Dr. Schlansky[/caption]
MedicalResearch.com Interview with:
Barry Schlansky, M.D., M.P.H
Assistant Professor of Medicine
Oregon Health & Science University
Medical Research: What are the main findings and significance of this study?
Dr. Schlansky: This study examines how obese patients fare before and after liver transplantation. Similar to other researchers, we found that obese patients do just as well as normal weight patients after liver transplantation. We were surprised, however, to find that very obese patients died more often while on the wait list before liver transplant.
Patrick Hardison before surgery (left) and in November 2015, nearly three months after the surgery.[/caption]
Mr. Hardison was referred to Dr. Eduardo D. Rodriguez, of NYU Langone Medical Center for consideration of facial transplantation.
Three months August 14, 2015 ago Dr. Rodriguez were able to give Patrick a new face, scalp, ears and ear canals, new eyelids and the muscles that control blinking.
Diana Frenier[/caption]
MedicalResearch.com Interview with:
Diane Frenier Esq
Reed Smith Corporate Partner
Member of Corporate & Securities Group and Life Sciences Health Industry Group
Background: Diane Frenier Esq discusses the M&A boom in the pharmaceutical and retail drug industry including a the "global study of 100 senior executives at life sciences companies by global law firm Reed Smith, in partnership with Mergermarket, reveals that 94% are planning to make an acquisition in the next year”.
Medical Research: What are the main drivers behind the pursuit of cross-border life sciences deals?
Ms Frenier: I think companies are trying to strengthen their capabilities in areas that are a core focus for them (e.g., in certain therapeutic areas, or for orphan drugs), and that includes adding products in those core focus areas and, in some cases, broadening geographically so they can market products in those core focus areas on a more global basis. This will allow them to use their resources more efficiently and take advantage of saving from reducing redundancies.
Dr. Givens
Dr. Marzolini[/caption]
MedicalResearch.com Interview with:
Susan Marzolini, R.Kin, PhD
Scientific Associate, TRI-REPS Supervisor
Toronto Rehab/UHN Cardiovascular Prevention and Rehabilitation Program
Medical Research: What is the background for this study? What are the main findings?
Dr. Marzolini: Coronary artery bypass graft (CABG) surgery is a leading revascularization procedure for treating coronary artery disease. Despite effective revascularization, cardiovascular risk factor control through intensive lifestyle and pharmacological treatment is essential to prevent graft deterioration and progression of atherosclerosis following surgery. Outpatient cardiac rehabilitation (CR) programs offer structured exercise, education, interdisciplinary support, counselling, and risk reduction to promote secondary prevention. These programs have been shown to improve fitness, psychosocial well-being, and significantly reduce morbidity and mortality after CABG surgery.
However, while Canadian and international guidelines endorse “early” referral to CR post-cardiac event, actual practice is variable and delays are common_ENREF_9_ENREF_9_ENREF_7. Delayed entry is of concern, as there is emerging evidence that later referral and initiation of cardiac rehabilitation is associated with negative consequences on cardiovascular fitness, however this has not been examined in the post-CABG population. Therefore, we conducted a retrospective analysis of 6497 consecutively enrolled post CABG participants in a single cardiac rehabilitation program in Toronto, Canada from January 1995 to October 2012. Our objective was to examine the effects of later entry on CR outcomes (i.e., CR use, anthropometrics, and functional capacity) while accounting for demographic, environmental, and physiological correlates of longer wait-time.
We found that longer wait-time to start a cardiac rehabilitation program was associated with poorer outcomes including less improvement in cardiopulmonary fitness and lower program attendance, which have been shown to confer a mortality disadvantage. Longer wait time was also associated with less improvement in body fat percentage as well as poorer completion rates. We identified that bypass patients predisposed to longer wait times, and subsequently poorer participation and outcomes, are women, those who are older, from a lower socioeconomic neighborhood, people with a more complex medical history, who are employed, have a longer drive-time to cardiac rehabilitation, and people with less social support.
Dr. Lin[/caption]
MedicalResearch.com Interview with:
Jiayuh Lin, Ph.D.
Associate Professor,
College of Medicine,
The Ohio State University
Medical Research: What is the background for this study? What are the main findings?
Dr. Jiayuh Lin: Pancreatic cancer is one of the most serious forms of cancer. Because of the poor response to chemotherapy as conventionally used, patients with any stage of pancreatic cancer may appropriately be considered candidates for clinical trials using novel agents.
IL-6 signaling plays an important role in oncogenesis and high serum IL-6 levels is a poor prognostic factor for overall survival in pancreatic cancer. Therefore, IL-6 is considered as a viable target for pancreatic cancer therapy. We utilized a drug discovery method with Multiple Ligand Simultaneous Docking and drug repositioning to identify an existing FDA-approved drug Bazedoxifene with previously unknown biological function as an IL-6/GP130 inhibitor. Bazedoxifene can inhibit cell viability of pancreatic cancer cells expressing IL-6 and suppressed pancreatic tumor growth in vivo.
Dr. Klempner[/caption]
MedicalResearch.com Interview with:
Samuel Klempner, M.D. Assistant Professor
Division of Hematology/Oncology
UC Irvine Health
Orange, CA 92868
Medical Research: What is the background for this study? What are the main findings?
Dr. Klempner: The background for our series is the concept that little is known about the genetic landscape of rare tumors such as acinic cell tumors, and that understanding genetic changes in tumors can identify treatment options. This paradigm can, and should, be extended beyond rare tumor types and many researchers are currently studying various tumor types. Another important background idea is that tumor genomic alterations may be more important than that anatomic site of origin. For example, I would argue that a breast cancer that harbors an EGFR mutation common to lung cancer could be treated similar to a lung cancer based on the genomic changes.
In our study we found another way that the BRAF protein and its downstream signaling may become activated through duplicating part of the protein called the kinase domain. This genetic event causes the pathway to be always "on" which is not normal, and likely drives cancer growth. However, BRAF kinase domain duplication appears sensitive to currently available drugs that target the BRAF pathway, as evidenced by the response in our patient. Thus, finding this change is important and may be able to guide a more personalized therapy choice. Importantly, we found BRAF kinase domain duplication across multiple different tumor types, suggesting this may be a recurrent event in some cancers. A very similar finding, involving duplication of the EGFR kinase domain, was also just reported (Cancer Discovery 2015;5:1155-1163) lending further validation to this mechanism of pathway activation in cancer.
Dr. Podo[/caption]
MedicalResearch.com Interview with:
Dr. Franca Podo, Dr Sci
Former Director of the Molecular and Cellular Imaging Unit
Department of Cell Biology and Neurosciences
Istituto Superiore di Sanità
Rome, Italy
Medical Research: What is the background for this study? What are the main findings?
Dr. Podo: Population-based studies showed that triple negative breast cancers (TNBCs), i.e. those which are negative for estrogen and progesterone receptors without HER-2/neu overexpression, have a more aggressive clinical course and a 2-to-3 fold higher likelihood of distant recurrence and death from breast cancer within 5 years from diagnosis, compared with non-TNBCs.
In a study published in Clinical Cancer Research (Online First 26 October 2015) Dr. F. Podo and Dr. F. Santoro (Istituto Superiore di Sanità, Rome) and Prof. F. Sardanelli (Università degli Studi di Milano, IRCCS Policlinico San Donato) in collaboration with other Italian co-authors, compared phenotype features and survival rates of invasive TNBCs versus non-TNBCs detected during the HIBCRIT-1 screening study of 501 asymptomatic women at high genetic-familial risk for breast cancer. The screening included BRCA1 and BRCA2 mutation carriers, as well as women with a strong family history of breast and/or ovarian cancer, enrolled between 2000 and 2008 in 18 centers. Data analysis from a median 9.7-year follow-up until June 2015 showed that, combining an annual screening including magnetic resonance imaging (MRI) with adequate treatment options, the mean 5-year overall survival of triple negative breast cancers was not significantly different from that of non-TNBCs (86% vs 93%), in spite of a 3-fold higher rate of cases of grade 3 invasive ductal carcinoma in the former subgroup (71% in TNBCs vs 23% in non-TNBCs). The mean disease-free survival rates were also very similar (77% vs 76%, respectively).
Dr. Chui[/caption]
MedicalResearch.com Interview with:
Helena Chui, Ph.D.
CPsychol Lecturer Division of Psychology
University of Bradford
Bradford England
Medical Research: What is the background for this study? What are the main findings?
Dr. Chui: It is debatable whether psychological well-being improves or declines with age. Findings of the age-related changes in psychological well-being, life satisfaction, and depressive symptoms, are not unequivocal. Some studies have found that people stay pretty stable in terms psychological well-being until late life. Other studies have found otherwise. My recent publication reports the findings using a 15-year longitudinal study from Australia. Results showed that as people get older, depressive symptoms increase. Both men and women reported increasingly more depressive symptoms as they aged, with women initially starting with more depressive symptoms than men. However, men showed a faster rate of increase in symptoms so that the difference in the genders was reversed at around the age of 80.
Dr. Qin[/caption]
MedicalResearch.com Interview with:
Bo (Bonnie) Qin, PhD
Postdoctoral associate at Rutgers Cancer Institute of New Jersey
Medical Research: What is the background for this study? What are the main findings?
Response: Ovarian cancer is among the top five causes of cancer death among women in the US. Compared to white women, African-American women tend to have a worse 5-year survival rate of ovarian cancer. It highlights a critical need for identifying preventive factors in African Americans, particularly through dietary modification, which is relatively low cost and low risk compared to medical treatments.
We found that adherence to an overall healthy dietary pattern i.e. Alternate Healthy Eating Index (AHEI)-2010 may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal women. Adherence to the current Dietary Guidelines for Americans i.e. Healthy Eating Index-2010, were also strongly associated with reduced risk of ovarian cancer among postmenopausal African-American women.
MedicalResearch.com Interview with:
Shahrzad Mavandadi, PhD
Research Health Science Specialist and Investigator
Veterans Integrated Services Network 4 Mental Illness Research,
Education, and Clinical Center
Corporal Michael J. Crescenz Veterans Affairs Medical Center
Philadelphia, Pennsylvania
Medical Research: What is the background for this study?
Dr. Mavandadi: Mental health (MH) conditions are underidentified and undertreated in later life. This is particularly true among subgroups of older adults who are more vulnerable to developing mental health issues, have poor access to specialty care, and are less responsive to treatment and therapy. Thus, we sought to evaluate longitudinal MH outcomes among low-income, community-dwelling older adults enrolled in an evidence-based, collaborative mental health care management service (i.e., the SUpporting Seniors Receiving Treatment And INtervention (SUSTAIN) program). The SUSTAIN program integrates mental health with primary care (which is where the majority of behavioral health conditions in later life are managed) and provides standardized, measurement-based, software-aided MH assessment and connection to community resources to older adults by telephone.
While there is a strong evidence base for the efficacy of collaborative care models for me conditions, little is known about the amount or level of patient and provider support that is needed to achieve optimal behavioral health outcomes. Thus, we specifically examined outcomes among older adults randomized to one of two program arms of varying intensity: MH symptom monitoring alone or mental health symptom monitoring plus MH care management. MH care management involved care managers who provided education, counseling, and decision support to patients and their primary care providers, a licensed mental health clinician who supervised the care managers, and the use of an algorithm to help guide pharmacological and non-pharmacological treatment plans. The sample consisted of 1018 older adults prescribed an antidepressant or anxiolytic by their non-behavioral health providers who presented with clinically significant symptoms at intake.
Dr. Del Gobbo[/caption]
MedicalResearch.com Interview with:
Liana Del Gobbo PhD
Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA; and
Life Sciences Research Organization, Bethesda, MD
Medical Research: What is the background for this study? What are the main findings?
Dr. Del Gobbo: Accumulating evidence suggests that nut intake lowers risk of cardiovascular disease. But the specific mechanisms by which nuts may exert beneficial effects (eg. through lowering blood cholesterol, blood pressure, inflammation, etc.) were not clear. Two prior reviews on this topic only evaluated one type of nuts, and only a few cardiovascular risk factors.
To address these knowledge gaps, we performed a systematic review and meta-analysis of controlled trials to examine the effects of eating tree nuts (walnuts, pistachios, macadamia nuts, pecans, cashews, almonds, hazelnuts, Brazil nuts) on major cardiovascular risk factors including blood lipids (total cholesterol, LDL, HDL, triglycerides [TG]), lipoproteins (ApoA1, ApoB, ApoB100), blood pressure (systolic, SBP; diastolic, DBP), and inflammation (C-reactive protein, CRP) in adults 18 years or older without cardiovascular disease.
A daily serving of nuts (1oz serving, or 28g per day) significantly lowered total cholesterol, LDL, ApoB, and triglycerides, with no significant effects on other risk factors, such as HDL cholesterol, blood pressure or inflammation. To give you an idea of a 1oz serving size of nuts, it is about 23 almonds, 18 cashews, 21 hazelnuts, 6 Brazil nuts, 12 macadamia nuts, 14 walnut halves, 20 pecan halves, 49 pistachios.
We did not see any differences in cholesterol-lowering effects by nut type.
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. In addition, children born to women with higher serum PFOA concentrations during pregnancy gained more fat mass between 2 and 8 years of age than children born to women with lower 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.
MedicalResearch.com Interview with:
Jasvinder Singh MD MPH
Professor of Medicine
UAB Division of Clinical Immunology and Rheumatology
Medical Research: What is the background for this study? What are the main findings?
Dr. Singh: A systematic review of the effect of smoking on outcomes after total joint replacement showed that current smoking increased the risk of overall post-operative complications but that there were scarce data for smoking and specific surgical outcomes of arthroplasty. We performed a study using data from an institutional Total Joint Registry to answer this question. In a study of for 7,926 patients who underwent hip or knee arthroplasty, 7% were current tobacco users. We found that compared to current non-users, current tobacco users had higher hazard ratios (95% CI) for deep infection, 2.37 (1.19, 4.72; p=0.01) and implant revision, 1.78 (1.01, 3.13; p=0.04) after total hip or knee arthroplasty. No significant differences were noted for periprosthetic fractures or superficial infections.
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. Tracy Wang[/caption]
MedicalResearch.com Interview with:
Dr. Tracy Wang MD MHS MSc
Assistant Dean, Continuing Medical Education
Director, Center for Educational Excellence
Fellowship Associate Program Director
Associate Professor of Medicine, Cardiology
Duke Clinical Research Institute
Medical Research: What is the background for this study? What are the main findings?
Response: Medication non-adherence is a known challenge in the management of patients with coronary artery disease. Barriers to adherence are multifactorial, attributed to patient, healthcare provider, and social determinants. However, whether patient medication adherence varies across different hospitals is unknown. In this study, we sought to determine whether inter-hospital differences exist in the degree of patient adherence to secondary prevention medications after discharge. Moreover, we assessed whether these hospital-specific variations in medication adherence, if any, correspond to downstream patient outcomes.
We observed that the majority of post-MI patients were prescribed guideline-recommended secondary prevention medications at discharge. However, among those prescribed, we see a significant decline in the use of these medications within just 90 days after discharge. Medication adherence rates varied markedly across U.S. hospitals, with the widest variation seen for post-discharge use of beta-blockers. Hospitals with high post-discharge medication adherence were associated with significantly lower risk of major adverse cardiovascular events and death or all-cause readmissions when compared with hospitals with low adherence rates, even after adjustment for differences in patient case-mix.
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 low-calorie sweeteners was mostly not representative of how people consume low-calorie sweeteners.
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 epilepsy. Whether this link reflected an overlap in the genetics of the two conditions has remained a mystery, however. In this study, we used a recently developed computational technique to show that there is a significant positive correlation between the genetic variants that are associated with epilepsy and with those that are associated with schizophrenia.