Schizophrenia: SynCav1 As Potential Target To Restore Neuron Function

MedicalResearch.com Interview with:

Brian P. Head, MS, PhD Associate Professor, UCSD Research Scientist, VASDHS Department of Anesthesiology VA San Diego Healthcare System San Diego, CA 92161-9125

Dr. Brian Head

Brian P. Head, MS, PhD
Associate Professor, UCSD
Research Scientist, VASDHS
Department of Anesthesiology
VA San Diego Healthcare System
San Diego, CA 92161-9125

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

Response: DISC1 is a schizophrenia associated gene originally identified in a Scottish family. DISC1 protein is highly expressed in the developing brain and in the dentate gyrus of the adult hippocampus, and is involved in neuritogenesis and neuronal signaling. DISC1 is located in multiple intracellular locations including axons and synapses, and loss of DISC1 function causes deficits in neural development, neuronal proliferation, axonal growth, and cytoskeleton modulation, which are consistent with abnormal neural development in schizophrenia.

SynCav1 means synapsin-driven caveolin construct. Synapsin promoter is neuronal specific which allows us to increase caveolin expression-specifically in neurons. We have previously shown that SynCav1 increases neuronal signaling and dendritic growth and arborization in vitro (Head BP JBC 2011), and when delivered in vivo augments functional neuroplasticity and improves learning and memory in adult and aged mice (Mandyam CD Biol Psych 2015).

Since loss of DISC1 function equates to schizophrenic-like symptoms, then decreased DISC1 expression in Cav-1 KO mice agrees with this premise. Thus, loss of Cav-1 increases their likelihood of developing schizophrenia-like symptoms. Because re-espression of Cav-1 restored DISC1 expression as well as expression of key synaptic proteins, this proof-of-concept findings not only builds upon our previously results demonstrating that Cav-1 is critical for neuronal signaling and functional synaptic plasticity but also strongly links Cav-1 with maintaining normal DISC1 expression levels and potentially attenuating schizophrenia-like symptoms.

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Many Atrial Fibrillation Patients At Risk of Stroke Receive Aspirin Instead of Appropriate Anticoagulation

MedicalResearch.com Interview with:

Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS Assistant Professor Cardiac Electrophysiology, Division of Cardiology University of California, San Diego (UCSD)

Dr. Jonathan Hsu

Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS
Assistant Professor
Cardiac Electrophysiology, Division of Cardiology
University of California, San Diego (UCSD)

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

Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and imparts significant stroke risk. In patients with AF determined to be at intermediate to high risk for thromboembolism, anticoagulation with warfarin (a vitamin K antagonist) or the newer non-vitamin K antagonist oral anticoagulants clearly reduces morbidity and mortality compared to aspirin. We sought to evaluate practice patterns of cardiovascular specialists in the United states to determine how often AF patients at risk for stroke are prescribed aspirin over oral anticoagulation, and predictors of this practice.

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JAMA Study Looks At Comparable Effectiveness of Four Weight Loss Medications

MedicalResearch.com Interview with:

Siddharth Singh, MD, MS Postdoctoral Fellow, NLM/NIH Clinical Informatics Fellowship Division of Biomedical Informatics Clinical Assistant Professor of Medicine, Division of Gastroenterology, Department of Internal Medicine, University of California San Diego, La Jolla

Dr Siddharth Singh

Siddharth Singh, MD, MS
Postdoctoral Fellow, NLM/NIH Clinical Informatics Fellowship
Division of Biomedical Informatics
Clinical Assistant Professor of Medicine, Division of Gastroenterology, Department of Internal Medicine,
University of California
San Diego, La Jolla

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

Dr. Singh: Over the last 4 years, four new medications have been approved for long-term use for weight loss by the FDA. We sought to evaluate the comparative effectiveness and tolerability of these medications through a systematic review and network meta-analysis. Based on 28 trials in over 29,000 overweight or obese patients, we observed that magnitude of weight loss achieved with these agents is variable, ranging from 2.6kg with orlistat to 8.8kg with phentermine-topiramate. Over 44-75% of patients are estimated to lose at least 5% body weight, and 20-54% may lose more than 10% of body weight; phentermine-topiramate was the most efficacious, whereas lorcaserin was the best tolerated.

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Biomarker Based Chemotherapy Approach Improved Outcomes

MedicalResearch.com Interview with:

Maria Schwaederle PharmD Clinical Research Scientist Center for Personalized Cancer Therapy UCSD Moores Cancer Center La Jolla, CA 92093

Dr. Maria Schwaederle

Maria Schwaederle PharmD
Clinical Research Scientist
Center for Personalized Cancer Therapy
UCSD Moores Cancer Center
La Jolla, CA 92093

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

Dr. Schwaederle: We performed this analysis with experts in the field, including but not limited to Drs Schilsky, Lee, Mendelsohn and Kurzrock, all known for their experience in the area of precision/personalized medicine.
Historically, phase I trials (which are often first in human or highly experimental in other ways) were believed to be examining only toxicity. Our meta-analysis of 13,203 patients shows that in the era of precision medicine, this historical belief needs to be discarded. Second, it is the use of precision medicine that makes this belief outdated.
Indeed, Phase I trials that utilized a biomarker-driven approach that is the essence of precision medicine had a median response rate of about 31%, which is higher than many FDA approved drugs, and this is in spite of the fact that phase I patients are a highly refractory group having failed multiple lines of conventional therapy.

Importantly, however, it was not the use of targeted agents alone that was important. It was the biomarker-based approach where patients are matched to drugs. Without matching, response rates were dismal—about 5%.

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No Apparent Increase in Neuropsychiatric Side Effects From Smoking Cessation Mediations

MedicalResearch.com Interview with:

Robert M. Anthenelli, M.D. Professor and Executive Vice Chair Director, Pacific Treatment and Research Center Department of Psychiatry University of California, San Diego, Health Sciences

Dr. Robert Anthenelli

Robert M. Anthenelli, M.D.
Professor and Executive Vice Chair
Director, Pacific Treatment and Research Center
Department of Psychiatry
University of California, San Diego, Health Sciences 

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

Dr. Anthenelli: Despite growing evidence to the contrary, significant concerns have been raised about the neuropsychiatric safety risk of the smoking cessation medications, varenicline and bupropion. What has been lacking until now among individuals with and without psychiatric disorders is a large, randomized controlled trial that directly compares these medications with placebo and an active comparator (nicotine patch) and that systematically probes for neuropsychiatric adverse events while smokers are trying to quit.

MedicalResearch.com: What are the main findings?

Dr. Anthenelli:

1) Neither varenicline nor bupropion significantly increased incidence of moderate-to-severe neuropsychiatric adverse events relative to placebo or nicotine patch in smokers without or with stable psychiatric disorders.

2) Regardless of treatment condition, smokers with a history of or a current stable psychiatric disorder reported more neuropsychiatric adverse events than their counterparts without such conditions.

3) Varenicline was more effective than placebo, nicotine patch, and bupropion in helping smokers achieve abstinence; bupropion and nicotine patch were more effective than placebo.

4) While quit rates overall were slightly lower in smokers with psychiatric disorders compared with cessation rates in individuals without these conditions, all three medications were more effective than placebo, and their relative efficacy (varenicline > bupropion = nicotine patch > placebo) was the same in this special population of smokers as it was for smokers without mental health disorders.

EAGLES is the first trial to have compared the smoking cessation efficacy of the three, first-line smoking cessation medications in smokers with current or past psychiatric disorders. These results are important because individuals with mental health conditions are disproportionately affected by smoking-related diseases and death.

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Anthenelli:

1) In the context of a growing body of studies finding no evidence of a greater incidence of serious neuropsychiatric adverse events in users of varenicline and bupropion compared with nicotine replacement therapy or placebo, it appears these non-nicotine medications can be used safely by psychiatrically stable smokers.

2) Smokers with a history of or current stable psychiatric disorder are more prone to exhibit such events regardless of the medication used and should be monitored during a quit attempt.

3) Varenicline demonstrates superior efficacy to bupropion and nicotine patch, but all three medications are more effective than placebo in smokers with and without stable psychiatric disorders.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Anthenelli: We are looking forward to conducting secondary analyses of the large EAGLES dataset to examine, in finer detail, the safety and efficacy of the three first-line medications in sub-cohorts (e.g., smokers with major depressive disorder, bipolar disorder, and schizophrenia) of the psychiatric cohort. We will also be examining predictors of treatment response to determine whether these vary as a function of a smoker’s psychiatric history.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial

Anthenelli, Robert M et al.

The Lancet , Volume 0 , Issue 0 , Published Online: 22 April 2016

DOI: http://dx.doi.org/10.1016/S0140-6736(16)30272-0

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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More Muscle in Lean Women Linked To Lower Diabetes Risk

MedicalResearch.com Interview with:

Britta Larsen, Ph.D. Assistant Professor Family Medicine & Public Health University of California, San Diego Medical Teaching Facility La Jolla, CA 92093-0628

Dr. Britta Larsen

Britta Larsen, Ph.D.
Assistant Professor
Family Medicine & Public Health
University of California, San Diego
Medical Teaching Facility
La Jolla, CA 92093-0628 

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

Dr. Larsen: We know that muscle is important for metabolic processes, but there has been very little research on the role muscle may play in the development of metabolic diseases like type 2 diabetes. While excess fat can increase the risk of metabolic disease, there are people who are normal weight who still develop diabetes, and it’s possible that this could be due to low muscle mass. Our main findings were that, in normal weight women, women with more abdominal, thigh, and overall muscle were less likely to develop diabetes over a 13-year period. 
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Shorter Overnight Fast May Increase Risk of Breast Cancer Recurrence

MedicalResearch.com Interview with:

Ruth E. Patterson, PhD Professor, Department of Family Medicine and Public Health Associate Director, Population Sciences Program Leader, Cancer Prevention Moores Cancer Center UC San Diego La Jolla, CA

Dr. Ruth Patterson

Ruth E. Patterson, PhD
Professor, Department of Family Medicine and Public Health
Associate Director, Population Sciences
Program Leader, Cancer Prevention
Moores Cancer Center
UC San Diego
La Jolla, CA

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

Dr. Patterson: Our research team was intrigued with studies in mice showing that even when eating a high-fat diet, mice who were subjected to a 16-hour fasting regimen during the sleep phase were protected against abnormal glucose metabolism, inflammation and weight gain; all of which are associated with poor cancer outcomes.

We had access to a study conducted in breast cancer survivors called the Women’s Healthy Eating and Living Study (WHEL).  Participants in this study completed food records, which give the time of eating meals and snacks.  We used the food records to estimate the average nightly fasting interval in 2413 breast cancer survivors.  Overall, we found that women who had a nightly fasting interval of less than 13 hours had a 36% increased risk of breast cancer recurrence and a nonsignificant increase in mortality.  We also found that women with a short nightly fast had poorer glucoregulation and worse sleep, both of which might explain the link to breast cancer.

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Intracoronary Gene Transfer Improved Ejection Fraction in Heart Failure

MedicalResearch.com Interview with:

H Kirk Hammond, MD Professor of Medicine (Cardiology) University of California San Diego Veterans Affairs San Diego Healthcare System San Diego, CA 92161

Dr. H. Kirk Hammond

H Kirk Hammond, MD
Professor of Medicine (Cardiology)
University of California San Diego
Veterans Affairs San Diego Healthcare System
San Diego, CA 92161 

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

Dr. Hammond: Heart failure affects >28 million patients worldwide and is the only cardiovascular disease that is increasing in prevalence. Despite steady improvement in drug therapy for heart failure, recent hospitalization rates and mortality have changed little. New therapies are needed. Adenylyl cyclase type 6 (AC6), is a protein that catalyzes the conversion of ATP to cAMP and is an important determinant of heart function. The amount and function of AC6 are reduced in failing hearts, and preclinical studies have shown benefits of increased cardiac AC6 content on the heart. The aim of the trial was to determine safety and heart function gene transfer of AC6, achieved by intracoronary delivery of an inactivated virus carrying the gene for AC6 (Ad5hAC6) in patients with symptomatic heart failure and reduced ejection fraction. Our hypothesis was that AC6 gene transfer would safely increase function of the failing hearts of patients with heart failure.

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Dual and Concordant Vaginal and Oral HPV Infections in Women

MedicalResearch.com Interview with:

Ryan K. Orosco, MD Division of Head and Neck Surgery Department of Surgery University of California, San Diego

Dr. Ryan Orosco

Ryan K. Orosco, MD
Division of Head and Neck Surgery
Department of Surgery
University of California, San Diego

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

Dr. Orosco: Our group at UC San Diego is interested in HPV as it relates to diseases of the head and neck.  HPV is a well-publicized cause of cervical cancer, and awareness about its link to throat (oropharynx) cancer is rapidly increasing.

Less well-known, is the relationship between HPV and benign (non-cancerous) diseases such as genital warts and papilloma of the throat.  As we strive to understand how to best care for patients with HPV-related disorders, it is important to understand the entire process of disease progression, which begins with HPV infection. Our group wanted to explore the relationship between HPV infection in the two most commonly infected body sites: oral and vaginal.

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Children Can Maintain Healthy Weight By Eating Slowly

Geert W. Schmid-Schonbein, Ph.D. Distinguished Professor and Chairman Department of Bioengineering Adjunct Professor in Medicine University of California San Diego

Prof. Schmid-Schonbein

MedicalResearch.com Interview with:
Geert W. Schmid-Schonbein, Ph.D.
Distinguished Professor and Chairman
Department of Bioengineering
Adjunct Professor in Medicine
University of California San Diego

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

Dr. Schmid-Schonbein: Most approaches to control/reduce body weight focus on reducing food quantity, improving quality and promoting daily activity. These approaches, effective in the short term, only yield modest weight control. Weight management strategies recommended in the past have not significantly diminished the current trend towards childhood and adolescence obesity.

We developed and tested an alternative approach to control weight gain in healthy individuals to reduce the risk for development of obesity and diabetes complications. The essence is to:

Eat deliberately slow AND stop eating when you feel no longer hungry”.

The approach avoids any form of special diet, uses no drugs, can be adopted for a lifetime and used in any ethnic environment. Children in a Mexican School in Durango were instructed by a pediatrician to learn to eat deliberately slow and to stop eating when the satiety reflex sets in, i.e. the moment when the feeling of hunger has disappeared.

They were instructed to:

  • quench the thirst at the beginning of a meal with water,
  • use a portable 30 second hourglass sand timer,
  • take a bite only when the sand timer was turned, and
  • stop eating when they were no longer hungry (as compared to feeling of fullness), and
  • limit food consumption after the point of satiety.

Over a one-year period, children not using the hourglass excessively increased their body-mass index, while in contrast children using the hourglass grew normally their body-mass index. Body surface area and waist hip ratio followed the same trend. The study shows feasibility of regulating food intake by education that is directed at developing slow eating habits and cessation of eating at satiety. A combination of behavioral training and focused eating monitoring may constitute a weight control method that may serve a life-time and can be promoted for children and adolescents at moderate costs, on a national basis.

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Primary Care Continuity Reduced Emergency Department Use and Hospitalizations

Nadereh Pourat, PhD Professor, Department of Health Policy and Management, UCLA Fielding School of Public Health Adjunct Professor, UCLA School of Dentistry Director of Research, UCLA Center for Health Policy ResearchMedicalResearch.com Interview with:
Nadereh Pourat, PhD

Professor, Department of Health Policy and Management, UCLA Fielding School of Public Health
Adjunct Professor, UCLA School of Dentistry
Director of Research, UCLA Center for Health Policy Research

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

Dr. Pourat: We have succeeded to insure most of the uninsured population in the U.S., but now have to figure out how to reduce costs while improving health. We had the opportunity to examine the role of continuity with a primary care provider, which is one of the pathways that looked promising in improving health and reducing costs. We were evaluating a major demonstration program in California called the Health Care Coverage Initiative (HCCI) and one of the participating counties implemented a policy to increase adherence by only paying for visits if patients went to their assigned providers. We examined what happened to patients who always or sometimes adhered to their provider versus those who never adhered. We found that adherence or continuity reduced emergency department use and hospitalizations. This would lead to savings because of the high costs of these services.

Medical Research: What should clinicians and patients take away from your report?

Dr. Pourat: The study shows that both patients and clinicians would benefit from continuity with the primary care provider. Clinicians can actually make a difference in helping patients: they can teach patients about self-care and help them manage their conditions better. Patients would benefit from following through with treatment plans and experience less medical error and duplication of services which are potentially harmful. Continuity fosters rapport and trust between patients and providers and can be beneficial to both.

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Risk Score May Help Identify MSM Most In Need Of HIV Prevention Resources

MedicalResearch.com Interview with:
Dr. Martin Hoenigl
Center for AIDS Research
University of California, San Diego

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

Dr. Hoenigl: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency Virus, the risk of HIV infection within this population is not uniform. Characterizing and identifying the MSM at greatest risk for incident HIV infection might permit more focused delivery of both prevention resources and selection of appropriate interventions, such as intensive counseling, regular HIV screening with methods that detect acute infection (ie, nucleic acid amplification test), and antiretroviral preexposure prophylaxis (PrEP).

By using data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%), we were able to create the San Diego Early Test (SDET) risk score. The SDET score consist of four risk behavior variables which were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus 5 or more male partners (3 points), 10 or more male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points), all as reported for the prior 12 months. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu.

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