Author Interviews, Education, JAMA, OBGYNE, Pediatrics, Social Issues / 21.12.2018

MedicalResearch.com Interview with "Pregnancy 1" by operalynn is licensed under CC BY 2.0Josephine Funck Bilsteen, MSc Department of Pediatrics, Hvidovre University Hospital, Hvidovre, Section of Epidemiology, Department of Public Health University of Copenhagen Copenhagen, Denmark MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The background of this study is that there is increasing recognition of the longer-term health and social outcomes associated with preterm birth such as independent living, quality of life, self-perception and socioeconomic achievements. However, much less is known about differences in education and income among adults born at different gestational weeks in the term period. In this study shorter gestational duration, even within the term range, was associated with lower chances of having a high personal income and having completed a secondary or tertiary education at age 28 years. This is the first study to show that adults born at 37 and 38 completed weeks of gestation had slightly lower chances of having a high income and educational level than adults born at 40 completed weeks of gestation.  (more…)
Author Interviews, Cancer Research, NEJM, Pancreatic / 21.12.2018

MedicalResearch.com Interview with: Prof. Thierry Conroy MD, Director Department of Medical Oncology Institut de Cancérologie de Lorraine Vandoeuvre-lès-Nancy CEDEX MedicalResearch.com: What is the background for this study? Response:  Surgery of pancreatic cancer offers the only chance of cure. Despite the low response rate (5% - 9%) of gemcitabine in metastatic disease, a 6-month regimen of adjuvant therapy with gemcitabine increases 5-year survival from 10% to 20% and is recognized as standard of care. However, recurrence rate remain high despite adjuvant treatment with 69-75% of patients relapsing within 2 years. -       The combination of bolus and continuous infusion Fluorouracil, Folinic Acid, Irinotecan and Oxaliplatin (Folfirinox) was shown to increase response rate (31.6% versus 9.4%) in metastatic disease as compared to Gemcitabine and increase survival (11.1 versus 6.8 months). -       Deletion of bolus Fluorouracil in the Folfirinox regimen (mFOLFIRINOX) decreased toxicity and do not reduce efficacy in advanced disease. -       We performed a randomized trial in patients with good performance status, ECOG 0-1 CA 19.9 ≤ 180 U/L and no cardiac contraindication to fluorouracil. (more…)
Author Interviews, Bone Density, NEJM, Orthopedics / 21.12.2018

MedicalResearch.com Interview with: Prof Ian Reid MD Faculty of Medical and Health Sciences University of Auckland Auckland New Zealand MedicalResearch.com: What is the background for this study?  Response: Bisphosphonates prevent fractures in patients with osteoporosis, but their efficacy in women with osteopenia is unknown. Most fractures in postmenopausal women occur in osteopenic patients, so therapies with efficacy in osteopenia are needed. (more…)
Author Interviews / 20.12.2018

By: The Experts at Child Safety Store
  • It is recommended that the majority of your childproofing be done at one time. This insures that it is completed before a new capability results in a preventable injury.
  • All lower drawers and cabinets in the kitchen and bathrooms should be latched before he ever learns he can open them. Accessible electrical outlets (both dormant and in-use) protected, vertical cords raised, pool fence installed, stairway gates in place, sharp corners protected, etc. Other items can be added as the need becomes apparent; door alarms, appliance latches, medicine cabinet latches, door knob covers, deadbolt locks, etc.
  • Get down on your child’s level (that’s hands, knees, roll over on your back to get under furniture) and look up. Look around each room carefully as if seeing it for the first time. Crawl around and try to stick your head behind furniture, reach under furniture and feel around to see what is there (sharp springs or staples sticking out, plastic tags, etc.). Get under tables and look up; what would your child’s head hit if he stood up (sharp corners, manufacturer’s labels attached with staples sticking out, glass in the center of an end stand or coffee table).
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Author Interviews, Dermatology, JAMA, NYU / 19.12.2018

MedicalResearch.com Interview with: Nicholas A. Soter, MD The Ronald O. Perelman Department of Dermatology New York University School of Medicine New York, New York MedicalResearch.com: What is the background for this study? Response: Nearly 50% of patients with chronic spontaneous urticarial (CSU) (hives) incompletely respond to first-line therapy with H-1 antihistamines. However, in the current literature, there is limited evidence to guide the treatment of CSU after maximal therapy with antihistamines fails.  Two small, randomized, controlled trials suggest that dapsone, which is an antimicrobial therapeutic agent with anti-inflammatory properties, may be a useful second-line therapeutic agent. (more…)
Author Interviews, Orthopedics, Pediatrics / 19.12.2018

MedicalResearch.com Interview with: Dana L. Duren, PhD Professor, Director of Orthopaedic Research Director of Skeletal Morphology Laboratory Thompson Laboratory for Regenerative Orthopaedics Department of Orthopaedic Surgery Missouri Orthopaedic Institute, University of Missouri Columbia, MO 6521 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The motivation for this study is the apparent accelerated maturity in children in the United States.   We previously demonstrated that skeletal maturity (bone age) is more advanced in today’s children compared to children born in the first half of the 20thCentury (Duren et al., 2015). n the current study (Boeyer et al., 2018) we show that a significant component of this advanced maturity status is the timing of epiphyseal fusion. In our study, nearly half of the epiphyses of the hand and wrist began or completed fusion significantly earlier in children born after 1995 than those born in the early part of the century, with differences as great as six to ten months for some bones, and mean differences on the order of 4 months in boys and 6 months in girls.  (more…)
Author Interviews, Brigham & Women's - Harvard, JAMA, OBGYNE, Pediatrics / 19.12.2018

MedicalResearch.com Interview with: Krista F. Huybrechts, MS PhD Associate Professor of Medicine Brigham and Women’s Hospital Harvard Medical School Boston, MA 02120  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Pregnant women often experience nausea and vomiting, particularly during the first trimester.  Early treatment is recommended to relieve symptoms and prevent progression to hyperemesis gravidarum.  Although not formally approved for this indication, ondansetron is the most frequently prescribed treatment for nausea and vomiting in pregnancy in the US: 22% of pregnant women reportedly used ondansetron in the US in 2014. Despite this common use, the available evidence on the fetal safety of ondansetron is limited and conflicting, and the possibility of a doubling in risk of cleft palate and cardiac malformations has been raised. We therefore evaluated the association between ondansetron exposure during the first trimester of pregnancy, the period of organogenesis, and the risk of congenital malformations in a cohort of 1,816,414,publicly insured pregnancies using the nationwide Medicaid Analytic eXtract data for 2000-2013.  A total of 88,467 women (4.9%) were exposed to ondansetron during the first trimester.  After adjusting for a broad range of potential confounding variables, we found no association with cardiac malformations (RR = 0.99; 95% CI, 0.93 – 1.06)  and congenital malformations overall (RR = 1.01; 95% CI, 0.98 – 1.05). For oral clefts, we found a 24% increase in risk (RR=1.24; 95% CI, 1.03 – 1.48), which corresponds to an absolute risk of 2.7 per 10,000 births (95% CI, 0.2 – 5.2 per 10,000 births).  These findings were consistent across sensitivity analyses, conducted to address potential misclassification and confounding bias.  (more…)
Author Interviews, Brigham & Women's - Harvard, Cannabis, JAMA, Mental Health Research, Pediatrics / 19.12.2018

MedicalResearch.com Interview with: Sharon Levy, MD, MPH Director, Adolescent Substance Use and Addiction Program Boston Children's Hospital Associate Professor of Pediatrics Harvard Medical School  MedicalResearch.com: What is the background for this study? What are the main findings? Response: ​For this study we analyzed data that were collected as part of a larger survey study that recruited a sample of adolescents who were coming to the doctor's office for routine medical care.  We asked them a lot of questions about their health, school, extracurricular activities, plans for the future, substance use patterns and problems associated with use among other things. The main finding was that among the participants who reported marijuana use in the past year, many of them, more than 40%, said that they had experienced either an hallucination, or paranoia/anxiety related to their use. Kids who used more frequently and those who met criteria for a substance use disorder were more likely to experience these symptoms, as were those who had symptoms of depression (more…)
Author Interviews, Heart Disease, Women's Heart Health / 19.12.2018

MedicalResearch.com Interview with: Dr. Sarah Perman MD, M.S.C.E. Assistant professor of Emergency Medicine University of Colorado School of Medicine Denver  MedicalResearch.com: What is the background for this study? Response: Women who suffer an out-of-hospital cardiac arrest have been observed to receive less bystander cardiopulmonary resuscitation (B-CPR) than men, and the potential reasons were largely unknown. We asked 54 people online to explain – with no word limit – why women might be less likely to get CPR when they collapse in public. (more…)
Allergies, Author Interviews, OBGYNE, Pediatrics / 18.12.2018

MedicalResearch.com Interview with:  Karen Robbins, M.D. Allergist at Children’s National Health System  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The background is that mothers are often concerned that something they did contributed to their children developing food allergies. Many will relate that they ate a lot of one specific food allergen while pregnant, and question how this could have impacted their unborn child. We realized that we hear a lot of anecdotal stories in clinic, but were not sure how frequently mothers try to alter their diet in the hopes of preventing food allergy in their children. We also were not sure where families get information or guidance on this topic. (more…)
Author Interviews, Electronic Records, Mental Health Research / 18.12.2018

MedicalResearch.com Interview with: Katharine Phillips, M.D. Professor of Psychiatry DeWitt Wallace Senior Scholar Residency Research Director Department of Psychiatry Weill Cornell Medical College, Cornell University Attending Psychiatrist, New York-Presbyterian Hospital Adjunct Professor of Psychiatry and Human Behavior Alpert Medical School of Brown University Weill Cornell Psychiatry Specialty Center Weill Cornell Medicine I NewYork-Presbyterian MedicalResearch.com: What is the background for this study? What are the main findings?
  • Electronic prescribing of medication by clinicians is widespread; it is required in many institutions and in some states. Electronic prescribing systems commonly use computerized decision support algorithms that give prescribers automated warnings or alerts at the time of prescribing if the system identifies a potential prescribing error.
  • Some prior studies suggest that electronic prescribing warnings/alerts may reduce prescribing errors and thus can be clinically useful. However, other prior studies caution that these alerts may have substantial limitations.
  • Despite the importance of this topic, relatively few studies have examined the accuracy of automated prescribing warnings in electronic prescribing systems; to our knowledge, no prior study has focused primarily on prescribing of medications for psychiatric conditions.
  • This report presents results from a survey of members of the American Society of Clinical Psychopharmacology (ASCP), a specialty society that advances the science and practice of clinical psychopharmacology, regarding automated warnings generated by electronic prescribing systems.
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Author Interviews, Cancer Research, Herpes Viruses / 18.12.2018

MedicalResearch.com Interview with: Jiahui Qian, MPH School of Public Health and Community Medicine University of New South Wales Sydney Australia     MedicalResearch.com: What is the background for this study? Response: Herpes zoster is a neurocutaneous disease caused by the reactivation of latent varicella zoster virus and its risk is related to the cell-mediated immunity. Previous studies have reported a higher zoster risk among patients with haematological cancer and cancer patients receiving chemotherapy. However, the role of the cancer itself and the receipt of cancer treatment is not clearly separated, we therefore started this study and tried to separate the risk of zoster associated with the cancer itself from cancer treatment.  (more…)
Author Interviews, Social Issues / 18.12.2018

MedicalResearch.com Interview with: Alice Verstaen, PhD VA Puget Sound Health Care System  MedicalResearch.com: What is the background for this study? Response: The study began in the 1980s in Dr. Levenson’s laboratory at the University of California, Berkeley in collaboration with Dr. John Gottman of the University of Washington and Dr. Laura Carstensen at Stanford University. Prior to this study, most research on marriage had focused on younger marriages that ended in separation and divorce. Our study was designed to focus on marriages that had lasted for many years. The idea was that these successful longer-term marriages could provide important clues as to what makes marriages succeed and stay together over time.  (more…)
Author Interviews, Compliance, Electronic Records, JAMA, Ophthalmology / 18.12.2018

MedicalResearch.com Interview with: Michael Vincent Boland, M.D., Ph.D. Glaucoma Center of Excellence Director of Information Technology, Wilmer Eye Institute Associate Professor of Ophthalmology Johns Hopkins University School of Medicine Baltimore, Maryland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Effective medications are available to treat glaucoma and prevent or stop vision loss.
Unfortunately, patients frequently do not use the eye drops as prescribed, oftentimes simply
because they forget to. Since patient medications are now managed via electronic health
records (EHRs), we built a system to deliver automated reminders to patients using the patient
portal to our EHR. We found that the majority (75%, 66 of 88) of participants that received these reminders found them to be useful, and about half (47%, 41 of 88) the participants wanted to
continue using the reminders after the study ended
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Author Interviews, Johns Hopkins, Kidney Disease, Transplantation / 18.12.2018

MedicalResearch.com Interview with: Chirag R Parikh, M.B.B.S., Ph.D. Director,Division of Nephrology Professor of Medicine School of Medicine, Johns Hopkins University Baltimore, Maryland 21287  MedicalResearch.com: What is the background for this study? Response: The initial study idea stemmed from our earlier cohort studies of predictors of delayed graft function after kidney transplantation.  We previously found that kidneys from donors with Acute Kidney Injury (AKI) were more often discarded than kidneys from donors without AKI, and transplanted donor AKI kidneys were at increased risk for delayed graft function. It was important to determine whether that increased risk for delayed graft function also translated into worse long-term outcomes for recipients of kidneys from donors with AKI. (more…)
Author Interviews, Genetic Research, Nutrition / 18.12.2018

MedicalResearch.com Interview with: Denny Vågerö  PhD MSc CHESS, Centre for Health Equity Studies Department of Public Health Sciences Stockholm University, Stockholm, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: Transgenerational, epigenetic, response, has been shown in studies of animals and plants. Does it apply to humans? Previous findings of associations between grandparents early nutrition and grandchildren’s mortality have been controversial.  Two reasons for this: evidence in human studies has been based on rather small numbers and potential mechanisms are not very well understood. We have tested the hypothesis that there is “a male line transgenerational response” to nutritional events in pre-puberty in a study much larger than previous ones. We find support for this hypothesis in that boys who enjoyed unusually good access to food during their “slow growth period” (aged 9-12 years) seem to transmit a mortality risk on their grandsons but not granddaughters, in particular for cancer. (more…)
Author Interviews, Diabetes, JAMA, Pain Research / 17.12.2018

MedicalResearch.com Interview with: Guy Fagherazzi, MSc, PhD, HDR Senior Research Scientist in Digital & Diabetes Epidemiology Center of Research in Epidemiology and Population Health Inserm, Paris-South Paris-Saclay University MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Migraine has further been associated with increased risk of overall and specific cardiovascular disease events. Because migraine has also been associated with factors related with insulin resistance and type 2 diabetes, an association between migraine and diabetes has been hypothesized. We observed a lower risk of type 2 diabetes in women with active migraine. We also show a linear decrease of migraine prevalence long before and a plateau long after type 2 diabetes diagnosis.  (more…)
Author Interviews, Blood Pressure - Hypertension, Critical Care - Intensive Care - ICUs, Emergency Care, JAMA / 17.12.2018

MedicalResearch.com Interview with:
"intravenous" by thorney torkelson is licensed under CC BY-NC-ND 2.0 <a href="https://creativecommons.org/licenses/by-nc-nd/2.0"> CC BY-NC-ND 2.0</a>Daniel J. Lane PhD
Institute of Health Policy, Management and Evaluation
Dalla Lana School of Public Health, University of Toronto
Rescu, Li Ka Shing Knowledge Institute, St Michael’s Hospital
Toronto, Ontario, Canada

MedicalResearch.com:  What is the background for this study?  What are the main findings?

Response: Early resuscitation and early antibiotics have become the mainstay treatment for patients with sepsis. The time to initiation of these treatments is thought to be an important factor in patients surviving their disease; however, the independent benefits or harms of intravenous fluid resuscitation, in particular a more aggressive versus more conservative approach to this therapy, remains difficult to evaluate given the concurrent use of these therapies in hospital.

To gain a better understanding of this treatment independent of antibiotic use, we assessed intravenous fluid resuscitation by paramedics on the in-hospital mortality of patients with sepsis. By accounting for the interaction between initial systolic blood pressure and the treatment, we found that earlier resuscitation by paramedics was associated with decreased mortality in patients with low initial blood pressures but not associated with mortality for patients with normal or higher initial blood pressures. 

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Alcohol, Author Interviews / 16.12.2018

MedicalResearch.com Interview with: "Schott Zwiesel Wine Glasses" by Didriks is licensed under CC BY 2.0 <a href="https://creativecommons.org/licenses/by/2.0"> CC BY 2.0</a>Simona Costanzo MS, PhD Laboratory of Molecular and Nutritional Epidemiology, Department of Epidemiology and Prevention. IRCCS Istituto Neurologico Mediterraneo Neuromed, Italy MedicalResearch.com: What is the background for this study? What are the main findings?  Response: We investigated how the different intake of alcohol relates to all-cause and cause-specific hospitalizations. In particular, we mainly investigated the association of alcohol consumption with total number of hospitalizations that occurred during 6 years of follow-up. We also examined cause-specific hospitalizations (e.g., alcohol-related diseases, vascular diseases, cancer, traumatic injury, and neurodegenerative diseases). (more…)
Author Interviews, Cancer Research, Dermatology / 15.12.2018

MedicalResearch.com Interview with: Dr. Kristine A. Romine MD CEO and Founder of Camelback Dermatology & Skin Surgery Phoenix, AZ MedicalResearch.com: Would you give a brief overview of the different types of skin cancer? Response: There are multiple types of skin cancer, including: melanoma, basal cell carcinoma, squamous cell carcinoma, and actinic keratosis. Known as the deadliest form of skin cancer, melanoma develops when irreparable DNA damage results in malignant transformation of melanocytes. This type of skin cancer is most commonly caused by intense UV exposure from the sun or tanning beds, which activate mutations that lead skin cells to rapidly multiply and form malignant tumors. Melanoma can range in color from dark brown to black and are rarely red or even skin colored. They are usually irregular and asymmetrical. In 2018, there were an estimated 91,270 new cases of melanoma (American Cancer Society, 2018). Basal cell carcinoma (BCC) is the most common type of skin cancer and cancer diagnosed. BCCs arise in the skins’ outermost layers. BCCs resemble open sores, red or pink plaques, pearly nodules with telangiectasia, or scars. It is estimated that 4.3 million BCCs are diagnosed in the U.S. every year (Skin Cancer Foundation, 2018). Squamous cell carcinoma (SCC), the second most common type of skin cancer, arises from the squamous cells in the skin that have been exposed to UV over long periods of time. SCCs appear as scaly red or pink macules, papules, or plaques. They can be crusted and appear eroded and can commonly arise within a solar keratosis. More than 1 million cases of SCC are diagnosed in the U.S. every year (Skin Cancer Foundation, 2018). Lastly, actinic keratoses (AKs) are the most common pre-cancerous skin growth that can develop into a SCC if left untreated. Similar to all other types, AKs are caused by exposure to UV light and, in rare cases, high exposures to x-rays. AKs can appear on sun-exposed areas, including the face, scalp, ears, shoulders, and legs. They resemble pink, scaly rough patches on the skin. (more…)
Author Interviews, Sleep Disorders / 14.12.2018

MedicalResearch.com Interview with: Brandon Hauer, Neuroscience PhD Student Neuroscience and Mental Health Institute Clayton Dickson, Professor Departments of Psychology, Physiology, and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our lab is interested in the dynamics of sleep and sleep-like rhythms in the forebrain. One particular interest relates to how the brain can spontaneously switch between very different states like rapid eye movement sleep (REM, or dreaming sleep) and slow-wave sleep (deep, restorative stage of sleep). We noticed that administering 100% oxygen to rats in an anesthetized preparation that closely models natural sleep produced an immediate and lasting switch into a slow-wave brain state. This happened as well in naturally sleeping rats. Interestingly, increasing carbon dioxide concentrations or decreasing oxygen in inspired air produced the opposite effect, namely a switch into activated or REM-like states.  (more…)
Author Interviews / 13.12.2018

MedicalResearch.comInterview with:

Hadi Shafiee, PhD Assistant Professor of Medicine Division of Engineering in Medicine Brigham and Women's Hospital

Hadi Shafiee, PhD
Harvard Medical School
Assistant Professor of Medicine
Division of Engineering in Medicine
Brigham and Women's Hospital
Harvard Medical School

 

MedicalResearch.com:  What is the background for this study?  What are the main findings?

Response: Last year we developed a smartphone-based technology for male infertility testing at-home, which was published at Science Translational Medicine. This year, we developed a similar technology for ovulation testing at-home. Here, we developed a 3D printed smartphone-attachment similar to a cellphone case that literally turns the phone to a small microscope. 

This low-cost smartphone attachment magnifies the saliva fern structures dried on a reusable device that will be  recorded using the smartphone camera. The entire sample-to-answer time is only few minutes (~7 mins). The developed ovulation test is fully automated, simple, and easy-to-use. 

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Author Interviews, Blood Pressure - Hypertension / 13.12.2018

MedicalResearch.comInterview with:

Eric J. BELIN de Chantemèle, D.Sc. Associate Professor Department of Medicine, Cardiology Augusta University

Eric J. Belin de Chantemèle, D.Sc.
Associate Professor
Department of Medicine, Cardiology
Vascular Biology Center
Medical College of Georgia at Augusta University

Jessica L Faulkner, PhD
Post-doctoral Fellow
Vascular Biology Center
Medical College of Georgia at Augusta University

MedicalResearch.com:  What is the background for this study?  What are the main findings?

Response: It is generally accepted in the medical community that women are more salt sensitive than men. By “salt sensitive” we mean that blood pressure increases with increases in salt in the diet.

While we have known for a long time that women are more likely to experience problems with their blood pressure that are associated with the salt that they eat, the reasons why remain largely unknown and, therefore, the best way to treat it is also unknown. With the average American eating roughly twice the salt recommended by the American Heart Association guidelines, the effects of dietary salt on blood pressure are very important. Our latest publication in the journal American Heart Association’s journal Hypertension shows that female mice are more prone to high blood pressure when on a high salt diet than males.

MedicalResearch.com: What should readers take away from your report?

Response: Our report begins to shed some light on why women may have a greater risk of developing high blood pressure due to eating too much salt. We recently found that a hormone, termed “aldosterone” is acting inappropriately in females in response to a lot of salt in the diet. In healthy individuals who are not salt sensitive, aldosterone is decreased by salt in the diet and is protective to the blood vessels. However, in female mice it is less likely that aldosterone will be decreased, and this lack of decrease of aldosterone leads to blood vessel damage and high blood pressure in our study.In contrast, our male mice in our study suppressed aldosterone when given a high salt diet, and did not develop blood vessel damage or high blood pressure.We believe this variation in aldosterone production in women may be a reason why they are clinically more likely to have a blood pressure response to high salt diets.

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Author Interviews / 12.12.2018

MedicalResearch.comInterview with:

Tetsuo Shoji, MD, PhD. Department of Vascular Medicine Osaka City University Graduate School of Medicine Osaka Japan
Dr. Shoji

Tetsuo Shoji, MD, PhD.
Department of Vascular Medicine
Osaka City University Graduate School of Medicine
Osaka Japan

MedicalResearch.com:  What is the background for this study?  What are the main findings?

Response: Vitamin D is known to be associated with health and disease of various organs such as bone, heart, brain, and others. Vitamin D is activated by the liver and kidneys to a hormone called 1,25-dihydroxyvitamin D which binds to vitamin D receptor in cells to exert its functions.

Vitamin D activation is severely impaired in patients with kidney disease requiring hemodialysis therapy, leading to mineral and bone disorder(MBD). Therefore, active form of vitamin D is one of the standard choices of treatment for MBD caused by kidney function loss.

Previous observational cohort studies showed that the use of active vitamin D in hemodialysis patients was associated with lower likelihood of all-cause death, cardiovascular death, and incident cardiovascular disease.Potentially cardio-protective effects of active vitamin D were shown by basic studies using cultured cells and animal models. Then, many nephrologists began to believe that active vitamin D is a “longevity hormone” or a “panacea” for kidney patients requiring dialysis therapy, although there was no evidence by randomized clinical trials. 

To show evidence for it, we conducted a randomized clinical trial namedJ-DAVID in which 976 hemodialysis patients were randomly assigned to treatment with oral alfacalcidol or treatment without active vitamin D, and they were followed-up for new cardiovascular events during the four-year period. The risk of cardiovascular events was not significantly different between the two groups. The risk of all-cause death was not significantly different either.

To our surprise, the risk of cardiovascular event tended to be higher in the patients who continued treatment with active vitamin D than those who continued non-use of active vitamin D, although the difference was not statistically significant.

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Author Interviews, Cancer Research / 12.12.2018

MedicalResearch.comInterview with:
Alexandra Avgustinova PhD
Postdoctoral fellow at the Institute for Research in Biomedicine (IRBBarcelona)

Dr. Avgustinova
Dr. Avgustinova

MedicalResearch.com:  What is the background for this study?

Response: The basis of this study was the strong association between closed chromatin and high mutation rate reported several years ago. We were surprised to see this observation being widely interpreted as a causal association, as it was largely based on correlative studies without experimental backing. Therefore we decided to experimentally test for the first time whether indeed altering chromatin opening would affect mutation rate or distribution within tumours.

MedicalResearch.com: What are the main findings?

Response: We found that, despite significantly increasing chromatin opening, loss of the histone methyltransferase G9a did not have any major influence on the mutation rate or distribution within cutaneous squamous cell carcinomas. These results demonstrate that chromatin opening does not play a major role in determining the mutation rate within tumours, and we speculate that other, confounded factors (e.g. replication timing or H3K36me3 levels) are likely causal for the observed association. This, however, remains to be proven experimentally.

Another major conclusion of our study was that although tumour initiation was delayed and tumour burden decreased in the absence of G9a, the tumours that did develop were highly aggressive due to selection for more aggressive tumour clones. This finding was contrary to many published reports suggesting G9a as a good candidate for clinical targeting, highlighting the need for long-term follow-up in pre-clinical studies.

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Author Interviews / 12.12.2018

MedicalResearch.comInterview with:

Zhaohui Gu, PhD
Postdoctoral Research Associate
 St. Jude Children's Research Hospital, TN

MedicalResearch.com:  What is the background for this study?  What are the main findings?

Response:B-progenitor acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy and the leading cause of childhood cancer death. B-ALL includes multiple subtypes that are defined by distinct genetic alterations and that play an important role in diagnosis, prognosis and therapy of patients.  Advances in transcriptome sequencing (RNA-seq)have helped researchers discover additional subtypes and driver mutations inB-ALL and identify possible new therapeutic targets.  Still, up to 30% of B-ALL cases do not fit into established subtypes. These patients lack targeted therapeutic approaches and commonly relapse.

Fort his study, we used integrated genomic analysis of 1,988 childhood and adult cases to revise the classification system of B-ALL. The system includes eight new subtypes and a total of 23 B-ALL subtypes. The subtypes are defined by chromosomal rearrangements, sequence mutations, or heterogeneous genomic alterations. Many show a marked variation in prevalence according to age.

The newly identified subtypes included one (n=18) defined by rearrangements of gene BCL2, MYC and/or BCL6 anda distinctive gene expression profile (GEP). Patients in this subtype were mostly adults (n=16) with very poor outcomes.

Another novel subtype was defined by IKZF1 N159Y missense mutation. N159Y is in the DNA-binding domain of IKZF1, and is known to disrupt IKZF1 function, with distinct nuclear mis-localization and induction of aberrant intercellular adhesion. There were eight cases in this subtype that shared highly similar GEPs.

We also identified two subtypes with distinct GEP and characterized by PAX5 alterations. One, PAX5 altered (PAX5alt), included 148 cases. PAX5alt was characterized by diverse PAX5 alterations including rearrangements (n=57), sequence mutations (n=46) and/or focal intragenic amplifications (n=8). These PAX5 alterations were found in 73.6% of PAX5alt cases. The second distinct subtype comprised 44 cases, all with PAX5 P80R missense mutations. Bi-allelic PAX5 alterations were commonly seen in this subtype in the form of PAX5 P80R coupled with a second sequence mutation or deletion of the wild-type PAX5 allele.

Adult PAX5 P80R cases showed better 5-year OS (61.9±13.4%) than those in PAX5alt subtype (42.1±10.2%). In addition, Pax5 P80R heterozygous and homozygous mice developed B lineage leukemia with a median latency of 166 and 87 days, respectively.  The heterozygous mice acquired alterations on the second allele, which faithfully recapitulated the condition of the patient leukemia.

MedicalResearch.com: What should readers take away from your report?

Response: Identification of subtypes accurately is very important for diagnosis, intensity-tailored therapy, and to identify targetable lesions. In this large scale genomic study, we demonstrated the power of using RNA-seq to classifying B-ALL and established a revised B-ALL taxonomy with 23 distinct subtypes. We identified 8 novel subtypes, including two defined by PAX5 alterations. Through in vitro and in vivo experiments, we demonstrated that PAX5 P80R could impair B cell differentiation and initiate leukemia.

Together with the subtype defined by IKZF1 N159Y mutation, we showed for the first time that transcription factor missense mutations could be a subtype defining genetic lesions.

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Author Interviews, Cancer Research / 12.12.2018

MedicalResearch.comInterview with:

Zhen Gu, Ph.D. Professor, Department of Bioengineering University of California, Los Angeles (UCLA)
Dr. Zhen Gu

Zhen Gu, Ph.D.
Professor, Department of Bioengineering
University of California, Los Angeles (UCLA)

MedicalResearch.com:  What is the background for this study?  What are the main findings?

Response: Despite improvements in surgical techniques, local residual tumor micro infiltration and circulating tumor cells continue causing tumor recurrence after resection. 

Calcium carbonate nanoparticles could scavenge H+ in the surgical wound, reserving the immunosuppressive tumor microenvironment and promoting the antitumor immuneresponses. 

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