PMLs) relevant to (gastric) cancer result in detectable differences
in Volatile Organic Compound (VOC) signatures that can be detected and classified non-invasively
through exhaled breath. We show additionally that these premalignant lesions can be well-
discriminated from various stages of gastric cancer as well as other background stomach diseases.

Haifa, Israel
• Dr. Haick: Our results demonstrate the feasibility of the sensor array for distinguishing
between malignant and non-malignant conditions as well as patients with different stages of
precancerous gastric lesions from gastric cancer by a breath test. Our future vision suggests
the breath test as a follow-up tool for surveillance of high risk patients. Once a patient is
diagnosed with risk-lesions in the stomach by a sensor technology, and this is confirmed by
conventional endoscopy, the breath test could be used for monitoring, to identify those
progressing to cancer or more advanced lesions. Similarly, the test could be used for timely
identification of gastric cancer recurrence following initially successful therapy. The
attractiveness of this test lies in its non-invasiveness, ease of use (therefore high compliance
would be expected), rapid predictiveness, insensitivity to confounding factors and potentially
low cost.

Haifa, Israel
this study?
• Dr. Haick: The results of the present study demonstrates the capacity of the nanoarray
technology to identify the subgroup of patients at high risk for cancer development. Although
high sensitivity is the critical indicator for identifying lesions during screening, higher test
specificity would also be desirable, and additional work will be undertaken to improve the
overall accuracy further.
• Citation:
• Detection of precancerous gastric lesions and gastric cancer through exhaled breath, Gut,
DOI: 10.1136/gutjnl-2014-308536

Could Probiotics Improve Your Mood?
Laura Steenbergen
Leiden University, Institute for Psychological Research, Cognitive Psychology
Leiden, The Netherlands
Response: Food supplements, among which probiotics, are becoming more and more popular. A
lot is known about the effect of probiotics on the physical functioning, but even though there are
some rat studies on the effects of probiotics on mental well-being, not much is known about the
effect in humans. The few studies on humans that are available show beneficial effects on mood
when people experience a bad mood, or psychological distress. Worldwide, millions of people are
suffering from mood disorders like for instance depression, but not everyone receives treatment
for this. Probiotics are safe and easily available, and we therefore wanted to investigate if
probiotics could perhaps be promising in serving as a preventive or adjuvant therapy for mood
disorders of anxiety or depression. We therefore focused on cognitive reactivity to sad mood,
which measures the degree to which people activate dysfunctional thought patterns when
experiencing a sad mood. This measure is known to be predictive of the onset and development
of depression. Compared to subjects who received a 4-week placebo intervention, participants
who received a 4-week multispecies probiotics intervention showed significantly reduced
aggressive and ruminative thoughts. Even if preliminary, these results provide the first evidence
that the intake of probiotics may help reduce negative thoughts associated with sad mood. As
such, our findings shed an interesting new light on the potential of probiotics to serve as adjuvant
or preventive therapy for depression.

Laura Steenbergen
• Response: First of all, we are the first to show a beneficial effect on cognitive reactivity in
healthy participants. More research is definitely needed to this regard, for instance to see if
the beneficial effect can also be obtained in high-risk or patient populations. However, what
can be taken from this study, is that even mood disorders should probably not be treated as
something that only exists in the mind or brain. Given that the gut and the brain are
intimately connected (via what is called the gut-brain axis), and given that probiotics serve
optimal gastrointestinal functioning, a healthy and balanced diet, possibly including
probiotics, might actually help to lower someone’s vulnerability to develop a mood disorder.

Laura Steenbergen
• Medical Research: What recommendations do you have for future research as a result of this
study?
• Response: Whereas the current study investigated the effect of multispecies probiotics on cognitive
reactivity to sad mood in healthy, young volunteers, we think it will be interesting and informative
to study the same possible effect in high-risks population such as elderly people. To add to that, our
study was not designed to test specific biological mechanisms that could underlie possible
beneficial cognitive effects, however, it has for example been proposed by previous studies that
intestinal microbiota increase plasma tryptophan levels, and hereby potentially facilitate serotonin
turnover in the brain. As cognitive reactivity to sad mood has been associated with serotonin
concentrations, with higher scores correlating with lower serotonin levels, it may be that it is this
mechanism that is at play. However, other pathways are plausible as well. For instance, probiotics
have been found to improve the epithelial barrier function and hereby decrease permeability, this
mechanism might also account for the beneficial effects of probiotics on cognitive reactivity.
Follow-up probiotics studies could explore this possibility, for example by using the
lactulose/mannitol ratio in urine to evaluate intestinal permeability, but other possibilities should
be investigated as well.
• Citation:
• A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to
sad mood
Brain, Behavior, and Immunity
• doi:10.1016/j.bbi.2015.04.003 Available online 7 April 2015
• Laura Steenbergen, Roberta Sellaro, Saskia van Hemert, Jos A. Bosch, Lorenza S. Colzato

HPV Vaccine Prevention Of Oropharyngeal Cancer In Boys May Be Cost Effective
Lillian Siu, MD, FRCPC
Princess Margaret Cancer Centre
University Health Network
Toronto
Dr. Siu: Our study is a collaboration between researchers at the Princess Margaret Cancer Centre
and the Canadian Center for Applied Research in Cancer Control. The study involves a statistical
model being applied to a hypothetical population of 192,940 Canadian boys who were 12 years old
in 2012, to determine the cost effectiveness of HPV vaccination for the prevention of
oropharyngeal cancer. On the basis of this model, HPV vaccination for boys aged 12 years appears
to be a cost-effective strategy for the prevention of oropharyngeal cancer in Canada. There are
limitations to our study as it is based on statistical modelling with many assumptions. For instance,
we could not easily address the impact of herd immunity which refers to the indirect protective
effect offered by HPV vaccination in women.
• Based on our statistical model, despite its limitations, the vaccine can potentially save $8 to $28
million CAD for a theoretical group of 192,940 Canadian 12-year old boys in 2012 over their
lifetime. As stated, this is based on a theoretical model and not a randomized study, the results are
relevant especially that HPV-related oropharyngeal cancer is increasing in incidence and HPV is
surpassing smoking as a risk factor for this cancer in many developed countries.
• Currently, the National Advisory Committee on Immunization (NACI) of the Public Health Agency of
Canada recommends HPV vaccination of females 9 through 26 years of age to prevent cervical,
vulvar, vaginal and anal cancers, and for anogenital warts; and of males 9 through 26 years of age to
prevent anal canal cancers and their precursors, and for anogenital warts. However, funding is also
provided for HPV vaccination in young females and not in young males.

Toronto
• Dr. Siu: As with all vaccinations to prevent diseases, the decision to vaccinate or not to
vaccinate should involve an informed discussion between physicians and patients (and
parents/families of young patients in the case of pediatrics) regarding benefits and risks.
Pediatricians are familiar already with this vaccination given its application in young girls. The
data on HPV vaccination in adolescent boys to prevent human papillomavirus (HPV)-related
oropharyngeal cancers (a type of cancer which starts at the back of the throat) are mainly
indirect as randomized clinical trials have not been done. Pediatricians will need to make
recommendation decisions based on their understanding of the available evidence about the
value of HPV vaccination in adolescent boys. Doctors should discuss the benefits and risks of
HPV vaccination of adolescent boys with their patients and families. Currently the vaccine for
adolescent boys is not funded in Canada and it is a personal decision whether patients want
to receive such a vaccine, based on the recommendations by their doctors.

Toronto
this study?
• Dr. Siu: We hope this project will increase awareness from policy makers to further evaluate
the funding support for HPV vaccination in adolescent boys in Canada. It is unlikely that a
randomized clinical trial in this population will be ever done due to the challenges and
feasibility in completing such a study, so indirect evidence such as that provided by statistical
models may represent the main source of information to make such decisions.
• Citation:
• Donna M. Graham, Wanrudee Isaranuwatchai, Steven Habbous, Claire de Oliveira, Geoffrey
Liu, Lillian L. Siu, Jeffrey S. Hoch. A cost-effectiveness analysis of human papillomavirus
vaccination of boys for the prevention of oropharyngeal cancer. Cancer, 2014; DOI:
10.1002/cncr.29111

Salt Capsules May Not Improve Exercise Performance For Endurance Athletes
Edward “Ted” Weiss, Ph.D.
Associate Professor
Department of Nutrition and Dietetics Saint Louis University Saint Louis MO 63104
Dr. Weiss: Public health recommendations are to keep sodium consumption below 2300
mg/day to avoid adverse health effects. However, most people in the US consume over 4000
mg/day. Furthermore, endurance athletes are often advised to add sodium to their diets to
replace the sodium that is lost in sweat and are often lead to believe that the additional
sodium is important for exercise performance. Clearly these recommendations are at odds
with each other.
• In a double-blind placebo-controlled trial, we evaluated the effect of salt capsule
consumption (containing a 1800 mg sodium) on exercise performance and on
thermoregulation during 2 – 2.5 hours of running or cycling. Exercise performance was not
different between the salt and placebo conditions (i.e. it didn’t provide benefit or harm for
performance) nor did any of the markers of thermoregulation differ, suggesting that the salt
didn’t help (or hurt) the body’s ability to cool itself.

Associate Professor
• Dr. Weiss: There is no apparent exercise performance benefit for athletes to use salt
supplements. Modest salt in the diet, within the recommended upper limit of 2300 mg/day
(which would be a reduction for most people), is sufficient for most athletes and avoids the
numerous adverse effects of high salt intake on health outcomes, including hypertension,
coronary artery disease, stroke, heart failure, stomach cancer, osteoporosis, and even
exercise induced asthma/brochospasms.
• One risk that arises from very low sodium consumption during long-duration exercise
(typically >4 or 5 hr), is hyponatremia, which is a life-threatening condition. However,
ironically, this typically arises in people with low fitness and low sweat rates, and is most
commonly caused by extreme over-consumption of water during a marathon or other long-
duration event, to a sufficient extent to cause weight gain. The solution for avoiding this is to
curb the water intake to allow modest water and weight loss during the event (not to exceed
weight loss of >2% of body weight, otherwise heat illness becomes a risk).

Associate Professor
this study?
• Dr. Weiss: Similar trials could be conducted to also evaluate the effects of this salt
supplementation protocol on blood pressure to determine if it increases exercise blood
pressure (this would be undesirable and potentially dangerous).
• Citation:
• Effects of Oral Sodium Supplementation on Indices of Thermoregulation in Trained,
Endurance Athletes
• Elizabeth L. Earhart, Edward P. Weiss Rabia Rahman, Patrick V. Kelly
• Journal of Sports Science and Medicine (2015) 14, 172 – 178

Important Protein Pathway In Brain Plasticity Identified
Erwin G. Van Meir, PhD
Professor, Departments of Neurosurgery and Hematology & Medical Oncology Leader, Winship Cancer Institute Cancer Cell Biology Program
Founding Director, Graduate Program in Cancer Biology Director, Laboratory for Molecular Neuro-Oncology
Emory University School of Medicine Atlanta GA 30322
Dr. Van Meir: In this study we queried the role of the BAI1 protein in normal physiology. To do
this we generated a transgenic mouse, which lacks the expression of the Bai1 gene. The mice had
no obvious anomalies and reproduced according to mendelian rules. Since BAI1 is strongly
expressed in the brain, including in neurons, we wondered whether they might have some
cognitive defect that would only be revealed under specific testing conditions. We had the mice
perform in an experiment that tests their ability to orient themselves in space and memorize the
location of a hidden platform in a water maze. This experiment clearly demonstrated that the
Bai1 deficient mice had deficits in spatial learning and memory. We then further probed the
electrophysiological, anatomical and biochemical basis of this abnormal physiologic behavior and
showed that hippocampal neurons had abnormal synaptic plasticity, reduced thickness of the
post synaptic density and that this was associated with an increased degradation of a key PSD
protein called PSD-95.

• Dr. Van Meir: This is basic research that helps define the role of an abundantly expressed
protein in the brain. However, the type of neurological deficits we uncovered in these mice
are also observed in a number of human diseases. A number of psychiatric and neurological
conditions, including schizophrenia and autism display dysregulation of dendritic spines and
synaptic plasticity. Thus the BAI1 pathway represents a novel target for therapeutics in the
treatment of such disorders. The good news was that we were able to restore the abnormal
electrophysiological response in the hippocampal neurons of the mice through viral gene
therapy. This means that a defect occurring during development can still be corrected later in
life providing hope for patients that such conditions are not irreversible, and that therapeutic
strategies will become possible in the future.

this study?
• Dr. Van Meir: Our study is a milestone in our understanding of the function of BAI1 in the
brain, especially in the hippocampus. Further studies will have to examine whether the
protein plays important roles in other parts of the brain. Also, a lot is still to be learned about
the molecular signals emanating from the BAI1 receptor, what ligands bind to it and what
molecular partners are involved in the transmitting the downstream molecular signaling.
• Citation:
Dan Zhu, Chenchen Li, Andrew M. Swanson, Rosa M. Villalba, Jidong Guo, Zhaobin Zhang,
Shannon Matheny, Tatsuro Murakami, Jason R. Stephenson, Sarah Daniel, Masaki Fukata,
Randy A. Hall, Jeffrey J. Olson, Gretchen N. Neigh, Yoland Smith, Donald G. Rainnie, Erwin G.
Van Meir. BAI1 regulates spatial learning and synaptic plasticity in the hippocampus. Journal
of Clinical Investigation, 2015; DOI: 10.1172/JCI74603

Divorce Raises Risk of Heart Attack, Especially For Women
MedicalResearch.com Interview with: Matthew E. Dupre, PhD
Associate Professor of Medicine
Department of Community and Family Medicine Department of Sociology
Duke Clinical Research Institute
• MedicalResearch: What is the background for this study? What are the main findings?
• Dr. Dupre: The negative health consequences of divorce have been known for some
time. However, we showed that lifetime exposure to divorce can have a lasting impact on
ones’ cardiovascular health, particularly in women. Results from our study showed that risks
for acute myocardial infarction (AMI) were significantly higher in women who had one
divorce, two or more divorces, and among the remarried compared with continuously
married women after adjusting for multiple risk factors. Risks for AMI were elevated only in
men with a history of two or more divorces relative to continuously married men. We were
especially surprised to find that women who remarried had risks for AMI that were nearly
equivalent to that of divorced women. Men who remarried had no significant risk for acute
myocardial infarction.
• The results of this study provide strong evidence that cumulative exposure to divorce
increases the risk of acute myocardial infarction in older adults. Also somewhat unexpected
was that the associations remained largely unchanged after accounting for a variety
socioeconomic, psychosocial, behavioral, and physiological factors. However, we lacked
information on several factors that we suspect may have contributed to the risks related to
divorce – such as elevated stress, anxiety, and the loss of social support; as well as possible
changes is medication adherence or other prophylactic behaviors.

• Dr. Dupre: Although marital loss is not a modifiable risk factor or amenable to medical
intervention, increased knowledge about the risks associated with divorce can assist in
clinical decision-making and improve quality of care. For example, divorced women—
particularly those who experience multiple divorces—may benefit from additional screening
and/or treatment for depression or other symptoms of distress. A greater recognition of
acute and chronic social stressors such as divorce will help physicians identify and treat adults
at potentially high risk of AMI, as well as provide patients a new, or heightened, awareness of
how the social world can get under our skin and damage our heart.

this study?
• Dr. Dupre: More research is needed to better understand the mechanisms at play. A
particularly important avenue of future research should investigate direct measures of
physiological stress and possible changes in preventative health behaviors and the
maintenance of existing conditions that increase risks for heart attack, such as hypertension
and diabetes.
• Citation:
Association Between Divorce and Risks for Acute Myocardial Infarction
• Matthew E. Dupre, PhD; Linda K. George, PhD; Guangya Liu, PhD; Eric D. Peterson, MD, MPH
• Circ Cardiovasc Qual Outcomes. 2015;8:00-00.
DOI: 10.1161/CIRCOUTCOMES.114.001291

Patients May Still Be Getting Unnecessary Pre-Cataract Surgery Testing
Catherine L. Chen M.D., M.P.H.
UCSF Dept of Anesthesia
Dr. Chen: Cataract surgery is a very common and safe surgery that most older adults have in
their 70’s or 80’s. It usually happens as a same-day surgery and most patients only need eye
drops to numb the eye with little or no intravenous sedation for a procedure that on average
is only 18 minutes long. Given their age, these patients typically have other concurrent
medical problems, so even though multiple research studies and professional societies
have concluded that routine preoperative testing is not necessary before cataract surgery, we
found that this testing still frequently occurs in these patients. More than half of the patients
in our study had at least one preoperative test performed in the month before their surgery.
• We hypothesized prior to undertaking this study that the older and sicker patients were the
ones who were most likely to get preoperative testing. Instead, what we found was that the
most important factor that determined whether or not a patient got tested was the
ophthalmologist who operated on the patient. This is an important finding because it shows
that most patients are not getting extra testing, but the few that do are getting
testing because that’s the way their ophthalmologist typically prepares his patients for
surgery. Most of the time, this testing is not needed and will not affect how well the patient
does during and after surgery.

• Dr. Chen: Clinicians should consider not ordering any additional tests when their patients are
scheduled for cataract surgery as long as the patient is in their normal state of health.
Obviously, if the patient has any new symptoms during their preoperative office visit,
physicians should order the appropriate tests to evaluate and manage that condition.
Patients scheduled for cataract surgery should also ask their doctors whether they really
need to have the testing performed for medical reasons other than the fact that they are
having surgery.

this study?
• Dr. Chen: Although we already know that routine preoperative tests do not change outcomes
from cataract surgery, we do not have definitive data for preoperative office visits to a
physician other than the ophthalmologist performing the surgery. It would be interesting to
see whether these additional preoperative office visits are still necessary before cataract
surgery. If the office visits also do not affect how well a patient does during and after the
actual surgery, then this is an additional area where we can safely cut costs without
compromising on healthcare quality.
• Citation:
• Preoperative Medical Testing in Medicare Patients Undergoing Cataract Surgery
• Catherine L. Chen, M.D., M.P.H., Grace A. Lin, M.D., M.A.S., Naomi S. Bardach, M.D., M.A.S.,
Theodore H. Clay, M.S., W. John Boscardin, Ph.D., Adrian W. Gelb, M.B., Ch.B., Mervyn Maze,
M.B., Ch.B., Michael A. Gropper, M.D., Ph.D., and R. Adams Dudley, M.D., M.B.A.
• N Engl J Med 2015; 372:1530-1538
April 16, 2015
DOI: 10.1056/NEJMsa141084

Which Pancreatic Cysts Carry Malignant Potential?
Michael B. Wallace, M.D., MPH
Mayo Clinic
Jacksonville, FL 3222
Medical Research: What is the background for this study?
Dr. Wallace: Since its first consideration as an independent entity in 1996,1 intraductal papillary
mucinous neoplasms (IPMN) of the pancreas have been diagnosed with increasing frequency.
Detection and resection of IPMN offer a unique opportunity to cure and prevent adenocarcinoma
of the pancreas, an otherwise highly lethal disease. The main clinical concern related
to intraductal papillary mucinous neoplasms is its wide-ranging potential for malignancy from
low-risk indolent lesions to those with high incidence of malignant degeneration. It is well-
established that this malignant progression varies based on the morphological subtypes. The
current methods of predicting malignant potential are limited to clinical, morphological, and cyst
fluid cytology and biomarker data.

Mayo Clinic
• Medical Research: What are the main findings?
• Dr. Wallace: Of 1126 patients, 84 were diagnosed with invasive carcinoma/high-grade
dysplasia and were compared to the rest of the cohort. Multivariate logistic analysis showed
no statistically significant association between cancer/high-grade dysplasia and gender, age
or alcohol consumption. Smoking history and body mass index was significantly related with
cancer/ high-grade dysplasia. Jaundice and steatorrhea were also associated with cancer/
high-grade dysplasia; however, weight loss was not. Univariate analysis showed no
association between malignancy and the cyst number/location, although a strong association
was shown for cyst size. The presence/size of nodules, and main duct involvement were
strongly related with malignancy.
• Dr. Wallace: Small cystic lesions of the pancreas are common and most will not progress to
cancer. A subset of these may carry higher risk and should be monitored closely or resected.
This is include large (> 3-4cm) cysts, those with mural nodules, and those associated with
dilations of the main pancreatic duct. Symptoms which suggest a higher risk lesion include
jaundice, and steatorrhea (fatty/oily stools). Smoking and obesity are also modifiable risk
factors.

Mayo Clinic
this study?
• Dr. Wallace: Despite these important clinical predictors, we still need more accurate
methods. Currently the focus is on genomic profiling of cyst tissue obtained by fine needle
biopsy and whole exome sequencing. Minimally invasive (laparoscopic) and even endoscopic
ablation techniques are increasingly available and may offer lower risk options for therapy.
• Citation:
• Risk factors for malignant progression of intraductal papillary mucinous neoplasms
• Maria Moris, Massimo Raimondo, Timothy A. Woodward, Verna Skinner, Paolo G.
Arcidiacono, Maria C. Petrone, Claudio De Angelis, Selene Manfrè, Pietro Fusaroli, Michael B.
Wallace
Received: January 7, 2015; Accepted: March 9, 2015; Published Online: April 10, 201

Acetaminophen May Reduce Both Pain and Emotional Response
Geoff Durso PhD Candidate
Department of Psychology
The Ohio State University
Response: Recent research has shown that acetaminophen blunts negative emotions beyond
those arising from physical pain (e.g., social rejection). We hypothesized that this was the
case because acetaminophen was having a broader effect on individuals’ evaluative and
emotional processing, given past psychological theory (e.g., differential susceptibility,
personality differences in emotionality, etc) and related neurological evidence
(acetaminophen affects serotonin neurotransmission in the brain, reduces inflammatory
signaling in the brain, and decreases activation in the brain areas responsible for emotion, for
instance–any one or combination of these effects could be responsible for the psychological
outcomes that we observe on individuals’ blunted negative and positive evaluations).
• So we conducted two double-blind studies (neither participants nor experiments were aware
of participants’ assignment to condition). What we found was that participants taking an
acute dose of acetaminophen (compared to those taking an inert placebo control) reported
diminished negative evaluations of displeasing stimuli (photographs of starving children,
wartorn city blocks, disgusting toilets) as well as diminished positive evaluations of pleasing
stimuli (photographs of children playing with kittens, a large pile of money, a couple in bed
together). Participants taking acetaminophen also reported experiencing diminished
emotional responses to the photographs overall. These findings supported our predictions
that acetaminophen works to reduce pain in part because it has a broader blunting effect on
individuals’ evaluations and emotional experience.

Acetaminophen May Reduce Both Pain and Emotional Response
Geoff Durso PhD Candidate
Department of Psychology
The Ohio State University
• Response: With specific regards to acetaminophen, our findings suggest that the drug may
work to relieve pain by blunting individuals’ overall evaluations and emotional responses to
both negative and positive influences. More broadly, our findings suggest that past work
which has focused on individuals’ vulnerability to pain and other negative emotional
experiences represents only half the story. In other words, instead of thinking about how
vulnerability to pain and other negatives can be “relieved” by some factor, it may in some
cases be more accurate to think about how individuals’ sensitivity to emotionally relevant
experiences is more or less blunted.
• In terms of health care, we are neither clinicians nor medical doctors, so we cannot make any
recommendations beyond what a medical professional would suggest. If acetaminophen
helps with your pain, then you should continue taking it in whatever capacity that is
recommended by your physician.

MedicalResearch.com: Medical Research Exclusive Interviews April 20 2015

MedicalResearch.com: Medical Research Exclusive Interviews April 20 2015

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MedicalResearch.com: Medical Research Exclusive Interviews April 20 2015