Prions of Creutzfeldt-Jakob Disease Detected Throughout Eye Tissues

MedicalResearch.com Interview with:
Top, retina of a control patient. Bottom, retina from a patient with CJD. Arrowheads point to abnormal prions in the outer plexiform layer (opl), and the asterisk (*) marks more diffuse prions in the inner plexiform layer (ipl).Orrù et al., mBio
Byron Caughey, Ph.D.
Senior Investigator
Chief, TSE/prion Biochemistry Section
Laboratory of Persistent Viral Diseases
NIH/NIAID Rocky Mountain Laboratories
Hamilton, MT 59840 USA 

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

Response: Corneal transplants have caused the transmission of Creutzfeldt-Jakob disease (CJD) in at least two cases, and pathological prion protein has been detected in the retinas of the eyes of sporadic CJD cases. To build on these previous indications of prions in eye tissue, we tested the distribution of prions in various components of eyes from 11 sCJD decedents.

We applied a highly sensitive surrogate test for prions (RT-QuIC) that indicated that all of the sCJD cases had prions in multiple parts of their eye, including the cornea and sclera, which is the white outer surface of the eye. Retinas were usually contained the highest levels, in some cases approaching levels in the brain. Some other parts such as the cornea, lens and vitreous had much lower, but detectable, levels. 

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Soy Formula Feeding in Infancy Linked with Menstrual Pain in Adulthood

MedicalResearch.com Interview with:

"Baby Bottle" by brokinhrt2 is licensed under CC BY 2.0Kristen Upson, PhD, MPH and
Donna D. Baird, PhD
Epidemiology Branch
National Institute of Environmental Health Sciences
Research Triangle Park, NC 27709 

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

Response: Menstrual pain is the most common menstrual complaint and can substantially affect the quality of women’s lives. A prior study in young adults who participated in feeding studies as infants reported an increased risk of greater menstrual pain severity in adulthood with soy formula feeding. Since that study, evidence from laboratory animal studies support the disruptive effects of a phytoestrogen present in soy formula, genistein, on reproductive system development, including aspects involved in menstrual pain. The laboratory animal studies also demonstrate that the developmental changes with genistein can persist into adulthood. Given these results, we were interested in further evaluating the association between infant soy formula feeding and menstrual pain in a cohort of young women.

In our study of women ages 23-35 years old, we observed that soy formula feeding during infancy was associated with several indicators of severe menstrual pain in reproductive-age women. This included a 40% increased risk of ever using hormonal contraception for menstrual pain and 50% increased risk of moderate/severe menstrual discomfort with most periods during early adulthood.  Continue reading

Probiotic May Eliminate Staph Bacteria Colonizations

MedicalResearch.com Interview with:
"staph aureus on blood agar" by Iqbal Osman is licensed under CC BY 2.0Pipat Piewngam
Postdoctorol fellow
Pathogen Molecular Genetics Section,
Laboratory of Bacteriology,
NIAID/NIH
Bethesda, MD, USA 20892 

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

Response: Our team at National Institutes of health, Mahidol University and Rajamangala University of Technology in Thailand has reported that the consumption of probiotic Bacillus bacteria comprehensively abolishes colonization with the dangerous pathogen, Staphylococcus aureus.

We hypothesized that the composition of the human gut microbiota affects intestinal colonization with S. aureus. We collected fecal samples from 200 healthy individuals from rural populations in Thailand and analyzed the composition of the gut microbiome by 16S rRNA sequencing. Surprisingly, we did not detect significant differences in the composition of the microbiome between S. aureus carriers and non-carriers. We then sampled the same 200 people for S. aureus in the gut (25 positive) and nose (26 positive). Strikingly, we found no S. aureus in any of the samples where Bacillus were present.

In mouse studies, we discovered S. aureus Agr quorum-sensing signaling system that must function for the bacteria to grow in the gut. Intriguingly, all of the more than 100 Bacillus isolates we had recovered from the human feces efficiently inhibited that system. Then, we discovered that the fengycin class of Bacillus lipopeptides achieves colonization resistance by inhibiting that system.

To further validate their findings, we colonized the gut of mice with S. aureus and fed them B. subtilis spores to mimic probiotic intake. Probiotic Bacillus given every two days eliminated S. aureus in the guts of the mice. The same test using Bacillus where fengycin production had been removed had no effect, and S. aureus grew as expected. This is one of the first study that provide human evidence supporting the biological significance of probiotic bacterial interference and show that such interference can be achieved by blocking a pathogen’s signaling system. Continue reading

Government Agencies Provide Funding For Most USPSTF Evidence Reviews

MedicalResearch.com Interview with:

Jennifer Villani, PhD, MPH Office of Disease Prevention National Institutes of Health

Dr. Villani

Jennifer Villani, PhD, MPH
Office of Disease Prevention
National Institutes of Health

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

Response: The US Preventive Services Task Force (USPSTF) develops recommendations for the delivery of clinical preventive services based on the highest quality scientific evidence available. We performed a comprehensive assessment of the sources of funding for the research studies in this evidence base.

The results showed that government agencies supported the most articles (56%), with the remaining support coming from nonprofits or universities (32%), and industry (17%). The National Institutes of Health was the single largest funder of research articles underlying the USPSTF recommendations.  Continue reading

Genetic Cause of Cushing’s Disease Detected

MedicalResearch.com Interview with:

Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda

Dr. Stratakis

Constantine A. Stratakis, MD, DMSci
Section on Endocrinology and Genetics
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health, Bethesda 

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

Response: The pituitary and adrenal glands operate on a kind of feedback loop.  In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol.  Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease.

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Therapeutic Hypothermia After In-Hospital Cardiac Arrest in Children

MedicalResearch.com Interview with:

Victoria Pemberton, RNC, MS, CCRC Program Officer Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute, NIH Bethesda, Maryland

Victoria Pemberton

Victoria Pemberton, RNC, MS, CCRC
Program Officer
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute, NIH
Bethesda, Maryland

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

  • Previous studies have examined cardiac arrest when it occurs outside of the hospital in both children and adults, with current guidelines recommending hypothermia (body cooling) or normothermia (maintenance of normal body temperature) after such an arrest.   This trial addresses pediatric cardiac arrest in a hospital setting, for which no previous data existed. Because children who experience an in-hospital cardiac arrest differ significantly from children who arrest outside of the hospital, it is important to test these treatments in this population.
  • The trial found no significant differences in survival and neurobehavioral functioning a year after cardiac arrest between children assigned to the hypothermia arm and those assigned to normothermia.

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Premature Midlife Deaths Increase in US Whites and Native Americans

Dr. Meredith Shiels

Dr. Meredith Shiels

MedicalResearch.com Interview with:
Dr Meredith S Shiels

Division of Cancer Epidemiology and Genetics
National Cancer Institute
Bethesda, MD

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

Response: In most high-income countries, premature death rates have been declining, due to the overwhelming successes of public health efforts to prevent and treat chronic disease. The US is a major outlier, where death rates overall have plateaued, or even increased, as reported recently by our sister agency, the Centers for Disease Control and Prevention. Of particular concern are recent reports of increasing death rates among Americans during mid-life.

To expand upon prior findings, we focused on premature death, which we defined as death occurring between the ages of 25 and 64. We examined finely detailed death certificate data for the entire U.S. population and described changes in death rates during 1999-2014 by cause of death, sex, race, ethnicity, and geography. To provide context to our findings, we compared trends in death rates in the U.S. to England and Wales and Canada.

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Genes Linked To Ectopic Fat Deposition Identified

MedicalResearch.com Interview with:

Audrey Chu, Ph.D. Division of Intramural Research of the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health

Dr. Audrey Chu

Audrey Chu, Ph.D.
Division of Intramural Research
National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health

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

Response: Body shape reflects the underlying adipose tissue distributed throughout different compartments of the body (ectopic fat). Variation in ectopic fat is associated with diabetes, hypertension and heart disease. This is mostly independent of overall adiposity. Ectopic fat can be measured using special x-rays procedures such as CT (“CAT scans”) or MRI and can give more information about fat distribution. Fat distribution characteristics can run in families, suggesting that a person’s genes can help determine the amount of fat that can accumulate in different parts of the body. Identifying genes that are associated with ectopic fat can provide insight into the biological mechanisms leading to differences in cardiometabolic disease risk.

In order to understand which genes might be involved, we examined genetic variants across the genome and their association with ectopic fat in the largest study of its kind including over 18,000 individuals of four different ancestral backgrounds.

Several new genetic regions were identified in association with ectopic fat in addition to confirming previously known regions. The association of the new regions was specific to ectopic fat, since the majority of the regions were not associated with overall or central adiposity. Furthermore, most of these regions were not associated with type 2 diabetes, lipids, heart disease or blood pressure. The major exception was the region surrounding the UBE2E2 gene, which was associated with diabetes.

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Nausea and Vomiting During Pregnancy May Signal Less Risk of Pregnancy Loss

MedicalResearch.com Interview with:
Stefanie N. Hinkle, Ph.D.

Staff Scientist | Epidemiology Branch
Division of Intramural Population Health Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health

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

Response: Thank you for the interest in our research. Nausea and vomiting are very common early in pregnancy and these symptoms can be difficult for women. Before we began this study there was very limited high-quality data on the implications of these difficult symptoms in pregnancy. Our study is unique because we asked women to report their symptoms continuously throughout their pregnancy before they may or may not have gone on to have a loss. We found that among women with 1 or 2 prior pregnancy losses, women who have nausea, and particularly nausea with vomiting, were less likely to have a pregnancy loss.

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BDNF Is Potential Biomarker For Autism Spectrum Disorder

MedicalResearch.com Interview with:

Dr. Yong Cheng, PhD Postdoctoral Fellow NIH

Dr. Yong Cheng

Dr. Yong Cheng, PhD
Postdoctoral Fellow
NIH

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

Response: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders which affect about 1 in 68 children in the United States, according to data from the Centers for Disease Control and Prevention. Brain-derived neurotrophic factor (BDNF) is an important moderator in neurodevelopment and neuroplasticity, and studies have suggested the involvement of BDNF in ASD. Although some clinical studies show abnormal expression of BDNF in children with ASD, findings have been inconsistent. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood BDNF levels in children with ASD, compared with healthy peers.

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Marijuana Use Doubles From 2002-2014

MedicalResearch.com Interview with:

Dr. Wilson Compton MD, Deputy Director National Institute on Drug Abuse

Dr. Wilson Compton

Dr. Wilson Compton MD, Deputy Director
National Institute on Drug Abuse

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

Response: The study found that overall past year marijuana use by adults in the U.S. increased by more than 30% in the past dozen years, and 10 million more people were using marijuana in 2014 than in 2002. Use of marijuana on a daily (or near daily) basis increased even more markedly. In 2002, 3.9 million adults in the U.S. reported using marijuana daily or nearly every day, and the number more than doubled to 8.4 million by 2014. Along with this increase in use, we found that U.S. adults perceptions of the potential harms from using marijuana greatly decreased. Despite scientific evidence of potential harms, adults are much less convinced about dangers associated with using marijuana. These reductions in perceived harm were strongly associated with the increases in use.

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Coronary CT Angiography Can Detect Soft Coronary Plaque In Asymptomatic Patients

David A. Bluemke, MD, PhD, MsB, FAHA, FACR Director Radiology and Imaging Sciences Senior Investigator, National Institute of Biomedical Imaging and Bioengineering Adjunct Investigator,  NLBI, NIDDKMedicalResearch.com Interview with:
David A. Bluemke, MD, PhD, MsB, FAHA, FACR
Director Radiology and Imaging Sciences
Senior Investigator,
National Institute of Biomedical Imaging and Bioengineering
Adjunct Investigator,  NLBI, NIDDK

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

Dr. Bluemke: Most knowledge about the extent of coronary disease is from high risk patients who have coronary angiograms. Yet most individuals are symptomatic and have lower cardiovascular risk, and would not undergo a coronary angiogram.

Coronary CT angiography can be used to evaluate the extent of plaque in low or moderate risk individuals. The most concerning type of plaque is “soft plaque”, which can increase or rupture over time.

Using coronary CT, all coronary plaque throughout the entire heart was measured. Importantly, the amount of soft plaque was uniquely associated with risk factors such as LDL, diabetes, and hypertension.

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Low Risk Prostate Cancer: Panel endorses active monitoring

An independent panel convened this week by the National Institutes of Health has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies—such as active surveillance—have not been uniformly studied and available data do not yet point to clear follow-up protocols. The panel recommended standardizing definitions and conducting additional studies to clarify which monitoring strategies are most likely to optimize patient outcomes.

“It’s clear that many men would benefit from delaying treatment, but there is no consensus on what constitutes observational strategies and what criteria should be used to determine when treatment might ultimately be needed among closely-monitored men,” said Dr. Patricia A. Ganz, conference panel chairperson and director of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center at the University of California in Los Angeles.

Prostate cancer is the most common non-skin cancer in men in the United States. It is estimated that in 2011, approximately 240,000 men will be newly diagnosed with prostate cancer and 33,000 will die of the disease. More than half of these cancers are localized (confined to the prostate), not aggressive at diagnosis, and unlikely to become life-threatening. However, approximately 90 percent of patients receive immediate treatment, such as surgery or radiation therapy. For many of these patients, treatment has substantial short- and long-term side effects, such as diminished sexual function and loss of urinary control, without clear benefits, such as improved survival. Identifying appropriate management strategies for different subgroups of patients is critical to improving survival and reducing the burden of adverse effects.

Currently, clinicians often describe two alternatives to immediate treatment of low-risk prostate cancer: observation with and without the intent to cure. Observation without intent to cure, sometimes referred to as watchful waiting, is a passive approach, with treatment provided to alleviate symptoms if they develop. Observation with intent to cure, often referred to as active surveillance, involves proactive patient follow-up in which blood samples, digital rectal exams, and repeat prostate biopsies are conducted on a regular schedule, and curative treatment is initiated if the cancer progresses.

The panel identified emerging consensus in the medical community on a definition for low-risk prostate cancer: a prostate-specific antigen (PSA) level less than 10 ng/mL and a Gleason score of 6 or less. Using this definition, the panel estimated that more than 100,000 men diagnosed with prostate cancer each year would be candidates for active monitoring rather than immediate treatment. Importantly, however, the panel found that protocols to manage active monitoring still vary widely, hampering the evaluation and comparison of research findings.

Prostate cancer affects some 30-40 percent of men over the age of 50. Some of these men will benefit from immediate treatment, others will benefit from observation. We need to standardize definitions, group patients by their risks, and conduct additional research to determine the best protocols for managing low-risk disease, stated Dr. Ganz.

The panel further recommended that disease terminology should be refined as a result of changes in the patient population with prostate cancer due to prostate-specific antigen (PSA) testing. Because of the very favorable prognosis of PSA-detected, low-risk prostate cancer, the panel recommended that strong consideration be given to removing the anxiety-provoking term “cancer” for this condition.

The panel also found that clinicians’ framing of disease management options is an important factor in patient decision-making. Other influential factors include views of family members, cancer experiences of family and friends, lifestyle priorities, and personal philosophy. Findings from studies in communication sciences and behavioral economics could be applied in clinical settings to promote informed, shared decision-making. While research continues to fill knowledge gaps and develop consensus, the decisions faced by men and their providers following a diagnosis of localized, low-risk prostate cancer should be highly individualized, and include the consideration of biological, psychological, social, and cultural factors.

With regard to future research, the panel recommended against future federal funding for single-institutional site studies, and emphasized instead the importance of supporting multisite clinical research studies. The panel also supports the establishment of registry-based cohort studies that collect longitudinal data on active monitoring participants, including clinical and patient-reported outcomes.

The state-of-the-science conference was sponsored by the NIH Office of Medical Applications of Research, the National Cancer Institute, and the Centers for Disease Control and Prevention, along with other NIH and U.S. Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.

The 14-member state-of-the-science panel included experts in the fields of cancer prevention and control, urology, pathology, epidemiology, genetics, transplantation, bioethics, economics, health services research, shared decision-making, health communication, and community engagement. A complete listing of the panel members and their institutional affiliations is included in the draft conference statement.

In addition to the material presented at the conference by speakers and the comments of conference participants presented during discussion periods, the panel considered pertinent research from the published literature and the results of a systematic review of the literature. The systematic review was prepared through the Agency for Healthcare Research and Quality Evidence-based Practice Centers (EPC) program by The Tufts Medical Center Evidence-based Practice Center. The EPCs develop evidence reports and technology assessments based on rigorous, comprehensive syntheses and analyses of the scientific literature, emphasizing explicit and detailed documentation of methods, rationale, and assumptions. A link to the evidence report on the role of active surveillance in the management of men with localized prostate cancer is available at http://consensus.nih.gov/2011/prostate.htm.

The panel’s statement is an independent report and is not a policy statement of the NIH or the Federal Government. The NIH Consensus Development Program was established in 1977 as a mechanism to judge controversial topics in medicine and public health in an unbiased, impartial manner.