Common Antidepressant Sertraline Does Not Improve Depression in Chronic Kidney Disease Patients

MedicalResearch.com Interview with:

Dr. Susan Hedayati MD University of Texas Southwestern Dallas, Texas

Dr. Hedayati

Dr. Susan Hedayati MD
Yin Quan-Yuen Distinguished Professorship in Nephrology
University of Texas Southwestern
Dallas, Texas

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

Response: We previously showed that Major Depression is associated with a significantly higher risk of death, dialysis initiation, and hospitalization among patients with Chronic Kidney Disease (CKD). Now we show that a common antidepressant medication, a selective serotonin reuptake inhibitors (SSRI), sertraline, does not improve depression in this patient population, a chronically ill group that is not only at significantly increased risk for developing depression but also its serious complications.

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Serotonin Receptors Tied To Weight Gain From Atypical Antipsychotic Medications

MedicalResearch.com Interview with:

Chen Liu, Ph.D. Assistant Professor Departments of Internal Medicine and Neuroscience Division of Hypothalamic Research The University of Texas Southwestern Medical Center Dallas, Texas 75390-9077

Dr. Chen Liu

Chen Liu, Ph.D.
Assistant Professor
Departments of Internal Medicine and Neuroscience
Division of Hypothalamic Research
The University of Texas Southwestern Medical Center
Dallas, Texas 75390-9077 

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

Response: Atypical antipsychotics are second-generation antipsychotics (SGAs) that have been increasingly used to treat a variety of neuropsychiatric conditions such as schizophrenia, depression, and autism. Many patients taking these medications, however, are left in an agonizing dilemma.

On one hand, they rely on these drugs’ psychotropic effect for normal functioning in daily life. On the other, many SGAs, including the most widely prescribed olanzapine and clozapine, can cause a metabolic syndrome that is known for excessive weight gain, dyslipidemia, and type-2 diabetes_ENREF_2. Notably, while full-blown type 2 diabetes and morbid obesity typically take years to unfold in the general population, these conditions progress at a much faster pace (within months) following second-generation antipsychotics treatment. Other factors such as ethnicity, age, and sex can also aggravate SGA-induced metabolic syndrome. Together, these peculiar features strongly suggest a distinct etiology underlying SGA-induced metabolic syndrome that has yet been fully elucidated. Currently, there is no medication specifically targeting SGA-induced metabolic syndrome. For many youths and adults taking second-generation antipsychotics, metabolic complications are difficult to manage as lifestyle changes, nutritional consulting, and commonly used anti-diabetic medications only provide limited relief.

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Oral Treatment Option for RA Includes Tofacitinib (XELJANZ®) Plus Methotrexate

MedicalResearch.com Interview with:

Roy Fleischmann, MD MACR Medical Director Metroplex Clinical Research Center Clinical Professor of Medicine University of Texas Southwestern Medical Center Dallas, TX 75231

Dr. Fleischmann

Roy Fleischmann, MD MACR
Medical Director
Metroplex Clinical Research Center
Clinical Professor of Medicine
University of Texas Southwestern Medical Center
Dallas, TX 75231

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

Response: In the phase 3 studies of tofacitinib, it was noted that the clinical responses to tofacitinib monotherapy were higher than the responses to tofaciotinib plus MTX and that tofacitinib plus methotrexate had numerically higher clinical responses compared to adalimumab plus methotrexate. This study was a non-inferiority design which compared tofacitinib monotherapy to tofacitinib + MTX and to adalimumab +MTX and tofacitinib monotherapy to tofacitinib +MTX in MTX incomplete responders. It was found that tofacitinib + MTX is non-inferior to adalimumab + MTX (and vice versa) and neither was superior to the other. The results of tofacitinib to either combination was non-conclusive showing neither non-inferiority or inferiority, but suggesting that either combination will be effective in more patients in a group of patients.

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Study Suggests Isolated Systolic Hypertension In Young Adults Should Be Treated To Prevent Damage To Aorta

MedicalResearch.com Interview with:

Wanpen Vongpatanasin, M.D.</strong> Professor of Medicine Norman & Audrey Kaplan Chair in Hypertension Fredric L. Coe Professorship in Nephrolithiasis and Mineral Metabolism Research Director, Hypertension Section, Cardiology Division, UT Southwestern Medical Center Dallas, TX 75390-8586

Dr. Vongpatanasin

Wanpen Vongpatanasin, M.D.
Professor of Medicine
Norman & Audrey Kaplan Chair in Hypertension
Fredric L. Coe Professorship in Nephrolithiasis and Mineral Metabolism Research
Director, Hypertension Section,
Cardiology Division,
UT Southwestern Medical Center
Dallas, TX 75390-8586

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

Response: It is well know that treatment of isolated systolic hypertension (ISH), a subtype of hypertension with elevated systolic BP 140 or above but normal diastolic BP of < 90 mmHg, improves cardiovascular outcomes in older adults after the sixth decade of life. However, it is controversial if ISH in young adults requires treatment because it was suggested that elevated systolic BP in these individuals are related to high stroke volume, rather than increased aortic stiffness. In earlier case series, ISH in young adults were particularly common in athletes with long arms and legs, suggesting that pulse wave amplification coupled with high stroke volume were responsible for elevated brachial systolic blood pressure but the true central BP was normal. Thus,  isolated systolic hypertension was proposed to be a spurious condition in young adults that can be ignored.

However, previous studies used only indirect technique in assessing aortic structure and function. Furthermore, none of these studies were conducted in the U.S. Population.

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Statins Users May Have Higher Likelihood of Back Disorders

MedicalResearch.com Interview with:

Una Makris MD, MSc Clinical Investigator at the VA North Texas Health System Assistant Professor at UT Southwestern Medical Center Departments on Internal Medicine and Clinical Sciences

Dr. Makris

Una Makris MD, MSc
Clinical Investigator at the VA North Texas Health System
VA North Texas Health Care System
Assistant Professor at UT Southwestern Medical Center
Departments on Internal Medicine and Clinical Sciences
Dr. Makris is a Rheumatologist, clinically, and spends the majority of time focused on clinical research investigating how to improve outcomes for adults with back pain.

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

Response: Back pain is the most common type of musculoskeletal (MSK) pain. We know that expenditures for back pain exceed $100 billion each year (and this was in 2005). Back pain results in tremendous disability (including reduced mobility) and impaired quality of life (not exclusive to physical consequences, but also including important psychosocial repercussions). We also know that statins are prescribed very often, and frequently in younger populations who are active. Some reports suggest that statins may have a protective effect on  musculoskeletal conditions such as back pain.

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Adiposity Related Cancer Risk May Vary On Fat Locations

MedicalResearch.com Interview with:
Arjun Gupta, MD and

Ian J. Neeland MD, Assistant Professor
Dedman Family Scholar in Clinical Care
Division of Cardiology
UT Southwestern Medical Center

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

Response: Adiposity is traditionally measured using the body mass index, which refers to a persons weight in kilograms divided by their height (in meters) squared. Persons with higher body mas index have been shown to have increased risk of certain cancers, however body mass index by itself is not a completely representative measure of body fat risk, because distinct fat depots such as visceral adipose tissue, abdominal subcutaneous adipose tissue, liver fat and lower body fat have differing metabolic impact.

We aimed to study the relationship between specific fat depots and the risk of incident cancer among relatively young, multiethnic participants in the Dallas Heart Study. Individuals without prevalent cancer underwent quantification of adipose depots using MRI and DEXA scans from 2000-2002, and were followed for the development of cancer for up to 12 years. In multivariable models adjusted for age, sex, race, smoking, alcohol use, family history of malignancy and body mass index, visceral adipose tissue, subcutaneous adipose tissue or liver fat were not associated with risk of cancer but each 1-standard deviation increase in lower body fat was associated with a 31% reduced incidence of cancer.

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Obstructive Sleep Apnea More Common In Obese Adolescents With Enlarged Tonsils

MedicalResearch.com Interview with:

Ron B. Mitchell, MD Professor and Vice Chairman, Department of Otolaryngology, Head and Neck Surgery William Beckner Distinguished Chair in Otolaryngology Chief of Pediatric Otolaryngology UT Southwestern and Children's Medical Center Dallas Dallas, TX 75207

Dr. Ron Mitchell

Ron B. Mitchell, MD
Professor and Vice Chairman,
Department of Otolaryngology, Head and Neck Surgery
William Beckner Distinguished Chair in Otolaryngology
Chief of Pediatric Otolaryngology
UT Southwestern and Children’s Medical Center Dallas
Dallas, TX 75207

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

Response: Obstructive Sleep Apnea (OSA) has not been widely studies in adolescents. This is one of a few studies that was targeted at 12-17 year olds who were referred for a sleep study for possible OSA. The study included 224 adolescents (53% male). aged 12 to 17 years. The mean BMI was 33.4 and most were either Hispanic or African American (85.3%). A total of 148 (66.1%) were obese. Most adolescents referred for a sleep study (68%), had  Obstructive Sleep Apnea. Normal-weight adolescents were least likely to have OSA at 48%, while obese children were most likely at 77%. Severe OSA was most likely in obese males with tonsillar hypertrophy.

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Study Fails To Support Routine Screening For Subclinical Hypothyroidism During Pregnancy

MedicalResearch.com Interview with:

Professor, Brian Casey, M.D. Gillette Professorship of Obstetrics and Gynecology UT Southwestern Medical Center

Dr. Casey

Professor Brian Casey, M.D.
Gillette Professorship of Obstetrics and Gynecology
UT Southwestern Medical Center 

MedicalResearch.com: What is the background for this study?
Response: For several decades now, subclinical thyroid disease, variously defined, has been associated with adverse pregnancy outcomes.  In 1999, two studies are responsible for increasing interest in subclinical thyroid disease during pregnancy because it was associated with impaired neuropsychological development in the fetus.  One study showed that children born to women with the highest TSH levels had lower IQ levels.  The other showed that children of women with isolated low free thyroid hormone levels performed worse on early psychomotor developmental tests. Together, these findings led several experts and professional organizations to recommend routine screening for and treatment of subclinical thyroid disease during pregnancy.

Our study was designed to determine whether screening for either of these two diagnoses and treatment with thyroid hormone replacement during pregnancy actually improved IQ in children at 5 years of age.

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Anti-Cancer Agent May Have Simultaneous Regenerative Properties

MedicalResearch.com Interview with:

Lawrence Lum, Ph.D. Associate Professor Virginia Murchison Linthicum Scholar in Medical Research UT Southwestern Medical Center

Dr. Lum

Lawrence Lum, Ph.D.
Associate Professor
Virginia Murchison Linthicum Scholar in Medical Research
UT Southwestern Medical Center

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

Response: Scarring of the adult heart due to excessive fibrotic responses is common after a heart attack, or following radiation therapy for the treatment of certain cancers. We have identified an anti-cancer agent currently in clinical development called WNT-974 that decreases fibrotic responses and improves heart function following myocardial infarction in mice. This unexpected observation was the outcome of a study focused on identifying unwanted adult tissue toxicities associated with this class of chemicals.

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Two Polyomaviruses Linked To Dermatoses in Immunocompromised Patients

MedicalResearch.com Interview with:

Richard Wang, M.D., Ph.D. Assistant Professor UT Southwestern Medical Center

Dr. Wang

Richard Wang, M.D., Ph.D.
Assistant Professor
UT Southwestern Medical Center

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

Response:

Currently, there are 13 polyomaviruses known to infect humans. Several members of this family of double-stranded DNA viruses—including Merkel Cell Polyomavirus, Trichodysplasia Spinulosa Polyomavirus, Human Polyomavirus 6 (HPyV6), and Human Polyomavirus 7 (HPyV7)—can be shed from skin of healthy individuals. While most polyomavirus infections are common and subclinical, several polyomaviruses have been associated with debilitating diseases in immunocompromised individuals. Most recently, HPyV7 was discovered in a pruritic and dyskeratotic eruption in two immunosuppressed transplant patients. A closely related polyomavirus, Human Polyomavirus 6, has not yet been strongly linked to any infectious diseases. Using the previously described, characteristic histologic pattern, we identify 3 additional cases of skin eruptions associated with infections of HPyV6 and HPyV7. The association of the dermatoses with highly active infections were confirmed through electron microscopy, immunohistochemistry, quantitative PCR, and complete sequencing. HPyV7 infects keratinocytes and affects their normal differentiation. In addition, next generation sequencing revealed that HPyV6 could persist in a latent state in the skin of a previously infected patient.

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Intermittent Fasting Inhibits Cancer Cells in Childhood Leukemia ALL

MedicalResearch.com Interview with:

Chengcheng (Alec) Zhang, Ph.D. Associate Professor Hortense L. and Morton H. Sanger Professorship in Oncology Michael L. Rosenberg Scholar for Medical Research Department of Physiology  UT Southwestern Medical Center

Dr. Alec Zhang

Chengcheng (Alec) Zhang, Ph.D.
Associate Professor
Hortense L. and Morton H. Sanger Professorship in Oncology
Michael L. Rosenberg Scholar for Medical Research
Department of Physiology
UT Southwestern Medical Center

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

Response: New therapeutic targets and approaches are needed to effectively treat leukemia. Acute myeloid leukemia (AML) is the most common form of adult acute leukemia whereas acute lymphoblastic leukemia (ALL) is the most common form of cancer in children; ALL also occurs in adults. Although treatment of pediatric ALL is highly effective, a sizeable number of patients are non-responders who succumb to this disease. The outcome of ALL in adults is significantly worse than for pediatric ALL. Additionally, some types of ALL have a much poorer prognosis than others.

Dietary restriction, including fasting, delays aging and has prolonged effects in a wide range of organisms and has been considered for cancer prevention. In certain types of solid tumor,_ENREF_1 dietary restriction regimens are able to promote T cell-mediated tumor cytotoxicity and enhance anticancer immunosurveillance, and coordinate with chemotherapy to promote the anti-cancer effects. However, the responsiveness of hematopoietic malignancies to dietary restriction, including fasting, remains unknown. Furthermore, whether dietary restriction alone can inhibit cancer development is not clear.

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Teledermatology Can Triage Many Post-Operative Skin Surgery Concerns

MedicalResearch.com Interview with:

Rajiv Nijhawan MD Department of Dermatology The University of Texas Southwestern Medical Center Dallas

Dr. Rajiv Nijhawan

Rajiv Nijhawan MD
Department of Dermatology
The University of Texas Southwestern Medical Center
Dallas

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

Response: From a healthcare perspective, we are constantly working to improve access to patients, and telemedicine has proved to be an excellent platform for this goal especially in the field of dermatology. In regards to surgical dermatology, the role of telemedicine has been limited. The ubiquity of smartphones with photograph capability has provided an opportunity for patients to take self-acquired photographs (selfies) easily. Our experience has been that few patients who call with post-operative concerns have major issues (e.g. infection, bleeding, etc.) while the majority of concerns are minor in nature, and patients are often seeking reassurance.

Our study shows that the majority of concerns can easily be triaged and managed through patient-directed photography without burdening the patient to take time off work for another appointment, find transportation/travel (many of our patients travel hours for their visits), wait to see the provider, etc. This option of triaging a post-operative concern essentially immediately through the use of patient-directed photographs provides the opportunity for immediate feedback on the patient’s concerns and likely reduces anxiety while making the process as patient-centered as possible. In addition, it allows the physician to be as efficient as possible by not having to overbook his/her schedule to accommodate these often non-urgent concerns.

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Delayed Epinephrine Linked To Worse Survival From In-Patient Cardiac Arrest

MedicalResearch.com Interview with:
Rohan Khera, MD

Cardiology Fellow, T32 Clinical-Investigator Pathway
UT Southwestern Medical Center
Dallas, TX

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

Response: Nearly 200 thousand people have an in-hospital cardiac arrest in the US each year. Of these, the vast majority have a non-shockable initial rhythm – either pulseless electric activity (PEA) or asystole. The survival of this type of arrest remains poor at around 12-14%. Moreover, even after accounting for differences in case mix, there is a wide variation in survival across hospitals – and this serves as a potential avenue for targeting quality improvement strategies at poor performing hospitals.

Recent data suggest that a shorter time from the onset of cardiac arrest to the first dose of epinephrine is independently associated with higher survival. Against this background of wide hospital variation in cardiac arrest survival, and patient-level data suggesting an association between time to epinephrine and patient survival, we wanted to assess (A) if there were differences in time to epinephrine administration across hospitals, and (B) if a hospital’s rate of timely epinephrine use was associated with its cardiac arrest survival rate. Within Get With The Guidelines-Resuscitation, we identified nearly 104-thousand adult patients at 548 hospitals with an in-hospital cardiac arrest attributable to a non-shockable rhythms. delays to epinephrine,

We found that (a) proportion of cardiac arrests with delayed epinephrine markedly across hospitals, ranging from no arrests with delay (or 0%) to more than half of arrests at a hospital (54%).

There was an inverse correlation between a hospital’s rate of delayed epinephrine administration and its risk-standardized rate of survival to discharge and survival with functional recovery – compared to a low-performing hospitals, survival and recovery was 20% higher at hospitals that performed best on timely epinephrine use.

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Precise Structure of Cannabis Brain Receptor Defined

MedicalResearch.com Interview with:

(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum

(l-r) Dr. Zhenhua Shao and Dr. Daniel Rosenbaum UT Southwestern

Dan Rosenbaum, Ph.D.
Principal Investigator
Department of Biophysics
The University of Texas Southwestern Medical Center
Dallas, Texas

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

Response: This study focuses on the structure of the human CB1 cannabinoid receptor.

The CB1 protein is a membrane-embedded G protein-coupled receptor (GPCR) in the brain and peripheral tissues that responds to a variety of different compounds, including endogenous lipid messengers (‘endocannabinoids’), plant natural products (such as THC from the Cannabis sativa plant i.e. marijuana), and synthetic antagonists (such as the taranabant ligand used for this study). The CB1 receptor is involved in regulating neurotransmission in vertebrates, and is a potential therapeutic target for numerous conditions including obesity, pain, and epilepsy.

The main findings of this study entailed the solution of the high-resolution crystal structure of human CB1 receptor bound to the inhibitor taranabant. This structure revealed the precise shape of the inhibitor binding pocket, which is also responsible for binding THC and endocannabinoids. In addition to helping explain the mechanism of inhibitor and THC binding, our structure provides a framework for computational studies of binding to a large diversity of cannabinoid modulators of therapeutic importance.

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Increased Aortic Stiffness May Explain Elevated Hypertension Risk in African Americans

MedicalResearch.com Interview with:

Wanpen Vongpatanasin, M.D. Professor of Medicine Norman & Audrey Kaplan Chair in Hypertension Fredric L. Coe Professorship in Nephrolithiasis and Mineral Metabolism Research Director, Hypertension Section, Cardiology Division, UT Southwestern Medical Center Dallas, TX 75390-8586

Dr. Wanpen Vongpatanasin

Wanpen Vongpatanasin, M.D.
Professor of Medicine
Norman & Audrey Kaplan Chair in Hypertension
Fredric L. Coe Professorship in Nephrolithiasis and Mineral Metabolism Research
Director, Hypertension Section,
Cardiology Division,
UT Southwestern Medical Center
Dallas, TX 75390-8586

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

Response: Aortic stiffness is known to be associated with cardiovascular disease, including heart attack, stroke, and heart failure, possibly related to increase afterload to the left ventricle. Previous studies have not directly assessed proximal aortic function among ethnic minorities in the United States. We evaluated the multiethnic, population-based Dallas Heart Study participants (N=2544, 54.2% women, 49.7% Black) who underwent cardiovascular magnetic resonance imaging (CMR) at 1.5 Tesla. Aortic stiffness and characteristic impedance (Zc) were determined from aortic arch PWV and lumen area measurements. Linear regression was used to evaluate ethnic differences in proximal aortic wall stiffness using aortic arch PWV and Zc as dependent variables with and without adjustment for traditional cardiovascular risk factors.

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Little Change in PSA Use After Taskforce Recommendation

MedicalResearch.com Interview with:
Dr Ryan Hutchinson MD and
Yair Lotan MD

Department of Urology
University of Texas Southwestern Medical Center

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

Response: The United States Preventative Services Task Force recommendation against PSA screening generated significant controversy. Research since then has relied heavily on survey data to examine the impact of the recommendation on PSA screening practices. In a hotly charged issue such as this, such data can carry significant bias.

We examined a large, whole-institution data in the years before and after the USPSTF recommendations reflecting actual practice and found that the changes in PSA use at our institution, if any, were small. This is more consistent with behavior seen after the vast majority of practice recommendations.

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Genetic Ancestry using Mitochondrial DNA in patients with Triple-Negative Breast Cancer

MedicalResearch.com Interview with:

Roshni Rao, M.D Breast Surgery University of Texas Southwestern

Dr. Roshni Rao

Roshni Rao, M.D
Breast Surgery
University of Texas Southwestern

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

Response: Triple negative breast cancer (TNBC) is characterized by not having estrogen, progesterone, or Her2Neu receptors. Although a less common type, it is aggressive, and leads to a disproportionate number of deaths from breast cancer.

TNBC is more common in young, African American women, but can be found in other ethnic groups as well.

This study performed mitochondrial DNA (mtDNA) analysis, to evaluate for patient genetic ancestry, in 92 patients with TNBC. In regards to self-identified ethnicity, there were 31 African-Americans, 31 Whites, and 30 Hispanics. Utilizing mtDNA, 13% of patients had discordance between self identified ethnicity and mtDNA analysis. Discordance was highest in the Hispanic group. The Hispanic patients were also much younger at initial age of diagnosis, and less likely to have a family history of breast cancer. Ancestry from Nigeria, Cameroon, or Sierre Leone were most common in the African-Americans with triple negative breast cancer.

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High Phosphates in Processed Foods May Contribute To Increased Blood Pressure

MedicalResearch.com Interview with:

Dr-Wanpen-Vongpatanasin.jpg

Dr. Vongpatanasin

Wanpen Vongpatanasin, MD
Professor of Medicine
Norman & Audrey Kaplan Chair in Hypertension Research
Director, Hypertension Section
Cardiology Division
UT Southwestern Medical Center

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

Response: Inorganic phosphate has been added to our processed food at an enormous amount as food preservatives and flavor enhancer such that typical American diet contains twice as much as the recommended daily allowance. A high phosphate (Pi) diet was recently shown to trigger blood pressure (BP) elevation in otherwise normal rats but the mechanisms are still unknown.We found that rats treated with high phosphate diet that mimics the excess Pi consumed by the general American population developed high BP related to increased sympathetic nerve activity (SNA), resulting in excessive peripheral vasoconstriction. This exaggerated increase in SNA and BP is evident particularly during exercise. This study is conducted in collaboration with Drs. Masaki Mizuno and Scott Smith, the two leading experts in neural control of circulation at UT Southwestern in the Department of Health Care Sciences.

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Study Detects Mechanism That Keeps Insulin Receptors on Cell Surface

MedicalResearch.com Interview with:
Dr. Eunhee Choi
Research scientist in the Yu laboratory and lead author of the study
UT SouthWestern
Dr. Hongtao Yu, Professor of Pharmacology at UT Southwestern and
Investigator with the Howard Hughes Medical Institute (HHMI).

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

Response: Diabetes is a metabolic disease. High blood sugar is a common symptom of diabetes, and over time it can lead to serious damage to multiple organs. Insulin, a hormone made by the pancreas, regulates blood sugar. Diabetes can occur either when the pancreas does not produce enough insulin (type 1 diabetes) or when the cells in our body cannot efficiently respond to insulin (type 2 diabetes). Diabetes is now a major global epidemic. The World Health Organization (WHO) estimates that more than 400 million people worldwide have diabetes.

Insulin binds the insulin receptor (IR) at the cell surface. The insulin-bound IR can send signals inside the cell and instruct the cell to take up sugar from the blood, thus maintaining healthy blood sugar levels. After insulin has done its job, insulin-bound IR is packaged into small vesicles with a protein coat and dragged into the cell, thus terminating the signals. An adequate level of IR on the cell surface is crucial for insulin signaling and blood sugar metabolism. We have found a new mechanism that keeps IR at the cell surface. Without such a mechanism, IR is prematurely dragged inside the cell before it encounters insulin.

Our discovery is quite unexpected. A main interest of our lab is to study the molecular control of cell division. During each cell division, the duplicated sister chromosomes are evenly separated into two daughter cells. A cellular surveillance system called the spindle checkpoint ensures the accuracy of sister-chromosome separation. Three checkpoint proteins, p31comet, MAD2 and BUBR1, are critical for accurate chromosome segregation. In the process of studying this checkpoint, we have unexpectedly discovered that mice lacking p31comet in the liver develop diabetes. Liver cells lacking p31comet do not have IR on the cell surface, and thus cannot respond to insulin. We have further shown that MAD2 directly binds to IR, and along with BUBR1, helps to drag IR inside the cell. p31comet prevents BUBR1 from interacting with IR-bound MAD2, thus keeping IR at the cell surface. In cells lacking p31comet, MAD2 and BUBR1 gain the upper hand and remove IR from the cell surface. Thus, the dynamic tug-of-war between p31comet and MAD2-BUBR1 determines the status of IR at the cell surface.

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Potassium Compound In Fruits/Vegetables May Reduce Oxidative Stress

MedicalResearch.com Interview with:

Dr-Wanpen-Vongpatanasin.jpg

Dr. Vongpatanasin

Dr. Wanpen Vongpatanasin MD
The Norman and Audrey Kaplan Chair in Hypertension
UT Southwestern Medical Center

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

Response: Diet rich in fruits, vegetables, and dairy products, known as the DASH diet, is known to reduce blood pressure in hypertensive patients. More recently, the DASH diet was shown to reduce oxidative stress in people with and without high blood pressure . However, the main nutritional ingredient responsible for these beneficial effects of the DASH diet remain unknown. Because the DASH diet is rich in potassium (K), magnesium (Mg), and alkali, we performed a randomized, double-blinded, placebo-controlled study to compare effects of KMg Citrate (KMgCit), K Chloride (KCl), and K Citrate (KCit) to allow dissociation of the three in hypertensive and prehypertensive individuals. This study was conducted in collaboration with Drs. Charles Pak and Orson Moe at UT Southwestern, the two leading experts in the field of Mineral Metabolism. We found that oxidative stress was markedly reduced by KMgCit powder compared to placebo, K Chloride, and K Citrate. On the hand, KMgCit has no significant effects on blood pressure .

MedicalResearch.com Editor’s note:  DO NOT Take Potassium supplements unless under the direction of your health care provider.

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Two Kinases That Keep Heart Beating May Be Targets For Heart Failure Therapy

Dr-Audrey-Chang credit: UT Southwestern

Dr. Audrey Chang

MedicalResearch.com Interview with:
Dr. Audrey Chang, PhD
Kamm-Stull Lab
UT Southwestern Medical Center
AudreyN.Chang@UTSouthwestern.edu

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

Response: The heart is a singular kind of muscle that contracts and relaxes continuously over a lifetime to pump blood to the body’s organs. Contractions depend on a motor protein myosin pulling on actin filaments in specialized structures. Heart contraction is improved when myosin has a phosphate molecule attached to it (phosphorylation), and a constant amount of phosphorylation is essential for normal heart function. The amount of phosphorylation necessary for optimal cardiac performance is maintained by a balance in the activities of myosin kinase enzymes that add the phosphate and an opposing phosphatase enzyme that removes the phosphate. If the amount of phosphorylation is too low, heart failure results. Animal models with increased myosin phosphorylation have enhanced cardiac performance that resist stresses that cause heart failure.

In this recent study reported in PNAS, a new kinase that phosphorylates myosin in heart muscle, MLCK4, was discovered and its crystal structure reported, a first for any myosin kinase family member. Compared to distinct myosin kinases in other kinds of muscles (skeletal and smooth), this cardiac-specific kinase lacks a conserved regulatory segment that inhibits kinase activity consistent with biochemical studies that it is always turned on. Additionally, another related myosin kinase found only in heart muscle (MLCK3) contains a modified regulatory segment, allowing partial activity enhanced by the calcium modulator protein, calmodulin. Thus, both myosin kinases unique to cardiac muscle provide phosphate to myosin in normal beating hearts to optimize performance and prevent heart failure induced by stresses.

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Hospitals In Better Financial Shape Do Not Necessarily Have Better Outcomes

MedicalResearch.com Interview with:
Oanh Kieu Nguyen, MD, MAS | Assistant Professor UT Southwestern Medical Center Divisions of General Internal Medicine and Outcomes and Health Services Research Dallas, TXOanh Kieu Nguyen, MD, MAS | Assistant Professor
UT Southwestern Medical Center
Divisions of General Internal Medicine and Outcomes and Health Services Research
Dallas, TX

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

Dr. Nguyen: The impetus for this study was Steven Brill’s 2013 Time magazine award-winning article, “Bitter Pill: Why Medical Bills Are Killing Us.” This report investigated inflated charges for hospital bills, and and suggested that a major driver of irrationally high charges was the disproportionate negotiating power of hospitals, as evidenced through their high profit margins. As hospital physicians, our reaction was “But what if hospitals that make more money are delivering more value and better outcomes to patients? If that’s the case, wouldn’t most people say that their profits justifiably earned?” Surprisingly, we found that no one had really looked at this issue in a systematic way.

We set out to answer this question using hospital financial data from California’s Office of Statewide Health Planning and Development (OSHPD) and outcomes data on 30-day readmissions and mortality for congestive heart failure, acute myocardial infarction (‘heart attacks’), and pneumonia from the Centers for Medicare and Medicaid Services (CMS) Hospital Compare website. California has more hospitals than any other state other than Texas, and also has a wide diversity of hospital types. The OSHPD financial data are also audited, so we thought these would be more reliable than using data from other sources. Because the outcomes reported on Hospital Compare are viewable by the general public, we thought hospitals would be most motivated to target improvements in these outcomes.

We found that there was almost no association between how much money a hospital made and its subsequent performance on outcomes. The exception to this was we found that hospitals that had better finances reported higher rates of 30-day mortality for congestive heart failure, which was counterintuitive. We’re not sure why this was the case but speculate that it is possible that hospitals with better finances take care of sicker heart failure patients because they have more advanced (and more expensive) treatments available.

Additionally, we looked to see if hospitals with lower readmissions rates subsequently made less money. This is a specific area of policy concern given federal penalties in the U.S. for excessive hospital readmissions. Many critics of these penalties have argued that reducing readmissions makes no financial sense for hospitals, since readmissions still generate hospital revenue despite the penalties. Thus, reducing readmissions would reduce a key source of hospital revenue and lead to poorer hospital finances. However, our analysis showed that lower readmissions rates were not associated with poorer hospital finances, as has been feared.  Continue reading

CRISPR Successfully Restores Gene Function in Animal Model of Duchenne Muscular Dystrophy

MedicalResearch.com Interview with:
Rhonda Bassel-Duby, Ph.D. and

Dr. Chengzu Long, PhD
Department of Molecular Biology
UT Southwestern Medical Center
Dallas, TX 75390-9148

Medical Research: What is the background for this study? What are the main findings?

Response: Duchenne muscular dystrophy (DMD), which was first described by Duchenne de Boulogne (1806-1875) in 1860s, is one of the most severe and common type of muscular dystrophy. DMD is caused by mutations in the gene for dystrophin (DMD) on the X chromosome and affects approximately 1 in 3500 to 5000 boys. Without dystrophin, a large cytoskeletal protein, muscles degenerate, causing myopathy. Symptoms can be visible between 1 to 6 years old. Most Duchenne muscular dystrophy patients are confined to a wheelchair by age 12. Death of DMD patients usually occurs by age 25, typically from breathing complications and cardiomyopathy. Hence, therapy for  Duchenne muscular dystrophy necessitates sustained rescue of skeletal, respiratory and cardiac muscle structure and function. Although several gene therapies have been tested, there is no curative treatment so far.

Duchenne muscular dystrophy arises from a monogenic mutations in dystrophin gene. This makes DMD an ideal disease model for CRISPR-mediated gene editing therapeutics, a major breakthrough in gene engineering in the past three years. This system can remove the defect within the gene.

In 2014, in a first proof of concept study, Olson’s team used CRISPR-mediated gene editing to correct the dystrophin gene mutation in the germline of DMD mouse model. In this new paper, we advanced the same technology to postnatal muscle tissues by delivery gene editing components via a harmless adeno-associated virus. Skeletal and cardiac muscle showed progressive rescue of dystrophin protein.

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PA Catheterization Use Increases in CHF Without Shock or Respiratory Failure

Ambarish Pandey M.D. Division of Cardiology University of Texas Southwestern Medical Center Dallas, TX

Dr. Ambarish Pandey

Ambarish 

MedicalResearch.com Interview with:
Ambarish Pandey M.D.

Division of Cardiology
University of Texas Southwestern Medical Center
Dallas, TX

Medical Research: What is the background for this study? What are the main findings?

Dr. Pandey: Pulmonary artery (PA) catheters have been used for invasive bedside hemodynamic monitoring for past four decades. The ESCAPE trial, published in October 2005, demonstrated that use of  Pulmonary Artery catheter was not associated with a significant improvement in clinical outcomes of patients with heart failure. Accordingly, the current ACC/AHA guidelines discourage the routine use of PA catheter for routine management of acute heart failure in absence of cardiogenic shock or respiratory failure (Class III). Despite the significant evolution of available evidence base and guideline recommendations regarding use of  Pulmonary Artery catheters, national patterns of PA catheter utilization in hospitalized heart failure patients remain unknown.

In this study, we observed that use of PA catheter among patients with heart failure decline significantly in the Pre-ESCAPE era (2001 – 2006) followed by a consistent increase in its use in the Post-ESCAPE era (2007-2012). We also observed that the increase in use of  Pulmonary Artery catheters is most significant among heart failure patients without underlying cardiogenic shock or respiratory failure.

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PD-1 Blocker Extends Lives in Lung Cancer Patients

David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TXMedicalResearch.com Interview with:
David E. Gerber, MD

Associate Professor
Division of Hematology-Oncology
Associate Director for Clinical Research
Co-Leader, Experimental Therapeutics Program
Co-Director, Lung Disease Oriented Team
Harold C. Simmons Cancer Center
University of Texas Southwestern Medical Center
Dallas, TX

Medical Research: What is the background for this study? What are the main findings?

Dr. Gerber: In this trial, we compared an immunotherapy and a chemotherapy drug in patients with non-squamous non-small cell lung cancer (NSCLC) whose disease continued to progress after first-line chemotherapy. We found that nivolumab immunotherapy improved overall survival compared to docetaxel chemotherapy and was generally well tolerated. These results are significant because options for patients whose lung cancer progresses after initial treatment are limited.

Nivolumab is an immunotherapy drug that works by inhibiting the cellular pathway known as PD-1 protein on cells that block the body’s immune system from attacking cancerous cells.  The idea behind nivolumab and other immunotherapy drugs is to kick-start the body’s natural immune response to a cancer. Cancer develops and grows in part because it has put the brakes on the immune response. These drugs take the foot off the brake, allowing the immune system to accelerate and attack the cancer.

The phase 3 clinical trial followed more than 500 patients who had non-squamous non-small cell lung cancer (NSCLC): 287 received nivolumab and 268 received the chemotherapy drug docetaxel. The one-year survival rate was 51 percent in the nivolumab arm versus 39 percent in the docetaxel arm. The most common reported side effects with nivolumab were fatigue, nausea, decreased appetite, and weakness, and they were less severe than with docetaxel treatment. In a minority of cases, patients treated with nivolumab also developed autoimmune toxicities affecting various organs.

In addition to studying safety and efficacy, the trial examined the protein biomarker PD-L1, which is believed to play a role in suppressing the immune system. The study results suggested that patients with a higher level of PD-L1 in their cancers may experience the greatest benefit from nivolumab, which targets the related molecule PD1. Using a biomarker helps oncologists predict which patients will do best on which treatment, and plan their treatment accordingly. Other promising predictive biomarkers for cancer immunotherapies include the degree of immune cell infiltration within a tumor and the number of mutations a tumor has.

Specifically, the more mutations a cancer has, the more foreign it appears to the body, thus marking it for immune attack. With lung cancer, we see the greatest number of tumor mutations – and perhaps the greatest benefit from immunotherapy – among individuals with the heaviest smoking history.

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Heart Failure Risk Reduced With Increased Physical Activity

Ambarish Pandey, MD Cardiology Fellow, PGY5 University of Texas Southwestern Medical Center, Dallas, Texas 75390MedicalResearch.com Interview with:
Ambarish Pandey, MD

Cardiology Fellow, PGY5
University of Texas Southwestern Medical Center,
Dallas, Texas 75390

Medical Research: What is the background for this study? What are the main findings?

Dr. Berry: Physical inactivity is considered a major modifiable risk factor for coronary artery disease and the current guidelines recommend atleast 150 min/week (~ 500 MET-min/week) of moderate intensity physical activity to reduce the burden of coronary artery disease. In contrast, the role of physical activity in reducing risk of heart failure is not emphasized in the current guidelines. This is particularly relevant considering the increasing burden of heart failure in the community. Against this background, we performed this study to the dose-response relationship between physical activity levels and risk of heart failure.

We observed a dose dependent inverse association between physical activity levels and heart failure risk. Furthermore, we observed that the current guideline recommended physical activity levels (500 MET-min/week) are associated with only modest reduction in HF risk (< 10%). In contrast, a substantial reduction in heart failure risk was observed at twice and four times the recommended physical activity levels (19% and 35% risk reduction respectively)

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NFL Players: Concussions With Loss Of Consciousness Linked To Later Memory Problems and Brain Changes

C. Munro Cullum, PhD, ABPP Professor of Psychiatry and Neurology & Neurotherapeutics Pamela Blumenthal Distinguished Professor of Clinical Psychology Chief of Psychology Director of Neuropsychology Univ. of Texas Southwestern Medical Center Dallas, TX  75390-9044 MedicalResearch.com Interview with:
C. Munro Cullum, PhD, ABPP
Professor of Psychiatry and Neurology & Neurotherapeutics
Pamela Blumenthal Distinguished Professor of Clinical Psychology
Chief of Psychology , Director of Neuropsychology
Univ. of Texas Southwestern Medical Center Dallas, TX

Medical Research: What is the background for this study? What are the main findings?

Dr. Cullum: My colleague and principal investigator of the study, Dr. John Hart and I have been interested in the acute and longer-term effects of traumatic brain injury for years, and because of my roles in the Alzheimer’s Disease Center and the Texas Institute for Brain Injury and Repair at the University of Texas Southwestern Medical Center, it seemed like a natural to begin studying older individuals with and without cognitive disorder who have a history of traumatic brain injury.  Our main findings are two-fold:

First, we demonstrated that a history of concussion with loss of consciousness (which make up only about 10% of all concussions) was associated with smaller memory centers in the brain (the hippocampus) and lower memory results in our sample of retired professional football players. Concussions that did not result in loss of consciousness did not show that same strong association.

Second, our data suggest that patients with a clinical diagnosis of mild cognitive impairment (ie a memory disorder that does not grossly impair overall functioning but may lead to dementia) who also have a history of concussion with loss of consciousness show worse memory results and more brain atrophy than similar individuals diagnosed with mild cognitive impairment in the absence of a history of concussion.

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Statin Users Have Increased Risk Of Diabetes and Obesity

Ishak Mansi, MD Staff Internist, VA North Texas Health System.   Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TXMedicalResearch.com Interview with:
Ishak Mansi, MD
Staff Internist, VA North Texas Health System.
Professor in Department of Medicine &
Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TX

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

Dr. Mansi:  Statin use is associated with increased incidence of diabetes, and possibly increased body weight, and less exercise capacity. Data on the long-term effects of these associations in healthy adults are very limited. Additionally, the effects of these associations on diabetic complications have not been adequately studied.

Dr. Mansi at VA North Texas Health System, Dallas and Professor of Medicine and Clinical Sciences at the University of Texas Southwestern, Dallas, TX and his colleagues found that among generally healthy individuals, statin-users in comparison to non-users had a higher odds of being diagnosed with new onset diabetes, diabetes with complications, and overweight/obesity.

The researchers examined the records of tens of thousands of Tricare beneficiaries, during the period from 10/1/2003 to 3/1/2012. After excluding patients who had at baseline a preexisting cardiovascular diseases or severe chronic diseases that may be life-limiting (including diabetes mellitus), they identified a cohort of 25,970 patients as “healthy cohort”. They, further, matched 3,351 statins-users and 3,351 nonusers on several baseline characteristics to ensure comparability.

There are 3 main important findings for our study:

  1. Statin use was associated with significantly higher risk of new onset diabetes even in a very healthy population. Whereas the risk of diabetes with statins is known, it was thought that this may be due to the overall multiple risks of statin-users (that caused them to receive statins as a therapy).
  2. Statin use was associated with very high risk of diabetes complications in this healthy population: this was never shown before.
  3. Statin use is associated with higher risk of obesity: this also is widely unknown. However, few studies have noted this (one study using patient survey noted this, another study using Mendelian randomization showed it, and post-hoc analysis of a clinical trial showed that statin user gained more weight). Our study, which used a different methodology (retrospective cohort study) add another piece of evidence. Obesity is at endemic level in the US and treatment options are limited.

High-intensity statins was associated with greater risks of all outcomes.

This article is published in the Journal of General Internal Medicine (JGIM). JGIM is the official journal of the Society of General Internal Medicine.

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Novel Strategy May Lead To Elimination Of AML Stem Cells

Dr. Alec (Chengcheng) Zhang Michael L. Rosenberg Scholar in Medical Research Associate Professor of Physiology and Developmental Biology Member of the Harold C. Simmons Comprehensive Cancer Center UT Southwestern Medical CenterMedicalResearch.com Interview with:
Dr. Alec (Chengcheng) Zhang
Michael L. Rosenberg Scholar in Medical Research
Associate Professor of Physiology and Developmental Biology, Member of the Harold C. Simmons Comprehensive Cancer Center
UT Southwestern Medical Center

Medical Research: What is the background for this study? What are the main findings?

Response: Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. Treatments for AML yield poor outcomes, especially for the typical senior patients. The medical need for new therapies for AML is underscored by the fact that no new therapies for AML have been approved in over 30 years. There are over 50 experimental agents in clinical trials for the treatment of AML today, although only a few agents have promising data to date. New molecular targets and therapeutic strategies are needed for AML treatment.

In 2012, we published a paper showing that we cloned the human leukocyte immunoglobulin-like receptor B2 (LILRB2) as a receptor for several angiopoietin-like proteins (Angptls) (Zheng et al 2012 Nature 485:656-660). The LILRB family receptors contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and are classified as inhibitory receptors because ITIM motifs can recruit phosphatases SHP-1, SHP-2, or SHIP to negatively regulate immune cell activation. Surprisingly, in that work, we showed that PirB, the mouse ortholog of LILRB2, is expressed by AML stem cells (AML-SCs) and supports AML development. Although counterintuitive, this result is consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system.

In the current paper, we continued the research and report that a number of receptors containing the ITIMs are crucial for the development of AML. We mainly focus on studying the function and downstream signaling of LAIR1 as a representative ITIM-containing receptor. We found that the deletion of LAIR1 does not affect normal hematopoiesis but abolishes leukemia development in several different mouse leukemia models. We also identified a mechanism by which LAIR1 supports AML development, showing that the LAIR1/SHP-1/CAMK1/CREB pathway sustains the survival and self-renewal of AML cells. Importantly, our findings are well supported by bioinformatics analysis of AML patient databases and experimental results of human leukemia cells. Since certain ITIM-containing receptors are essential for AML cells but not critical for normal hematopoiesis, and blocking their signaling can boost immunity, these ITIM-containing receptors including LAIR1 represent ideal targets for treating AML.

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Genetic Diversity of Pancreatic Cancer May Lead To Therapeutic Targets

Dr. Agnieszka Witkiewicz MD Associate Professor of Pathology Harold C. Simmons Comprehensive Cancer Center UT SouthwesternMedicalResearch.com Interview with:
Dr. Agnieszka Witkiewicz MD
Associate Professor of Pathology
Harold C. Simmons Comprehensive Cancer Center
UT Southwestern

MedicalResearch: What is the background for this study?

Dr. Witkiewicz: Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis, with a five year survival rate of approximately 6%. This poor outcome is related to multiple factors, including the relatively late stage of diagnosis, many patients presenting with unresectable disease, and therapy recalcitrance resulting in disease recurrence in spite of operable disease and systemic therapy. Thus far, insights into how to target the treatment of Pancreatic ductal adenocarcinoma have remained unclear in spite of prior sequencing efforts.

MedicalResearch: What are the main findings?

Dr. Witkiewicz: The underlying critical finding of the study was that Pancreatic ductal adenocarcinoma is genetically diverse and that, in principle, this diversity could be exploited for the treatment of disease.   Specifically, many cases harbored deregulation in pathways that are the target for drug development.   For example, we identified cases that were driven by BRAF V600E and that were sensitive to the FDA approved drug Vemurafenib.   Similarly, multiple cases harbored defects in DNA repair processes that impart sensitivity to select chemotherapeutic agents and PARP inhibitors.  Common pathway deregulation was observed in reference to beta-catenin, notch, hedgehog, chromatin remodeling, and cell cycle regulatory pathways that are all targets for therapeutic intervention.

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Nuts May Lower Odds Of Metabolic Syndrome In Adolescents

Dr. Roy Kim, MD Depts. Endocrinology and Pediatrics UT Southwestern Medical CenterMedicalResearch.com Interview with:
Dr. Roy Kim, MD
Depts. Endocrinology and Pediatrics
UT Southwestern Medical Center

Medical Research: What was the problem you were focused on?

Dr. Kim: We were focused on the problem of adolescent metabolic syndrome, a major public health problem. Our objective was to determine whether nut intake is linked with any difference in odds for metabolic syndrome in US adolescents.

Medical Research: How is metabolic syndrome defined?

Dr. Kim: In general it is diagnosed when there are 3 or more of the following things: increased belly fat, high blood pressure, high fasting glucose, elevated triglycerides, and low HDL cholesterol.

Medical Research: How did you do your study?

Dr. Kim: We used data from the National Health and Nutrition Examination Survey (NHANES), years 2003-2010, to examine health status and the diet history for 2,322 US adolescents age 12 to 19 years.

Dr. Kim: Our first major finding was that adolescents who ate at least 12.9 grams of nuts per day – this is the equivalent of about 1 ounce of nuts 3 times per week – had a dramatically lower odds for metabolic syndrome compared to adolescents who ate less than that amount. The odds for nut-consumers was only about 43% of the odds for non-consumers. This remained true after controlling for age, gender, race, income, and dietary factors including sugar, fruit, and vegetable intake.

Our second major finding was that average nut intake is very low among US adolescents – only about 5 grams per day – and more than 75% of US adolescents eat no nuts at all on a typical day.

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Non-Small Cell Lung Cancer: Stereotactic Radiation Plus Chemo Improved Survival

Dr. Puneeth Iyengar (left) and Dr. Robert Timmerman

Dr. Puneeth Iyengar (left) and Dr. Robert Timmerman

MedicalResearch.com Interview with:
Dr. Puneeth Iyengar, MD, PhD
.
Assistant Professor Director of Clinical Research
Dept of Radiation Oncology Co-leader, Thoracic Disease Oriented Team Harold Simmons Cancer Center
UT Southwestern Medical Center  Dallas, TX

Medical Research: What is the background for this study? What are the main findings?

Response: Stage IV Non-small cell lung cancer (NSCLC) remains a disease of limited survival, in the range of one year for a majority of patients who historically have gone on to receive systemic therapy only. Disease in this patient population most often recurs in the sites of original gross disease. With greater understanding of the biology and patterns of failure that occur in stage IV NSCLC, it is becomingly increasingly obvious that there are subsets of patients, those with limited sites of metastatic disease, who may benefit with more aggressive local therapy in addition to systemic agents to effectuate longer progression free survival (PFS) and potentially overall survival (OS). Since failures of treatment occur most commonly in original gross deposits, local non-invasive therapy in the form of stereotactic body radiation therapy (SBRT) may offer a means to curtail the recurrences, perhaps as a way to shift the time to and patterns of failure.

To address these concepts, a multi institutional single arm phase II study was conducted at UT Southwestern Medical Center in Dallas and University of Colorado Medical Center. Twenty-four patients with limited metastatic NSCLC (fewer than or equal to six sites of disease including the primary) who had progressed through at least one systemic therapy regimen were treated with SBRT to all sites of gross disease and the EGFR inhibitor erlotinib with progression free survival the primary end point. The results of the study were very significant, with a PFS in this study cohort of 14.7 months, compared to historical ranges of 2-4 months, and an OS of 20.4 months, compared to historical ranges of 6-9 months for this same patient population. The SBRT treatments were found to be very safe and efficacious – only 3 out of 47 measurable lesions irradiated recurred with a concomitant shift in failure patterns from local to distant sites. As importantly, EGFR status was evaluated in 13 patient tumors, with none harboring the most common mutations. One could, therefore, predict that with a mutation enriched population, the combination of EGFR inhibitor and SBRT may have offered even greater PFS and OS benefits. Our observations also suggest that the SBRT treatments probably contributed the most to the dramatic PFS and OS outcomes.

These findings were published in the Journal of Clinical Oncology in the December 1, 2014 print issue with an accompanying editorial.

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Polysomnography Remains Standard For Pediatric Obstructive Sleep Apnea Diagnosis

Ron B. Mitchell, MD Professor of Otolaryngology and Pediatrics William Beckner Distinguished Chair in Otolaryngology Chief of Pediatric Otolaryngology UT Southwestern and Children's Medical Center Dallas ENT Clinic Dallas, TX 75207MedicalResearch.com Interview with:
Ron B. Mitchell, MD

Professor of Otolaryngology and Pediatrics
William Beckner Distinguished Chair in Otolaryngology
Chief of Pediatric Otolaryngology
UT Southwestern and Children’s Medical Center Dallas
ENT Clinic Dallas, TX 75207

Medical Research: What is the background for this study? What are the main findings?

Dr. Mitchell: The “gold standard” for the diagnosis of and quantification of obstructive sleep apnea (OSA) is polysomnography (PSG or a ‘sleep study’). However, the majorities of T&A procedures are done without PSG and are based on a clinical diagnosis. This is because PSG is expensive, requires overnight observation and is often unavailable. It is important to diagnose and quantify OSA as it allows for surgical planning and predicts the need and type of treatment after surgery.

We used data from the Childhood Adenotonsillectomy (CHAT) study; a large multicenter
trial (RCT), to look at the ability of clinical parameters to predict the severity of obstructive sleep apnea in children scheduled for a T&A.

The main findings of the study are that certain clinical parameters such as obesity and African American race as well as high scores on certain validated questionnaires (such as the pediatric sleep questionnaire- PSQ) are associated, but cannot predict OSA severity. PSG remains the only way to measure objectively the severity of OSA.

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Prior Cancer Excludes Many Patients From Lung Cancer Trials

Dr. David Gerber MD Associate Professor of Internal Medicine Division of Hematology and Oncology Harold C. Simmons Cancer Center at UT Southwestern Medical CenterMedicalResearch.com Interview with:
Dr. David Gerber MD
Associate Professor of Internal Medicine
Division of Hematology and Oncology
Harold C. Simmons Cancer Center at UT Southwestern Medical Center

Medical Research: What are the main findings of the study?

Dr. Gerber: Fewer than 3% of adult cancer patients in the United States are enrolled in clinical trials.  Increasingly numerous and stringent eligibility criteria are a major factor limiting participation in clinical trials.  We examined the longstanding and widespread practice of excluding patients with prior cancer from oncology clinical trials.  This policy presumably reflects concerns that a prior cancer would interfere with the conduct, outcomes, or interpretation of a clinical trial, although there is no clear evidence supporting that assumption.

We examined more than 50 National Cancer Institute (NCI)-sponsored lung cancer clinical trials.  We found that 80% excluded patients with prior cancers.  This exclusion criterion was applied broadly, including to more than two-thirds of trials with non-survival endpoints.  We then examined national Surveillance Epidemiology and End Results (SEER)-Medicare linked data to estimate the proportion of patients who would be excluded from these trials due to prior cancer.  We found that up to 18% of potential patients are excluded for this reason alone.  In large phase 3 clinical trials, that corresponds to more than 200 patients.

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After Heart Attack: High Dose Aspirin Still Commonly Prescribed

MedicalResearch.com Interview with:
Hurst M. Hall, MD and Sandeep Das, MD, MPH
Division of Cardiology
University of Texas Southwestern Medical Center
Dallas, TX

Medical Research: What are the main findings of the study?

Answer: Most patients treated for a heart attack in the United States during this study period were discharged home on 325 mg of aspirin a day.  This was true even among subgroups expected to be at high bleeding risk. In addition, there was tremendous variability in the proportional use of this higher dose aspirin across hospitals, suggesting a prominent local influence on prescribing patterns.
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Hospitalized Pneumonia Patients May Benefit from Azithromycin

Dr. Eric M. Mortensen, M.D., M.Sc. VA North Texas Health Care System and University of Texas Southwestern Medical Center, DallasMedicalResearch.com Interview with:
Dr. Eric M. Mortensen, M.D., M.Sc.
VA North Texas Health Care System and
University of Texas Southwestern Medical Center, Dallas

 

MedicalResearch: What are the main findings of the study?

Dr. Mortensen: The main findings of our study was that for older patients hospitalized with pneumonia that with the use of azithromycin although there is a small increase in the number of non-fatal heart attacks there was a much lower decrease in mortality.   In addition there were no other significant increases in cardiac events.  So the overall risk:benefit ratio was that for each non-fatal heart attack there were 7 deaths that were prevented.
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Cirrhosis: Data Supports Surveillance for Liver Cancer Screening

Amit Singal MD MS Assistant Professor of Medicine Medical Director, Liver Tumor Program Dedman Scholar of Clinical Care Division of Digestive and Liver Diseases University of Texas Southwestern Dallas TX 75201 - 8887MedicalResearch.com Interview with:
Amit Singal MD MS
Assistant Professor of Medicine
Medical Director, Liver Tumor Program
Dedman Scholar of Clinical Care
Division of Digestive and Liver Diseases
University of Texas Southwestern
Dallas TX 75201 – 8887

MedicalResearch: What are the main findings of the study?

Dr. Singal: We conducted a meta-analysis of current studies to characterize the association between hepatocellular carcinoma surveillance and early detection, curative treatment rates, and overall survival in patients with cirrhosis.  We identified 47 studies with 15,158 patients, of whom 6,284 (41.4%) had hepatocellular carcinoma  detected by surveillance. Hepatocellular carcinoma  surveillance was associated with improved early stage detection (OR 2.08, 95% CI 1.80–2.37) and curative treatment rates (OR 2.24, 95% CI 1.99–2.52). These associations were robust to several sensitivity analyses, including study design, study location, and study period. Hepatocellular carcinoma  surveillance was associated with significantly prolonged survival (OR 1.90, 95% CI 1.67–2.17), which remained significant in the subset of studies adjusting for lead-time bias. Three-year survival rates were 50.8% among patients who underwent surveillance, compared to only 28.2% among hepatocellular carcinoma  patients with tumors detected outside of a surveillance program.

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Lung Cancer: Germline Mutation Predisposes Women Who Never Smoked

Dr. Azi  Gazdar, MD UT Southwestern Medical Center W. Ray Wallace Distinguished Chair in Molecular Oncology Research Hamon Center for Therapeutic Oncology, PathologyMedicalResearch.com Interview with:
Dr. Azi  Gazdar, MD
UT Southwestern Medical Center
W. Ray Wallace Distinguished Chair in Molecular Oncology Research
Hamon Center for Therapeutic Oncology, Pathology


MedicalResearch.com: What are the main findings of the study?

Dr. Gazdar: We describe the characteristics of lung cancers arising in subjects who inherited a germline mutation that predisposes to lung cancer.  The mutation is rare in the general populations, and is inherited equally by both sexes.  However it is a potent predisposing gene, and one third of the never smoking carriers will develop lung cancer.  Thus, about 1% of patients who develop lung cancer carry the germline mutation.  This figure may rise as awareness of the condition and its link to lung cancer is raised among doctors diagnosing lung cancer. However, lung cancers mainly develop in women who are lifetime never smokers.  Lung cancer development is much less common among smokers and men, although accurate figures are not yet available. So the risk among carriers is somewhat similar to the BRCA genes predisposing to breast cancer, where a female carrier has about a 50% lifetime chance of developing breast cancer.

The specific germline mutation (known as T790M) occurs in a gene known as epidermal growth factor receptor (EGFR) gene.  Sporadic mutations in this gene usually predict for effective responses to a class of drugs known as tyrosine kinase inhibitors (TKIs), which are widely used in the treatment of lung cancer.  However, the T790M mutation, when it occurs in sporadic tumors not associated with germline inheritance are resistant to TKI therapy.  Thus the prediction is that lung cancers arising in carriers with the germline mutation would also be resistant to TKI therapy.
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Improving Suceess of Corneal Transplantation

Dr. Jerry Y. Niederkorn, Ph.D. George A. and Nancy P. Shutt Professorship in Medical Sciences Royal C. Miller Chair in Age-Related Macular Degeneration Research Professor of Ophthalmology and Microbiology Vice Chair, Research (Department of Ophthalmology) Department of Ophthalmology, University of Texas Southwestern Medical Center Dallas, TXMedicalResearch.com Interview with:
Dr. Jerry Y. Niederkorn, Ph.D.
George A. and Nancy P. Shutt
Professorship in Medical Sciences
Royal C. Miller Chair in Age-Related Macular Degeneration Research Professor of Ophthalmology and Microbiology
Vice Chair, Research (Department of Ophthalmology)
Department of Ophthalmology, University of Texas Southwestern Medical Center
Dallas, TX

FN-γ Blocks CD4+CD25+ Tregs and Abolishes Immune Privilege of Minor Histocompatibility Mismatched Corneal Allografts

MedicalResearch.com: What are the main findings of the study?

Dr. Niederkorn: These findings indicate that a combination of two simple maneuvers increases the acceptance of corneal transplants. In the past, there was no clear benefit in performing tissue matching of the cornea donor’s major histocompatibility complex (MHC) with the recipient of the corneal transplant. However, our study in experimental animals revealed that blocking a single immune system molecule called interferon-gamma (IFN-γ) combined with matching the corneal transplant donor with the transplant recipient’s MHC gene complex reduced the risk of rejection to less than 10% in the total absence of anti-rejection drugs. This study revealed that blocking this single immune system molecule promoted the development of immune system cells called T regulatory cells (Tregs) that suppressed the lymphocytes that are responsible for attacking organ transplants.
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Resistant Hypertension: Better Control With Therapeutic Drug Monitoring

Dr. Wanpen Vongpatanasin, MD Professor of Medicine Director, Hypertension Section Cardiology Division UT Southwestern Medical CenteMedicalResearch.com Interview with;
Dr. Wanpen Vongpatanasin, MD
Professor of Medicine
Director, Hypertension Section, Cardiology Division
UT Southwestern Medical Center


MedicalResearch.com: What are the main findings of the study?

Dr. Vongpatanasin: We found that more than 50% of patients with resistant hypertension were non-adherent to at least one drug prescribed by their primary care physicians for blood pressure control.

When we provided this information back to the patients, as part of care in our hypertension specialty clinic, we found that many patients report difficulty taking prescribed medications due to either associated side effects or cost of the medication. When we adjusted patient’s medications to fit their needs, BP levels were substantially improved during subsequent visits without increasing the number of medications.
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Breast Cancer: Axillary Node Interventions

Roshni Rao, MD Division of Surgical Oncology, Department of Surgery University of Texas Southwestern Medical Center, DallasMedicalResearch.com Interview with:
Roshni Rao, MD

Division of Surgical Oncology, Department of Surgery
University of Texas Southwestern Medical Center, Dallas

MedicalResearch.com: What are the main findings of the study? 

Dr. Rao: That in most women with small breast cancer (<3.0cm in size), it is not necessary to removal all the lymph nodes underneath the arm, even if those nodes do have cancer. Radiation therapy, which is required after a partial mastectomy for breast cancer, can prevent these nodes from growing or becoming clinically significant.

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Emergence of New Fat Cells and Response to Diet and Cold

Philipp E. Scherer, PhD Professor, Department of Internal Medicine Gifford O. Touchstone Jr. and Randolph G. Touchstone Distinguished Chair in Diabetes Research Director, Touchstone Diabetes Center The University of Texas Southwestern Medical Center 5323 Harry Hines Blvd. Dallas, TX 75390-8549MedicalResearch.com Interview with:
Philipp E. Scherer, PhD
Professor, Department of Internal Medicine
Director, Touchstone Diabetes Center
The University of Texas Southwestern Medical Center
Dallas, TX 75390-8549

MedicalResearch.com: What are the main findings of the study?

Dr. Scherer: This is the first study that tracks the emergence of new fat cells in response to various physiological stimuli, such as high fat diet and cold exposure.  Continue reading

Myocardial Fat Content : Effects of Age and Aerobic Fitness

Dr. Satyam Sarma MD Assistant Instructor, Cardiology University of Texas, Southwestern Medical Center Inst. for Exercise and Environmental Medicine 7232 Greenville Ave. Dallas TX 75231MedicalResearch.com Interview with:
Dr. Satyam Sarma MD
Assistant Instructor, Cardiology
University of Texas, Southwestern Medical Center
Inst. for Exercise and Environmental Medicine
7232 Greenville Ave. Dallas TX 75231


MedicalResearch.com: What are the main findings of the study?

Dr. Sarma: The main findings of our study were that as we age or live a sedentary lifestyle, fat tends to accumulate in the muscle of the heart. The accumulation of myocardial lipids were linked to abnormalities in diastolic function. With increasing levels of fat, the left ventricle became less distensible and had impaired tissue relaxation.
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Community Disasters: Mental Health Response

Carol S. North, MD, MPE  The Nancy and Ray L. Hunt Chair in Crisis Psychiatry Director, Program in Trauma and Disaster, VA North Texas Health Care System 4500 S. Lancaster Rd., Dallas, TX 75216 Professor of Psychiatry and Surgery/Division of Emergency Medicine UT Southwestern Medical Center 6363 Forest Park Rd. Dallas, TX 75390-8828MedicalResearch.com Interview with:
Carol S. North, MD, MPE

The Nancy and Ray L. Hunt Chair in Crisis Psychiatry
Director, Program in Trauma and Disaster,
VA North Texas Health Care System
4500 S. Lancaster Rd., Dallas, TX 75216
Professor of Psychiatry and Surgery/Division of Emergency Medicine
UT Southwestern Medical Center
6363 Forest Park Rd. Dallas, TX 75390-8828

MedicalResearch.com: What are the main findings of the study?

Answer: In post-disaster settings, a systematic framework of case identification, triage, and mental health interventions can guide overall mental health response and should be integrated into emergency medicine and trauma care responses.
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Transthoracic Echocardiograms: Most Lead to No Appreciable Change in Patient Care

Susan Matulevicius, MD, MSCS  Department of Medicine, The University of Texas Southwestern Medical Center, DallasMedicalResearch.com Interview with:
Susan Matulevicius, MD, MSCS

Department of Medicine, The University of Texas Southwestern Medical Center, Dallas

MedicalResearch.com: What are the main findings of the study?

Dr. Matulevicius: In our cohort of 535 transthoracic echocardiograms performed at a single academic medical center, we found that the majority (92%) of echocardiograms were appropriate by the 2011 Appropriate Use Criteria; however, only 1 in 3 echocardiograms lead to an active change in patient care while 1 in 5 resulted in no appreciable change in patient care.
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Depressive symptoms and white matter dysfunction in retired NFL players with concussion history

MedicalResearch.com eInterview with:

John Hart, M.D. Medical Science Director at the Center for BrainHealth Jane and Bud Smith Distinguished Chair Cecil Green Distinguished Chair The University of Texas at DallasJohn Hart, M.D.
Medical Science Director at the Center for BrainHealth
Jane and Bud Smith Distinguished Chair
Cecil Green Distinguished Chair
The University of Texas at Dallas

MedicalResearch.com: What are the main findings of the study?

Dr. Hart: Football players often sustain numerous concussive and subconcussive impacts—head impacts that do not elicit neurologic symptoms that may lead to white matter damage. We evaluated a population of retired NFL players in order to study the relationship between white matter integrity and the manifestation of depressive symptoms. We identified, for the first time, a correlation between depression and white matter abnormalities in former players with a remote history of concussion using diffusion tensor imaging (DTI).

Our data demonstrated a significant association between white matter integrity, as measured by DTI Fractional Anisotropy (FA), and the presence as well as severity of depressive symptoms in retired NFL athletes with a history of concussive or subconcussive impacts. We also found that dysfunction of the anterior aspect of the corpus callosum (forceps minor) and its projections to the frontal lobe can identify those with depression with 100% sensitivity and 95% specificity.

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Rapid Improvement of Diabetes After Gastric Bypass Surgery: Is It the Diet or Surgery?

MedicalResearch.com Author Interview: Ildiko Lingvay, MD, MPH, MSCS
Departments of Internal Medicine–Endocrinology and Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas

MedicalResearch.com: What are the main findings of the study?

Dr. Lingvay: We found that the restrictive diet imposed after a bariatric procedure like RYGB is the key element to the rapid improvement in the diabetes seen immediately after surgery.

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Novel Susceptibility Variants at 10p12.31-12.2 for Childhood Acute Lymphoblastic Leukemia in Ethnically Diverse Populations

MedicalResearch.com Author Interview: Jun J. Yang, Ph.D.

Assistant Member Dept. of Pharm. Sci.
St. Jude Children’s Research Hospital
262 Danny Thomas Pl., MS313 Memphis, TN 38105

MedicalResearch.com: What are the main findings of the study?

Dr. Yang: We performed a comprehensive survey of inherited genetic variations for their contribution to the susceptibility of acute lymphoblastic leukemia (ALL), the most common cancer in children. This is by far the largest study of its kind (in terms of the number of subjects involved), and also the first one to include multi-ethnic populations. We identified 4 genomic loci related to the predisposition to ALL, 2 of which contributed to racial differences in the incidence of ALL.  This study provided unequivocal evidence for inherited susceptibility of childhood ALL and pointed to novel biology of the pathogenesis of this disease.
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Scientists create small molecules that alter biological clock and lead to weight loss

The new molecules could lead to unique treatments for obesity, diabetes, high cholesterol, and sleep disorders

JUPITER, FL — Scientists from the Florida campus of The Scripps Research Institute have synthesized a pair of small molecules that dramatically alter the core biological clock in animal models, highlighting the compounds’ potential effectiveness in treating a remarkable range of disorders—including obesity, diabetes, high cholesterol, and serious sleep disorders.

The study was published on March 29, 2012, in an advance, online edition of the journal Nature.

The study showed that when administered in animal models the synthetic small molecules altered circadian rhythm and the pattern of core clock gene expression in the brain’s hypothalamus, the site of the master cellular clock that synchronizes daily rhythms in mammals; circadian rhythms are the physiological processes that respond to a 24-hour cycle of light and dark and are present in most living things.

When given to diet-induced obese mice, these same small molecules decreased obesity by reducing fat mass and markedly improving cholesterol levels and hyperglycemia—chronically high blood sugar levels that frequently lead to diabetes.

“The idea behind this research is that our circadian rhythms are coupled with metabolic processes and that you can modulate them pharmacologically,” said Thomas Burris, a professor at Scripps Florida who led the study. “As it turns out, the effect of that modulation is surprisingly positive—everything has been beneficial so far.”

Burris stressed that these compounds were first generation—the first to hit their targets in vivo with room for improvement as potential treatments. “In terms of therapeutics, this is really the first step,” he said.

In the new study, the team identified and tested a pair of potent synthetic compounds that activate proteins called REV-ERBα and REV-ERBβ, which play an integral role in regulating the expression of core clock proteins that drive biological rhythms in activity and metabolism.

In the study, the scientists observed clear metabolic effects when the synthetic compounds were administered twice a day for 12 days. Animals displayed weight loss due to decreased fat mass with no changes in the amount of food they ate. The animals followed the human model of obesity closely, eating a standard Western diet of high fat, high sugar foods, yet still lost weight when given the compounds.

In one of the study’s more striking findings, both synthetic compounds were shown to reduce cholesterol production. Cholesterol in the blood of treated animal models decreased 47 percent; triglycerides in the blood decreased 12 percent.

The circadian pattern of expression of a number of metabolic genes in the liver, skeletal muscle, and in fat tissue was also altered, resulting in increased energy expenditure, something of a surprise. In the study, the scientists observed a five percent increase in oxygen consumption, suggesting increased energy expenditure during the day and at night. However, these increases were not due to increased activity—the animals displayed an overall 15 percent decrease in movement during those same time periods.

In addition to its impact on metabolism, the two compounds also affected the animals’ activity during periods of light and darkness, suggesting that this class of compound may be useful for the treatment of sleep disorders, including the common problem of jet lag.

The first authors of the study, “Regulation of Circadian Behavior and Metabolism by Synthetic REV‐ERB Agonists,” are Laura A. Solt and Yongjun Wang of Scripps Research. Other authors include Subhashis Banerjee, Travis Hughes, Douglas J. Kojetin, Thomas Lundasen, Youseung Shin, Jin Liu, Michael D. Cameron, Romain Noel, Andrew A. Butler, and Theodore M. Kamenecka of Scripps Research; and Seung Hee Yoo and Joseph S. Takahashi of the Howard Hughes Medical Institute and University of Texas Southwestern Medical Center.