Gene Linked To X-linked Intellectual Disability Identified In Less Than A Day

MedicalResearch.com Interview with:
Daryl Armstrong Scott, M.D., Ph.D
Associate Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US

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

Response: This case started with a male child with intellectual disability, developmental delay, hypotonia, hypermobile joints and relative macrocephaly (large head size). Clinical testing showed that he carried a small deletion on chromosome Xp11.22. Since the deleted region had not been previously associated with human disease, the patient was referred to our clinic for additional testing. However, a more detailed analysis revealed that mice that were missing one of the genes located in the deletion interval, Maged1, had neurocognitive and neurobehavioral problems. This sparked additional inquiries which resulted in the identification of three other males from two other families who carried small, overlapping Xp11.22 deletions and had similar features. In all cases, their deletions were inherited from their asymptomatic mothers.

We concluded that deletion of an ~430 kb region on chromosome Xp11.22 that encompasses two pseudogenes (CENPVL1 and CENPVL2) and two protein-coding genes (MAGED1 and GSPT2) causes a novel, syndromic form of X-linked intellectual disability characterized by developmental delay, hypotonia, hypermobile joints and relative macrocephaly.

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Cooling System Can Prevent Hair Loss During Chemotherapy

MedicalResearch.com Interview with:

Julie Rani Nangia, M.D. Assistant Professor Breast Center - Clinic Baylor College of Medicine Houston, TX, US

Dr. Julie Nangia

Julie Rani Nangia, M.D.
Assistant Professor
Breast Center – Clinic
Baylor College of Medicine
Houston, TX, US

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

Response: This study was fueled by the feedback from women undergoing chemotherapy treatment for breast cancer. One of the most distressing side effects of their treatment is hair loss. It robs them of their anonymity and, for many, their femininity. Scalp cooling therapy has been available for a few years in the UK, but has faced obstacles in FDA clearance in the states. The makers of the scalp cooling device used in this study, Paxman Coolers Ltd., have a personal connection to breast cancer, as the company founder’s wife passed away from the disease.

This was the first randomized scalp cooling study, and it shows that the Paxman Hair Loss Prevention System is an effective therapy for reducing chemotherapy-induced alopecia. The results show a 50% increase in hair preservation of grade 0 or 1, meaning use of a scarf or wig is not necessary, in patients who received the scalp cooling therapy as opposed to those who did not.

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Maternal Mortality and Morbidity Increased on Weekends

MedicalResearch.com Interview with;
Dr. Amirhossein Moaddab
Postdoctoral Research Fellow at Baylor College of Medicine
Houston, Texas

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

Response: Based on data from the Centers for Disease Control and Prevention, the United States maternal mortality ratio is three to four times higher than that of most other developed nations. Previous studies from the demonstrated a possible association between weekend hospital admissions and higher rates of mortality and poor health outcomes.

We investigated differences in maternal and fetal death ratios on weekends compared to weekdays and during different months of the year. In addition we investigated the presence of any medical and obstetrics complications in women who gave birth to a live child and in their offspring by day of delivery.

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Improved Resolution of Disease Phenotypes With Multilocus Genomic Variation

MedicalResearch.com Interview with:
Jennifer E Posey MD, PhD

Assistant Professor
Department of Molecular and Human Genetics
Baylor College of Medicine

Tamar Harel MD, PhD
Clinical Genetics Academic Research Fellow
Department of Molecular and Human Genetics
Baylor College of Medicine

Current affiliation:
Department of Genetic and Metabolic Diseases
Hadassah-Hebrew University Medical Center
Jerusalem, Israel

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

Response: As physician scientists and geneticists, our goal is to understand how genetic variation in each of us can impact health and disease. Physicians are often taught that the simplest explanation for a medical condition is the most correct explanation, and have historically searched for a single unifying diagnosis. However, in our own practice, we have met – and learned from – individuals who have more than one genetic condition affecting their health.

In the past, it was difficult for physicians to diagnose such individuals. Genetic testing required a physician to recognize the potential for more than one genetic diagnosis in an individual. Single-gene and gene panel testing provided an additional barrier to accurate diagnoses, as they are more narrow in scope, and more than one molecular test was often needed to identify all conditions. Targeted testing also required a physician to accurately pre-suppose which combination of genetic conditions was most likely, and choose the correct targeted tests.

The clinical availability of whole exome sequencing (WES) has removed these barriers: WES is a broad-based, unbiased analysis of an individual’s genetic variation that does not pre-suppose a specific genetic cause. If analysis is pursued systematically, WES can identify more than one genetic diagnosis in an individual, even when not suspected.
In our study, we have been able to assess the frequency with which individuals can have more than one genetic diagnosis, and have begun to understand how genetic variation at more than one place in the genome can affect how a condition may present. We found that among 7,374 individuals referred for WES, 2,076 (28%) had a molecular diagnosis. Of these 2,076, 5% had two, three, or four molecular diagnoses. In our analyses of the clinical features that may be observed in an individual with two genetic conditions, we found that pairs of diagnoses with overlapping clinical features may be incompletely diagnosed as having one or the other condition, and pairs of diagnoses with very distinct clinical features may be erroneously diagnosed in the clinic as having an entirely new condition.
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Depressive disorders are the most frequent neuropsychiatric complication of TBI

MedicalResearch.com Interview with:

Ricardo E. Jorge MD Professor of Psychiatry and Behavioral Sciences Director Houston Translational Research Center for TBI and Stress Disorders Senior Scientist Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry Michael E DeBakey VA Medical Center Baylor College of Medicine

Dr. Ricardo Jorge

Ricardo E. Jorge  MD
Professor of Psychiatry and Behavioral Sciences
Director Houston Translational Research Center for TBI and Stress Disorders
Senior Scientist  Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry
Michael E DeBakey VA Medical Center
Baylor College of Medicine

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

Response: Depressive disorders affect between one-third and one-half of patients with traumatic brain injury. Once established, these disorders are difficult to treat and frequently follow a chronic and refractory course.

Depression has a deleterious effect on TBI outcomes, particularly affecting the community reintegration of TBI patients.

In this randomized clinical trial that included 94 adult patients with TBI, the hazards for developing depression for participants receiving placebo were about 4 times the hazards of participants receiving sertraline treatment.

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Brain RAP is a Critical Mediator of Leptin Resistance and Obesity

MedicalResearch.com Interview with:

Makoto Fukuda Ph.D. Assistant Professor Children's Nutrition Research Center Department of Pediatrics Baylor College of Medicine Houston, Texas 77030

Dr. Makoto Fukuda

Makoto Fukuda Ph.D.
Assistant Professor
Children’s Nutrition Research Center
Department of Pediatrics
Baylor College of Medicine
Houston, Texas 77030

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

Response: A hallmark characteristic of obesity is diminished actions of metabolic hormones that are critically required to maintain whole body energy balance and glucose homeostasis. Leptin is a crucial and powerful hormone that keeps body weight normal. It was hoped that leptin might be a “magic bullet” that could cure obesity. Shortly after the discovery, however, obese individuals were found to have little or no response to exogenously administered leptin, a state of “leptin resistance”. These observations created a central question to be addressed in the field, which would help our understanding of the core of pathophysiology of obesity. While we and other groups previously demonstrated that Epac, a signaling molecule known as a GTP/GDP exchange factor directly activated by cAMP, is involved in cellular leptin resistance, the role of brain Epac signaling in the whole body metabolism has not yet established.

We approached this question by using brain-specific knockout mice of Rap1, a direct activator of Epac. As expected from previous results, mice with brain-specific deficiency of Rap1 failed to develop leptin resistance even when they were challenged with a hypercaloric diet. What impressed us most in this study was that Rap1 in the brain plays a key role in the whole body metabolic control, beyond its role in controlling leptin sensitivity. Loss of brain Rap1 protects mice from diet-induced obesity and disordered glucose balance, whereas these knockout mice maintained a similar body weight to that of control mice on a normal regular diet. Further, pharmacological inhibition of this pathway reversed leptin resistance and reduced the body weight of dietary obese mice. At the cellular level, we found an unexpected link between Rap1 and endoplasmic reticulum (ER) stress that has emerged as a causative contributor to the development of leptin resistance.

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Sertraline May Prevent Depression Following Traumatic Brain Injury

MedicalResearch.com Interview with:

Ricardo E. Jorge MD Professor of Psychiatry and Behavioral Sciences Director Houston Translational Research Center for TBI and Stress Disorders Senior Scientist Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry Michael E DeBakey VA Medical Center Baylor College of Medicine

Dr. Ricardo Jorge

Ricardo E. Jorge MD
Professor of Psychiatry and Behavioral Sciences
Director Houston Translational Research Center for TBI and Stress Disorders
Senior Scientist Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry
Michael E DeBakey VA Medical Center
Baylor College of Medicine

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

Response: Depressive disorders affect between one-third and one-half of patients with traumatic brain injury (TBI). Once established, these disorders are difficult to treat and frequently follow a chronic and refractory course.

Depression has a deleterious effect on TBI outcomes, particularly affecting the community reintegration of TBI patients. In this randomized clinical trial that included 94 adult patients with TBI, the hazards for developing depression for participants receiving placebo were about 4 times the hazards of participants receiving sertraline treatment.

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Comparable Diabetes and Heart Disease Care Provided By Physicians and Advanced Care Providers

MedicalResearch.com Interview with:
Salim S. Virani, MD, PhD and
Julia Akeroyd MPH
Health Services Research and Development
Michael E. DeBakey Veterans Affairs Medical Center
Houston

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

Response: Given the increase in the number of Americans seeking primary health care due to the Affordable Care Act, combined with current and anticipated physician shortages in the US, there is a growing need to identify other models of primary care delivery to address chronic diseases.

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Baylor Scientists Grow Noroviruses In Lab For First Time

MedicalResearch.com Interview with:

Mary K. Estes, Ph.D. Distinguished Service Professor Cullen Endowed Chair of Human and Molecular Virology Department of Molecular Virology and Microbiology Baylor College of Medicine Houston, TX 77030

Dr. Mary Estes

Mary K. Estes, Ph.D.
Distinguished Service Professor
Cullen Endowed Chair of Human and Molecular Virology
Department of Molecular Virology and Microbiology
Baylor College of Medicine
Houston, TX 77030

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

Response: Noroviruses are the most common cause of acute gastroenteritis (vomiting and diarrhea) worldwide and the leading cause of food-borne gastroenteritis. They also can cause chronic (long-lasting) illness in immunocompromised patients. These viruses are highly contagious and spread rapidly among people. The first report of an outbreak caused by a norovirus was in an elementary school in Norwalk, Ohio in 1968. Since that time, it became known that the virus damaged cells in the small intestine of infected people but attempts by many research groups to grow human noroviruses in the laboratory in a variety of intestinal cancer cells lines failed. This inability to grow human norovirus has been considered the single greatest barrier to norovirus research because it limited studies to understand how the virus makes people sick and how to inactivate the virus to prevent infection.

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Testosterone Therapy Improved Sexual Function in Older Men

MedicalResearch.com Interview with:
Glenn Cunningham, MD
Departments of Medicine and Molecular and Cellular Biology
Division of Diabetes, Endocrinology and Metabolism
Baylor College of Medicine and Baylor St. Luke’s Medical Center
Houston, Texas 77030

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

Response: The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of testosterone in symptomatic men ≥65 years with unequivocally low testosterone levels. Previous studies in older men have been limited and the results have been conflicting. Initial results of the Sexual Function Trial showed that testosterone improved sexual activity, sexual desire and erectile function.

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Computerized Triggers May Help Prevent Delays in X-Ray Reports

MedicalResearch.com Interview with:

Daniel R. Murphy, M.D., M.B.A. Assistant Professor - Interim Director of GIM at Baylor Clinic Department of Medicine Health Svc Research & General Internal Medicine Baylor College of Medicine Houston, TX

Dr. Daniel Murphy

Daniel R. Murphy, M.D., M.B.A.
Assistant Professor – Interim Director of GIM at Baylor Clinic
Department of Medicine
Health Svc Research & General Internal Medicine
Baylor College of Medicine
Houston, TX

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

Dr. Murphy: Electronic health records (EHRs) have improved communication in health care, but they have not eliminated the problem of patients failing to receive appropriate and timely follow up after abnormal test results. For example, after a chest x-ray result where a radiologist identifies a potentially cancerous mass and suggests additional evaluation, about 8% of patients do not receive follow-up imaging or have a visit with an appropriate specialist within 30 days. Identifying patients experiencing a delay with traditional methods, like randomly reviewing charts, is not practical. Fortunately, EHRs collect large amounts of data each day that can be useful in automating the process of identifying such patients.

We evaluated whether an electronic “trigger” algorithm designed to detect delays in follow up of abnormal lung imaging tests could help medical facilities identify patients likely to have experienced a delay. Of 40,218 imaging tests performed, the trigger found 655 with a possible delay. Reviewing a subset of these records showed that 61% were truly delays in care that required action. We also found that the trigger had a sensitivity of 99%, indicating that it missed very few actual delays.

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Acid Suppression Reduces Risk of Esophageal Cancer in Barrett’s Esophagus

MedicalResearch.com Interview with:

Dr. Aaron Thrift

Dr. Aaron Thrift

Aaron Peter Thrift, Ph.D
Assistant Professor
Duncan Cancer Center
Department of Medicine, Gastroenterology Section
Baylor College of Medicine
Houston, TX, US

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

Dr. Thrift: Patients with Barrett’s esophagus are at significantly higher risk of developing esophageal adenocarcinoma. Due to the continued rise in incidence of esophageal adenocarcinoma attention has turned to chemoprevention as a method to delay or halt the progression of Barrett’s esophagus to neoplasia, including invasive cancer. Acid suppressive medications, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), are commonly used in patients with gastroesophageal reflux disease (GERD), the primary risk factor for Barrett’s esophagus.

We contacted a nested case-control study involving 311 patients with Barrett’s esophagus who developed esophageal adenocarcinoma (cases) and 856 matched controls (patients with Barrett’s esophagus but who did not develop esophageal adenocarcinoma). Compared to never users, we found that Barrett’s esophagus patients taking PPIs and H2RAs had 69% and 45% lower risk of esophageal adenocarcinoma, respectively. The associations were independent of other risk factors for progression, including concomitant use of nonsteroidal anti-inflammatory drugs and statins.
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