Author Interviews, JAMA, Mental Health Research, Pediatrics / 13.11.2015
Risk of Suicide Doubled In Children Who Lose Parent
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Dr. Gulden[/caption]
MedicalResearch.com Interview with:
Dr. Mai-Britt Guldin PhD
Department of Public Health
Aarhus University
Medical Research: What is the background for this study?
Dr. Guldin: The background for this study is that death of a parent in childhood is experienced by 3-4% of children in Western societies, and we know such a loss is one of the most stressful and potentially harmful events in childhood. Therefore, we aimed to investigate how parental death may influence the long-term risk of suicide and how this risk differes by cause of parental death, age at loss, sex of child, socioeconomic factors and parental history of psychiatric illness.The sample size in this study is unparalleled by other studies on risk of suicide.
Medical Research: What are the main findings?
Dr. Guldin: The main findings were that in a population of 7.302,033 (in three Scandinavian countries), we identified 189,094 persons who lost a parent before the age of 18. Of these bereaved persons, 265 died from suicide. Compared to a control group of persons matched by age and sex, but who did not lose a parent before the age of 18, suicide was twice as common in the bereaved cohort (IRR = 2.02; 95% CI, 1.67-2.44). The risk remained high for at least 25 years of follow-up. The risk was particularly high for children who lost a parent due to suicide, but was also high for children who lost a parent due to other causes. The risk tended to be particularly high for boys who lost a mother and children losing a parent before the age of six.
Dr. Gulden[/caption]
MedicalResearch.com Interview with:
Dr. Mai-Britt Guldin PhD
Department of Public Health
Aarhus University
Medical Research: What is the background for this study?
Dr. Guldin: The background for this study is that death of a parent in childhood is experienced by 3-4% of children in Western societies, and we know such a loss is one of the most stressful and potentially harmful events in childhood. Therefore, we aimed to investigate how parental death may influence the long-term risk of suicide and how this risk differes by cause of parental death, age at loss, sex of child, socioeconomic factors and parental history of psychiatric illness.The sample size in this study is unparalleled by other studies on risk of suicide.
Medical Research: What are the main findings?
Dr. Guldin: The main findings were that in a population of 7.302,033 (in three Scandinavian countries), we identified 189,094 persons who lost a parent before the age of 18. Of these bereaved persons, 265 died from suicide. Compared to a control group of persons matched by age and sex, but who did not lose a parent before the age of 18, suicide was twice as common in the bereaved cohort (IRR = 2.02; 95% CI, 1.67-2.44). The risk remained high for at least 25 years of follow-up. The risk was particularly high for children who lost a parent due to suicide, but was also high for children who lost a parent due to other causes. The risk tended to be particularly high for boys who lost a mother and children losing a parent before the age of six.
Dr. Braun[/caption]
MedicalResearch.com Interview with:
Joseph M. Braun PhD
Assistant Professor
Department of Epidemiology in the Program in Public Health
Brown University
Medical Research: What is the background for this study?
Dr. Braun: Perfluoroalkyl substances are a class of chemicals used to produce stain/water repellent textiles, fire fighting foams, and non-stick coatings. Virtually all people in the US have measurable levels of several different perfluoroalkyl substances in their blood. There is concern that early life exposure to these chemicals can increase the risk of obesity by reducing fetal growth or promoting adipogenesis.
What are the main findings?
Dr. Braun: Pregnant women in our study had perfluorooctanoic acid (PFOA) concentrations in their blood that were over 2-fold higher than pregnant women in the United States (median: 5.3 vs. 2.3 ng/mL) during the same time period (2003-2006).
Children born to women with higher serum PFOA concentrations during pregnancy had a higher body mass index, greater waist circumference, and more body fat at 8 years of age compared to children born to women with lower serum PFOA concentrations
Dr. Wopereis[/caption]
MedicalResearch.com Interview with:
Suzan Wopereis, Ph.D.
TNO, Microbiology and Systems Biology Group
Zeist, The Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. Wopereis: For the first time we could demonstrate the very subtle start of negative health effects caused by a high calorie snack diet in healthy men. We already knew about the negative consequences of such diets from so called epidemiologic studies. In such studies, scientists compare large populations (thousands of people) to better understand disease development. For example, by comparing obese populations to a lean population, scientists could define various steps in the disease development related to obesity, like high cholesterol, onset of inflammation, high blood pressure, high glucose, etc. Yet, the early deviations from health were difficult to study because human metabolism (the way we digest and metabolize our meals from a biochemical viewpoint) is very flexible and able to efficiently deal with all kinds of daily stressors, such as a meal or intensive exercise. So, at TNO we decided to exploit this flexibility by giving our healthy volunteers a ‘challenge test’, in the form of a high-fat milkshake. Next, we studied how multiple aspects of their metabolism react to such a challenge test. We showed that a snack diet for 4 weeks reduced many aspects of flexibility of our healthy men, thus indicating very early changes in health. Both the high-fat challenge test and the integral study of many different outcomes form a novel approach of what “healthy” really means.
In the study we used two groups of male volunteers. One group of 10 healthy male volunteers and one group of 9 male volunteers with Metabolic Syndrome, who had a combination of 2 or more risk factors that raises your risk for heart disease and other health problems (unhealthy cholesterol levels, high blood pressure, high blood sugar, high blood lipids, and abdominal fat). In other words, subjects with Metabolic Syndrome have a suboptimal health condition. Both groups received a high-fat milk-shake, and before and up to 8 hours after consumption of this metabolic challenge-test, blood samples were taken. In these blood samples, 61 different biomarkers were measured, such as cholesterol and blood sugar. These 61 biomarkers were used for a thorough health assessment of these 2 groups in response to the challenge test. We noted that biochemical processes related to sugar metabolism, fat metabolism and inflammation function abnormal in subjects with Metabolic Syndrome. The next step was to provide the 10 healthy male volunteers with a snack diet for 4 weeks. On top of their normal diet they had to consume an additional 1300 kcal per day, in the form of sweets and savory products such as candy bars, tarts, peanuts, and crisps. After these 4 weeks the response of the same 61 biomarkers to the challenge test was evaluated. Here, we observed that signaling molecules such as hormones regulating the control of sugar and fat metabolism and inflammation were changed, resembling the very subtle start of negative health effects. Without the use of the challenge test, we would not have been able to observe that even this short period of overfeeding induces changes in the metabolism of healthy people that resemble what happens in people with metabolic syndrome.
Dr. Bastian[/caption]
MedicalResearch.com Interview with:
Boris C. Bastian, MD, PhD
Professor of Dermatology and Pathology
Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research
University of California, San Francisco
Medical Research: What is the background for this study? What are the main findings?
Dr. Bastian: The cost of DNA sequencing has dropped substantially since the initial sequencing of the human genome in 2001. As a result, the most common cancer subtypes have now been sequenced, revealing the pathogenic mutations that drive them. A typical cancer is driven by 5-10 mutations, but we still do not understand the order in which these mutations occur for most cancers.
Determining the order in which mutations occur is challenging for cancers that are detected at a late stage. Melanomas, however, lend themselves to this type of analysis because they are pigmented and found on the surface of the skin, allowing them to be identified early. Sometimes, melanomas are even found adjacent to their remnant precursor neoplasms, such as benign nevi (also known as common moles). We performed detailed genetic analyses of 37 cases of melanomas that were adjacent to their intact precursor neoplasms. We microdissected and sequenced the surrounding uninvolved normal tissue, the precursor neoplasm, and the descendent neoplasm. By comparing the genetic abnormalities in each of the microdissected areas, we were able to decipher the order of genetic alterations for each case.
Our work reveals the stereotypic pattern of mutations as they occur in melanoma. Mutations in the MAPK pathway, usually affecting BRAF or NRAS, occur earliest, followed by TERT promoter mutations, then CDKN2Aalterations, and finally TP53 and PTEN alterations. Benign nevi typically harbor a single pathogenic alteration, whereas fully evolved melanomas harbor three or more pathogenic alterations. We also identified an intermediate stage of neoplasia with some but not all of the pathogenic mutations required for fully evolved melanoma. There has been a longstanding debate whether morphologically intermediate lesions, such as dysplastic nevi, truly constitute biological intermediates or whether they simply represent a gray zone of histopathological assessment. Our data indicates that these neoplasms are genuine biological entities. Finally, we observe evidence of UV-radiation-induced DNA damage at all stages of pathogenesis, implicating UV radiation in both the initiation and progression of melanoma.

Dr. Garcia[/caption]
MedicalResearch.com Interview with:
Audry H. Garcia PhD
Scientist Department of Epidemiology
Erasmus MC, University Medical Center Rotterdam
Rotterdam, The Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. Garcia: Mild and chronic metabolic acidosis as a result of a diet rich in acid-forming nutrients, such as cheese, fish, meat and grain products, may interfere with optimal bone mineralization and indirectly increase the risk of osteoporosis later in life. Previous observational studies in adults have reported inverse associations between dietary acid load and bone mass. However, the evidence in younger populations is scarce; only a few studies have been performed in healthy children and adolescents with inconsistent results, and not much is known on the effects of dietary acid load on bone mass in younger children or in children with a non-European background.
In a prospective multiethnic population-based cohort study of 2,850 children from the city of Rotterdam, the Netherlands, we found that dietary acid load estimated as dietary potential renal acid load (dPRAL), and as protein intake to potassium intake ratio (Pro:K) at 1 year of age, was not consistently associated with childhood bone health. Furthermore, associations did not differ by sex, ethnicity, weight status, or vitamin D supplementation.

Dr. Lubitz[/caption]
MedicalResearch.com Interview with:
Carrie C. Lubitz, MD, MPH
Assistant Professor of Surgery, Harvard Medical School
Senior Scientist, Institute for Technology Assessment
Attending Surgeon, Mass General/North Shore Center for Outpatient Care
Danvers, Massachusetts
Medical Research: What is the background for this study? What are the main findings?
Dr. Lubitz: Given reported estimates of resistant hypertension and the proportion of resistant hypertensive patients with primary hyperaldosteronism (PA) - the most common form of secondary hypertension caused by a nodule or hyperplasia of the adrenal glands – we estimate over a million Americans have undiagnosed PA. Furthermore, it has been shown that patients with PA with the same blood pressure as comparable patients with primary hypertension have worse outcomes.
In our study, we found that identifying and appropriately treating patients with PA can improve long-term outcomes in patients in a large number of patients who have resistant hypertension.
Dr. Shah[/caption]
MedicalResearch.com Interview with:
Dr. Jatin J. Shah, MD
Associate Professor, Department of Lymphoma/Myeloma
Assistant Professor, Lymphoma/Myeloma
Division of Cancer Medicine
The University of Texas, MD Anderson Cancer Center
Houston, TX
Medical Research: What is the background for this study? What are the main findings?
Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells.
The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma.
Prof. Rogers[/caption]
MedicalResearch.com Interview with:
Prof. Peter J. Rogers PhD
School of Experimental Psychology
University of Bristol, Bristol, UK
Medical Research: What is the background for this study?
Prof. Rogers: In recent years low-calorie sweeteners have been in the headlines because of concern that they may undermine rather than help with healthy weight management. That concern is based on selective reporting of studies and outright speculation. Our aim was to review the totality of evidence on this subject, which included results from human and animal (mouse and rat) studies.
Medical Research: What are the main findings?
Prof. Rogers: We found that randomised, controlled intervention trials in humans showed consistently that low-calorie sweeteners versus sugar consumption reduced energy intake and body weight, with no effect or even reduced body weight compared with consumption of water. These types of studies provide the strongest form of evidence – superior to animal and observational studies. In the animal studies, exposure to
Dr. Vonberg[/caption]
MedicalResearch.com Interview with:
Frederick W. Vonberg, MA, MBBS
Research Fellow in Neurocritical Care
Boston Children's Hospital and Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Response: An association between schizophrenia and epilepsy has long been suspected, ever since people noticed similarities in some aspects of the presentation of the two conditions, and in their epidemiology. For example, people with epilepsy are thought to be more at risk of developing schizophrenia. Furthermore, a psychosis resembling schizophrenia can characterize some forms of
Dr. Bellamine[/caption]
MedicalResearch.com Interview with:
Aouatef Bellamine,
Dr. Lei Xu[/caption]
MedicalResearch.com Interview with:
Lei Xu, MD, PhD
Steele Laboratory of Tumor Biology
Radiation Oncology Department
Massachusetts General Hospital
Medical Research: What is the background for this study?
Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing.
Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves.
Dr. Thakar[/caption]
MedicalResearch.com Interview with:
Charuhas Thakar, MD
Director, Division of Nephrology and Hypertension Professor of Medicine
University of Cincinnati
Medical Research: What is the background for this study? What are the main findings?
"Diabetes is the major contributor to the growing burden of end-stage renal disease,” says Charuhas Thakar, MD, professor and director of the Division of Nephrology and Hypertension at the UC College of Medicine.
"Acute kidney injury is a common problem among diabetic patients who require admissions to hospitals. Approximately one-third of patients who develop AKI also have diabetes mellitus.”
Dr. Thakar along with a team of researchers have looked at a cohort of about 3,700 patients with Type 2 diabetes longitudinally followed for a five-year period to determine AKI’s impact.
AKI is a rapid loss of kidney function, which is common in hospitalized patients.
It has many causes that include low blood volume, exposure to substances or interventions harmful to the kidney and
obstruction of the urinary tract.
MedicalResearch.com Interview with:
Dr. Giuseppe Andò
University of Messina, Messina, Italy
Medical Research: What is the background for this study?
Dr. Andò: Patients’ preference for radial access for coronary angiography and percutaneous intervention is paralleled by an almost complete abolition of access-site bleeding. Given the deleterious impact of any clinically relevant bleeding event on short- and long-term outcomes, the use of radial access should translate into a reduction in net adverse events, especially in patients with high risk of bleeding such as those with an acute coronary syndrome. Nonetheless, studies conducted over the past decade by pioneers of
MedicalResearch.com Interview with:
Dr. Wanpen Vongpatanasin MD
Program Director, Hypertension Fellowship Program
Professor of Internal Medicine
Director of the University of Texas Southwestern Hypertension Program
Medical Research: What is the background for this study? What are the main findings?
Dr. Vongpatanasin: Home blood pressure measurement may reveal very different number when compared to clinic blood pressure in hypertensive patients. This difference can manifest as white coat hypertension (White Coat Hypertension; elevated office blood pressure with normal ambulatory or home blood pressure), or masked hypertension (MH; elevated ambulatory or home BP with normal office blood pressure). Although numerous epidemiological studies from Europe and Asia have shown increased cardiovascular risks associated with White Coat Hypertension and masked hypertension, previous studies have not addressed cardiovascular outcomes associated with White Coat Hypertension and masked hypertension in the general population in the United States.
We found that participants in the Dallas Heart Study, a multiethnic populational-based study in the Dallas County, both White Coat Hypertension and MH are associated with increased aortic stiffness and markers of kidney damage when compared to the group with normal blood pressure both at home and in the clinic. Furthermore, both white coat hypertension and masked hypertension are associated with increased risk of cardiovascular events, including coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death over a median follow-up period of 9 years.
Dr. Nagler[/caption]
MedicalResearch.com Interview with:
Arielle Nagler MD
Instructor, Department of Ronald O. Perelman Department of Dermatology
NYU Langone Medical Center
Medical Research: What are some of the best ways to keep our skin healthy?
Dr. Nagler: Sun protection is the single, most important step you can take to keep your skin healthy. Sun protection can help to prevent many of the signs of aging including wrinkles, changes in skin texture, and uneven pigmentation. Also sun protection has been shown to prevent certain types of skin cancer, which may save you from the distress and scarring of treatment. While we should all be careful in the sun, sun protection doesn’t mean that you have to avoid all outdoor activities and deprive yourself of outdoor fun. If you have any issues with your skin, or want more information, you might want to look into someone like this
Dr. Manning[/caption]
MedicalResearch.com Interview with:
Shannon D. Manning, Ph.D., M.P.H.
Dept. of Microbiology and Molecular Genetics
Michigan State University
E. Lansing, MI 48824
Medical Research: What is the background for this study? What are the main findings?
Dr. Manning: Diarrheal disease is a leading cause of morbidity and mortality in children under the age of five and is commonly caused by many different bacterial pathogens.
We have observed that infection with four different bacterial pathogens (Salmonella, Shigella, Shiga toxin-producing E. coli, and Campylobacter) all induce the proliferation of a population of microbes, namely Escherichia, which are already present in the gut of healthy individuals.
Dr. McKay[/caption]
MedicalResearch.com Interview with:
Brian S. McKay, Ph.D
Associate Professor
Department of Ophthalmology and Vision Science
University of Arizona
Medical Research Building, Room 212
Tucson, AZ 85724
Medical Research: What is the background for this study?
Dr. McKay: AMD (age-related macular degeneration) is a disease that is race-related. White people get the disease and lose vision to AMD at much higher rate than Blacks or Hispanics.
Thus, while race is complex, pigmentation may protect from the disease. With this starting point, my laboratory went after the pigmentation pathway to determine how pigment may affect photoreceptor (the retinal cells that actually catch the light) survival. The pigmented cells in the back of the eye are the retinal pigment epithelial cells (RPE), the rest of the retina does not pigment, it is clear not brown. We discovered that when the RPE make pigment they turn on molecular pathways to foster photoreceptor survival. Next we discovered the ligand for a receptor on the RPE that was tied to governing photoreceptor survival and pigmentation. That ligand was L-DOPA.
Knowing that L-DOPA is given to many aging individuals (those at risk of AMD), we developed a team to ask whether those taking L-DOPA for movement disorders are protected from AMD.
Dr. McCabe[/caption]
MedicalResearch.com Interview with:
Edward R. B. McCabe, MD, PhD
Senior Vice President and Chief Medical Officer
Professor Adjunct of Pediatrics
Yale University School of Medicine
Distinguished Professor Emeritus, Department of Pediatrics & Inaugural Mattel Executive Endowed Chair of Pediatrics, UCLA School of Medicine
Inaugural Physician-in-Chief, Mattel Children's Hospital
Chief Medical Officer March of Dimes
Medical Research: What is the background for this study? What are the main findings?
Dr. McCabe:
Dr. Barnes[/caption]
MedicalResearch.com Interview with:
Geoffrey Barnes, MD, MSc
Clinical Lecturer
Cardiovascular Medicine and Vascular Medicine
University of Michigan Health System
Medical Research: What is the background for this study?
Dr. Barnes: Although warfarin has been the primary anticoagulant used for stroke prevention in atrial fibrillation for over 60 years, four new direct oral anticoagulants (DOACs) have been introduced into the market since 2010. Dabigatran, which directly inhibits thrombin, was found to have better prevention of ischemic stroke and a significant reduction in hemorrhagic stroke (bleeding strokes) for patients with 


