Significant Amount of Medical Literature Contaminated With Misidentified Cells

MedicalResearch.com Interview with:

Serge Horbach MSc Institute for Science in Society Radboud University Nijmegen

Serge Horbach

Serge Horbach MSc
Institute for Science in Society
Radboud University Nijmegen
 

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

Response: Since the late 60s, researchers have pointed to issues in biomedical research stemming from the misidentification of cells. Starting with controversy around HeLa cells, researchers became aware of cells invading other cell cultures. Currently, 488 cell lines have become mixed up with the wrong cells, still often HeLa cells. This leads to errors in reporting research. For example, some research papers have reported results for “lung cancer cells” that turned out to be liver cancer cells, or even mouse cells.

We wanted to know what happened to past research and set out to estimate the number of scientific publications affected by misidentified cells. By tracing misidentified cells of the ICLAC database in Web of Science, we found 32.755 contaminated publications, or 0,8% of all literature in cell biology. These articles are cited by at least 500.000 other publications.

More worryingly, it turned out that this problem is highly stubborn. Currently, still a few dozen new articles are published every month reporting on other cells than were actually used, leading to a total of 1200 each year. And this number is not decreasing, in spite of a database of misidentified cells, of genetic testing availability, requirements by some prominent journals, or attention for the problem in the literature. We were also able to establish that this is not just a problem for newly emergent countries in the international research community, but also for countries with well-establishments research traditions. In spite of great efforts, the problem of cell misidentification is not at all solved.

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High Blood Pressure Is a Risk Factor For Mitral Regurgitation

MedicalResearch.com Interview with:

Professor Kazem Rahimi, FRCP MD DM MSc FES Deputy Director, The George Institute for Global Health UK Associate Professor of Cardiovascular Medicine, University of Oxford Honorary Consultant Cardiologist, Oxford University Hospitals NHS Trust

Dr. Rahimi

Professor Kazem Rahimi, FRCP MD DM MSc FES
Deputy Director, The George Institute for Global Health UK
Associate Professor of Cardiovascular Medicine, University of Oxford
Honorary Consultant Cardiologist, Oxford University Hospitals NHS Trust 

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

Response: Mitral regurgitation, the most common heart valve disorder in high-income countries, has until now been considered a degenerative disorder, which results from damage over time due to ‘wear and tear’. As a result, the focus of medical practitioners has been on treating the disorder – by repairing or replacing the valve – rather than preventing it. This is partly because there has been a lack of large-scale, longitudinal studies investigating the effect of risk factors on the condition.

We set out to analyse data on 5.5 million patients in the UK over 10 years. Our findings show, for the first time, that elevated blood pressure is an important risk factor for mitral regurgitation. Consistent with prior evidence on blood pressure associations with other cardiovascular disease – such as stroke and heart attacks – we found an association with mitral regurgitation that is continuous across the whole spectrum of blood pressure. More specifically, every 20 mmHg higher baseline systolic blood pressure is associated with a 26% increased risk of mitral regurgitation, with no threshold below or above which this relationship is not true.

The association we found was only partially mediated by conditions that are established causes of secondary mitral regurgitation, which suggests that high blood pressure has a direct and independent effect on valve degeneration.

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Complexity of Animals Depends On Diverse Patterns of Gene Regulation

MedicalResearch.com Interview with:
Colin Sharpe

School of Biology
Institute of Biomolecular and Biomedical Science
School of Biological Sciences
University of Portsmouth
Portsmouth, United Kingdom 

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

Response: We have long been fascinated by the question of what underpins the increasing complexity of multicellular animals. In a recent publication we looked at changes to the diversity of the NCoR family corepressors (NCoRs) across the Deuterostomes and found an increase in diversity from sea urchins to humans (1). This is due to gene duplication, an increase in alternative splicing and the encorporation of more protein motifs and domains.

In this study we devised a measure of functional diversity based on these three factors and calculated this value for over 12000 genes involved in transcription in nine species from the nematode worm to humans. Orthologues whose increase in diversity correlated with the increase in complexity of these animals were then selected and we looked for common features and interactions between the selected genes.

We found that proteins that regulate the dynamic organisation of chromatin were significantly enriched within the selection.

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Genetic Variants Demonstrate Humans Continue To Evolve Through Natural Selection

MedicalResearch.com Interview with:

Hakhamanesh Mostafavi, MS PhD student Department of Chemical Engineering Columbia University

Mostafavi Hakhamanesh

Hakhamanesh Mostafavi, MS
PhD student
Department of Biological Sciences
Columbia University 

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

Response: We know very little about the genetic variants that underlie adaptation in humans. This is in part because we have mostly been limited to methods that search for footprints of ancient selection (that has acted for over thousands to millions of years) in the genomes of present-day humans; so by design are indirect and make strong assumptions about the nature of selection.

These days, thanks to advances in genomic technologies, genetic data for large numbers of people is being collected, mostly for biomedical purposes. Accompanied by information on survival and reproductive success of these individuals, such large datasets provide unprecedented opportunities for more direct ways to study adaptation in humans.

In this work, we introduced an approach to directly observe natural selection ongoing in humans. The approach consists in searching for mutations that change in frequency with the age of the individuals that carry them, and so are associated with survival. We applied it to around 210,000 individuals from two large US and UK datasets.

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Similar Signaling Pathways Trigger Anxiety In Variety of Species

MedicalResearch.com Interview with:

Yuanyuan Xie, PhD Postdoctoral Researcher Department of Neuroscience University of Pennsylvania Philadelphia, PA 19104

Dr.Yuanyuan Xie

Yuanyuan Xie, PhD
Postdoctoral Researcher
Department of Neuroscience
University of Pennsylvania
Philadelphia, PA 19104

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

Response: I joined Dr. Richard Dorsky’s lab in mid 2013 after a lab switch toward the end of the fourth year in my PhD. By then, the Dorsky lab at the University of Utah had published zebrafish lef1 mutants with a hypothalamic neurogenesis phenotype. I was asked to perform an RNA-sequencing (RNA-seq) experiment to identify Lef1-dependent genes. In doing so, I also characterized the cellular phenotype in the hypothalamus of our zebrafish mutants in a greater detail.

The first transition of this project happened when I proposed in late 2013 to test whether Lef1’s function was conserved in the mouse hypothalamus. Dr. Dorsky liked that idea, but told me that I could only pursue that idea if there was a Lef1-flox mouse strain available, because he did not want me to delay my graduation after a lab switch by making a new mouse line. Fortunately, a quick google search located the right mouse line published from the group of Dr. Hai-Hui Xue, who was generous enough to share some mice with us. Because the Dorsky lab was a zebrafish lab by then, we collaborated with Dr. Edward Levine to maintain our mice under his animal protocol. I was initially trained by Dr. Levine and his lab specialist Anna Clark for general mouse colony management. After Dr. Levine moved to Vanderbilt University in early 2016, we began to maintain our mice under Dr. Camille Fung’s animal protocol. Dr. Dorsky also supported me in attending a 3-week Cold Spring Harbor Laboratory Course on Mouse Development, Stem Cells & Cancer in mid 2015, which made me much more confident in handling mouse work afterwards.

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How Much Does Mother’s BMI Influence Children’s Metabolic Health?

MedicalResearch.com Interview with:

Prof. Deborah A Lawlor MSc(Lond), MBChB, PhD(Bristol), MPH(Leeds), MRCGP, MFPHM Professor of Epidemiology MRC Integrative Epidemiology Unit at the University of Bristol NIHR Bristol Biomedical Research Centre Population Health Sciences, Bristol Medical School Oakfield House, Oakfield Grove, Bristol

Prof. Lawlor

Prof. Deborah A Lawlor
MSc(Lond), MBChB, PhD(Bristol), MPH(Leeds), MRCGP, MFPHM
Professor of Epidemiology
MRC Integrative Epidemiology Unit at the University of Bristol
NIHR Bristol Biomedical Research Centre
Population Health Sciences, Bristol Medical School
Oakfield House, Oakfield Grove, Bristol

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

Response: As the obesity epidemic has occurred there has been increasing concern about pregnant women being more adipose (having higher levels of fat) during their pregnancy. One particular concern is that women who are on average fatter will have more extreme changes in pregnancy on their lipid, fatty acid, amino acid and glucose levels. In normal ‘healthy’ pregnancy these metabolites increase during pregnancy as part of the physiological response to pregnancy which ensures that the developing fetus has sufficient fuel (nutrients – fats, proteins, sugars) for healthy growth and development. Women who are more adipose tend to have a more extreme change in these fuels and as a consequence the developing fetus is ‘overfed’. There is a linear relationship between a pregnant woman’s body mass index and her infants birth weight, such that each increment greater adiposity (body mass index) of the mother there is on average and increment greater infant birth weight.

Recently, using a method that uses genetic variants (Mendelian randomization) we have shown that this association is likely to be causal (JAMA 2016). But whether there is a lasting effect on offspring health of being overfed in the uterus is unknown. There are concerns that there will be a lasting effect and that for daughters of more adipose women, this would mean that they go into their pregnancies on average fatter and with higher levels of the metabolites that could then overfeed their developing fetus. If this were the case it would mean the obesity epidemic could be accelerated across generations.

There are associations of mothers body mass index with later offspring body mass index, BUT this might not be anything to do with developmental overfeeding of the feeding in the uterus – it could simply reflect shared lifestyles that offspring adopt from their mother (and father) or shared genetic effects. In this study we tried to separate out whether there was evidence for a long-term offspring effect on their lipids, fatty acids, amino acids, glucose, and an inflammatory marker, of having a mother who was on average fatter during her pregnancy that was due to overfeeding in the uterus, as opposed to shared family lifestyle and genetics. We did this by comparing associations of mothers pre-pregnancy BMI with offspring outcomes to the same associations of fathers pre-pregnancy BMI with the same outcomes.

Our assumption here was that fathers BMI could not directly result in overfeeding of the fetus and so if the associations were similar this would suggest that they were largely driven by family factors.

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Evidence Does Not Support Gabapentinoids in Non-Specific Chronic Low Back Pain

MedicalResearch.com Interview with:

Harsha Shanthanna MBBS, MD, MSc Associate Professor, Anesthesiology Chronic Pain Physician St Joseph's Healthcare,McMaster University Hamilton, Canada Diplomate in National Board, Anesthesiology (India) Fellow in Interventional Pain Practice (WIP) European Diplomate in Regional Anesthesia and Pain (ESRA)

Dr. Shanthanna

Harsha Shanthanna MBBS, MD, MSc
Associate Professor, Anesthesiology
Chronic Pain Physician
St Joseph’s Healthcare,McMaster University
Hamilton, Canada
Diplomate in National Board, Anesthesiology (India)
Fellow in Interventional Pain Practice (WIP)
European Diplomate in Regional Anesthesia and Pain

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

Response: Pregabalin (PG) and gabapentin (GB) are increasingly used for nonspecific Chronic Low Back Pain (CLBP) despite a lack of evidence. There have been concerns expressed over their increased prescribing for various non cancer pain indications in recent years. Their use requires slow titration to therapeutic doses and establishing maintenance on a long-term basis. With prolonged treatment, the potential gain over possible adverse effects and risks could become unclear.

We searched Cochrane, MEDLINE and EMBASE databases for randomized control trials reporting the use of gabapentinoids for chronic lower back pain treatment of 3 months or more in adult patients.

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Cadmium in Shellfish and Smoking Linked to Endometrial Cancer

MedicalResearch.com Interview with:

Jane McElroy, Ph.D. Associate professor Department of Family and Community Medicine MU School of Medicine

Dr. McElroy

Jane McElroy, Ph.D.
Associate professor
Department of Family and Community Medicine
MU School of Medicine

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

Response: More than 31,000 new cases of endometrial cancer are expected to be diagnosed in 2017. Through a five-year observational study, we found that women with increased levels of cadmium had an increased risk of endometrial cancer. Cadmium is a metal commonly found in foods such as kidneys, liver and shellfish as well as tobacco It’s a finding we hope could lead to new treatments or interventions to prevent the fourth most common cancer in women.

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Blood Biomarkers Signal Multiple Organ Dysfunction Syndrome After Critical Injuries

MedicalResearch.com Interview with:

Dr. Joanna Shepherd Centre for Trauma Sciences Blizard Institute Queen Mary, University of London

Dr. Shepherd

Dr. Joanna Shepherd
Centre for Trauma Sciences
Blizard Institute
Queen Mary, University of London

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

Response: Recent advances in resuscitation and treatment of life-threatening critical injuries means that patients with previously unsurvivable injuries are now surviving to reach hospital.  However, many of these patients develop Multiple Organ Dysfunction Syndrome (MODS), which is a failure of several organs including the lung, heart, kidney, and liver.

We studied immune cell genes in the blood of critically injured patients within the first few minutes to hours after injury, a period called the ‘hyperacute window’. We found a small and specific response to critical injury during this window that then evolved into a widespread immune reaction by 24 hours.  The development of MODS was linked to changes in the hyperacute window, with central roles for innate immune cells (including natural killer cells and neutrophils) and biological pathways associated with cell death and survival.  By 24 hours after injury, there was widespread immune activation present in all critically injured patients, but the MODS signal had either reversed or disappeared.

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Menopause Facilitates Transmission of Cognitive Resources To Grandchildren

MedicalResearch.com Interview with:

“Grandmother” by Joe Shlabotnik is licensed under CC BY 2.0

“Grandmother” by Joe Shlabotnik

Carla Aimé PhD
Institute of Evolutionary Sciences of Montpellier
France

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

Response:  In all human populations, regardless of environmental and socioeconomic conditions, menopause occurs in women well before the end of their expected lifespan. Conversely, extensive post-reproductive life-span is rare in other species; except in some cetaceans. Evolutionary theory predicts that menopause and extensive post-reproductive lifespan should emerge and persist in populations only if it is advantageous for gene transmission. Identifying this advantage is a long-standing issue, and some hypotheses has already been suggested by other researchers. However, testing these hypotheses about the emergence of menopause is difficult, in particular because menopause exists today in all human populations. It is thus not possible to measure in real life the evolutionary advantage related to menopause by comparing gene transmission of women who stop reproduction and women who don’t stop reproduction. Here, we used computer simulations to overcome this difficulty by modeling the emergence of menopause in simulated human populations.

The main finding were the following :

– Physiological constraints are not required for menopause to emerge.

– The increasing cost of reproduction with age cannot explain menopause.

– Grandmothering is part of the process leading to menopause : stopping reproduction allow reallocating resources to existing children and grand-children, thus leading to increase gene transmission via increased fertility of children and survival of grand children

– Cognitive resources are also important. Indeed, cognitive abilities allow accumulation of skills and experience over the lifespan, thus providing an advantage for resource acquisition. These surplus resources can then be used to increase the number of offspring or be transmitted to existing offspring and grandoffspring. Stopping reproduction during aging allows allocating more resources to assist offspring and grandoffspring, thus increasing children’s fertility and grandchildren’s survival.

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How Does HPV Virus Lead To Skin Cancer?

MedicalResearch.com Interview with:
Prof. Dr. med. Sigrun Smola
Institute of Virology, Saarland University
Homburg/Saar, Germany

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

Response: Non-melanoma skin cancer (NMSC), the most common cancer in humans, is caused by UV-irradiation. The potential co-factor role of cutaneous genus beta-human papillomaviruses (beta-HPV) in skin carcinogenesis, particularly in immunosuppressed patients, has become a major field of interest. However, the underlying mechanisms were unclear.

The skin has natural mechanisms providing protection against UV-induced damage. One important factor suppressing UV-induced skin carcinogenesis is the transcription factor C/EBPα belonging to the CCAAT/enhancer binding protein family. C/EBPα can induce cellular differentiation and is regarded as a tumor suppressor in various tissues. When C/EBPα expression is blocked in these tissues, tumorigenesis is enhanced.

Another important factor is the microRNA-203. It has been shown to control “stemness” in normal skin by suppressing a factor called p63. In many tumors miR-203 expression is shut off releasing this “brake”.

In our study we demonstrate that cutaneous beta-HPV interferes with both protective factors providing an explanation how cutaneous beta-HPV enhances the susceptibility to UV-induced carcinogenesis. Moreover, we provide evidence that these viruses regulate miR-203 via C/EBPα.

We have investigated this mechanism in Epidermodysplasia verruciformis (EV) patients that serve as a human model disease for studying the biology of genus beta-HPVs. They are highly susceptible to persistent genus beta-HPV infection, such as HPV8, and have an increased risk to develop non-melanoma skin cancer at sun-exposed sites.

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If High School Students Are Naturally Owls, Shouldn’t School Start Later?

MedicalResearch.com Interview with:
Dr. Dorothee Fischer
Department of Environmental Health
Harvard T.H. Chan School of Public Health, Boston, Massachusetts
Center for Injury Epidemiology, Liberty Mutual Research Institute for Safety
Hopkinton, Massachusetts,

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

Response: Chronotypes are a result of how the circadian clock embeds itself into the 24h light-dark cycle, producing earlier and later individuals (“larks and owls”) with regards to rhythms in physiology, cognition and behavior, including sleep.

It can be beneficial for health and safety to sync forced wake times (work, school) with individual chronotypes, thereby reducing the misalignment between sleep, circadian rhythms and external demands.

To better inform potential interventions such as tailored work schedules, more information is needed about the prevalence of different chronotypes and how chronotype differs by age and sex.

To the best of our knowledge, this is the first large-scale and nationally representative study of chronotypes in the US.
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Heroin Epidemic Costs US Over $50 Billion Per Year

MedicalResearch.com Interview with:

A. Simon Pickard, PhD

Dr. Pickard

A. Simon Pickard, PhD
Professor, Dept of Pharmacy Systems, Outcomes and Policy
University of Ilinois at Chicago
College of Pharmacy

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

Response: The heroin epidemic, which has left virtually no part of American society unscathed, can be viewed as an illness.  Unlike some illnesses, however, it was largely manufactured by stakeholders in the healthcare system, wittingly or unwittingly.

The main finding, that heroin addiction costs us just over $50 billion per year, is likely a conservative estimate.

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Opioid Agonist Therapy Found Cost Effective In Preventing HIV in People Who Inject Drugs

MedicalResearch.com Interview with:

Cora Bernard, MS, PhD candidate Pre-doctoral Student in Management Science and Enginnering Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research Stanford Health Policy

Cora Bernard

Cora Bernard, MS, PhD candidate
Pre-doctoral Student in Management Science and Enginnering
Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research
Stanford Health Policy

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

Response: The US opioid epidemic is leading to an increase in the US drug-injecting population, which also increases the risks of HIV transmission. It is critical to public health that the US invests in a coherent and cost-effective suite of HIV prevention programs. In our model-based analysis, we considered programs that have the potential both to prevent HIV and to improve long-term health outcomes for people who inject drugs. Specifically, we evaluated opioid agonist therapy, which reduces the frequency of injection; needle and syringe exchange programs, which reduce the frequency of injecting equipment sharing; enhanced HIV screening and antiretroviral therapy programs, which virally suppress individuals and decrease downstream transmission; and oral HIV pre-exposure prophylaxis (PrEP), which is taken by an uninfected individual and lowers the risk of infection.

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Older Maternal Age Continues To Be Increased Risk Factor For Adverse Outcomes

Sarka Lisonkova, MD, PhD Assistant Professor, Department of Obstetrics and Gynaecology, University of British Columbia. Children’s and Women’s Health Centre

Dr. Lisonkova

MedicalResearch.com Interview with:
Sarka Lisonkova, MD, PhD

Assistant Professor,
Department of Obstetrics and Gynaecology,
University of British Columbia.
Children’s and Women’s Health Centre

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

Response: Adverse fetal and infant outcomes associated with maternal age were known and our study confirms that the risk of fetal and neonatal death and severe neonatal morbidity increases among mothers over 30 years. We also knew that older mothers are more likely to have hypertension, diabetes, and other chronic diseases, and they are more likely to develop gestational diabetes, hypertension during pregnancy, and preeclampsia. These complications may put the fetus or newborn at risk, but are generally not considered to be potentially life threatening to the mother. Our study adds new information on the rates of severe maternal morbidities that have a high case-fatality rate, lead to organ damage, or have serious health implications such as hysterectomy. Our study also adds the information on the rates of any severe adverse birth outcome – for baby or mom – in the association with maternal age, which is important for counseling. Women usually want to know ‘what are the chances that anything bad happens’.

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Vitamin D Supplements Will Probably Not Help Asthma or Atopic Dermatitis

MedicalResearch.com Interview with:

Brent Richards, MD, MSc</strong> Associate Professor of Medicine William Dawson Scholar / FRQS Clinical Research Scholar Departments of Medicine, Human Genetics, Epidemiology and Biostatistics McGill University Senior Lecturer, King's College London (Honorary)

Dr. Brent Richards

Brent Richards, MD, MSc
Associate Professor of Medicine
William Dawson Scholar / FRQS Clinical Research Scholar
Departments of Medicine, Human Genetics, Epidemiology and Biostatistics McGill University
Senior Lecturer, King’s College London (Honorary)

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

Response: Some previous epidemiological studies have suggested that low vitamin D levels are associated with increased rates of asthma, atopic dermatitis—an itchy inflammation of the skin—and elevated levels of IgE, an immune molecule linked to atopic disease (allergies). In our study, we looked at genetic and health data on more than 100,000 individuals from previous large studies to determine whether genetic alterations that are associated with vitamin D levels predispose people to the aforementioned conditions.

We found no statistically significant difference between rates of asthma (including childhood-onset asthma), atopic dermatitis, or IgE levels in people with and without any of the four genetic changes associated with lower levels of 25-hydroxyvitamin D, the form of vitamin D routinely measured in the blood.

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Arsenic Still Found In Infant Rice Products

MedicalResearch.com Interview with:

Dr. Antonio J. Signes-Pastor, PhD Institute for Global Food Security Queen’s University Belfast Belfast, Northern Ireland, United Kingdom, Department of Epidemiology, Geisel School of Medicine Dartmouth College Lebanon, NH

Dr. Signes-Pastor

Dr. Antonio J. Signes-Pastor, PhD
Institute for Global Food Security
Queen’s University Belfast
Belfast, Northern Ireland, United Kingdom,
Department of Epidemiology, Geisel School of Medicine
Dartmouth College Lebanon, NH

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

Response: Inorganic arsenic is a human carcinogen, which has also been associated with several adverse health effects including neurological, cardiovascular, respiratory, and metabolic outcomes. Early life exposure is of particular concern since it may adversely impact on lifetime health outcomes. If low inorganic arsenic drinking water is available the main source of exposure is the diet, especially rice and rice-based products, which are widely used during weaning and to feed infants and young children. In order to reduce exposure, the EU has recently regulated (1st January 2016) the inorganic arsenic maximum level of 0.1 mg/kg for rice products addressed to infants and young children. This level is also under consideration by the US FDA.

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Fresh Fruit Consumption May Lower Risk of Diabetes and Vascular Complications

MedicalResearch.com Interview with:
Huaidong Du

Senior Research Fellow
China Kadoorie Biobank
Medical Research Council Population Health Research Unit
Clinical Trial Service Unit & Epidemiological Studies Unit
Nuffield Department of Population Health
Oxford UK

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

Response: This research article describes findings from the China Kadoorie Biobank study which is a large population based prospective cohort study including about 0.5 million adults recruited from 10 areas in China.

The main reason for us to perform this study is because previous evidence on potential benefit of fruit consumption in diabetes prevention and management is very limited. The sugar content of fruit has led to concerns in many parts of the world (e.g. China and several other Asian countries) about its potential harm for people with (high risk of) diabetes. This has consequently Chinese people diagnosed with diabetes tend to restrict their fruit intake. With the rapid increase of diabetes incidence in China and many other Asian countries, it is critically important to investigate the associations of fruit consumption with the incidence diabetes and, among those with diabetes already, diabetic macro- and microvascular complications.

Through analysing data collected during 7 years of follow-up, the study found that people who eat fresh fruit more frequently are at lower risk of developing diabetes and diabetes related vascular complications. Compared with non-consumers, those who ate fresh fruit daily had a 12% lower risk of developing diabetes. Among participants with diabetes at the start of the study, higher fresh fruit consumption also showed health benefits, with a 100g portion of fruit per day associated with 17% lower overall mortality, 13% lower risk of developing diabetes-related complications affecting large blood vessels (e.g. ischaemic heart disease and stroke) and 28% lower risk of developing complications affecting small blood vessels (e.g. kidney and eye diseases).

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

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

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

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

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

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Human Behavioral Complexity Peaks At Age 25

MedicalResearch.com Interview with:
Dr. Hector Zenil

Co-director
Information Dynamics Lab
Unit of Computational Medicine, SciLifeLab
Center for Molecular Medicine
Karolinska Institute, Stockholm, Sweden 

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

Response: The generation of randomness is known to be related to cognitive abilities. It has also recently been shown that animals can recur to random behaviour to outsmart other animals or overcome certain situations. Our results that humans can best outsmart computers in generating randomness at a certain age (25). The results correspond to what it was suspected, that cognitive abilities peak at an early age before declining and that no other factor was important.

We quantified a type of mathematical randomness that is known to be the true type of randomness as opposed to e.g. ‘statistical randomness’. Something that is random is difficult to describe in a succinct way. Unlike ‘statistical randomness’, ‘algorithmic randomness’ does not only produce something that appears random but also that is very difficult to generate or produce. Conversely, something that may look random for the standard of statistical randomness may not turn out to be truly random.

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Vitamin D Deficiency Highly Prevalent in Pediatric Irritable Bowel Syndrome

MedicalResearch.com Interview with:

Benjamin Udoka Nwosu, MD, FAAP Associate Professor of Pediatrics Division of Endocrinology University of Massachusetts Medical School Worcester, Massachusetts

Dr. Nwosu

Benjamin Udoka Nwosu, MD, FAAP
Associate Professor of Pediatrics
Division of Endocrinology
University of Massachusetts Medical School
Worcester, Massachusetts

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Vitamin D deficiency has been reported in various gastrointestinal disorders but the vitamin D status of children and adolescents with irritable bowel syndrome (IBS) has not been previously characterized.

Secondly, the vitamin D status in IBS has not been compared to those of other malabsorption syndromes such as irritable bowel syndrome, lactose intolerance, and celiac disease.

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No Decrease In Incidence of Dementia Over Past Decades

MedicalResearch.com Interview with:

Emma van Bussel MD, MSc Academic Medical Center | University of Amsterdam Amsterdam | The Netherlands

Dr. Emma van Bussel

Emma van Bussel MD, MSc
Academic Medical Center | University of Amsterdam
Amsterdam | The Netherlands 

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

Response: Dementia forms a high social and economic burden on society. Since there is a growing number of older people, the occurrence of dementia is expected to increase over the years to come. For future planning of care, it is important to have reliable predictions on new dementia cases for the population at large. Studies in Western countries suggested that the incidence per 1000 person years is declining.

We studied the incidence trend of dementia in the Netherlands in primary care registry data, in a population of over 800,000 older people (60 years and over) for the years 1992 to 2014. Our results indicate a small increase of 2.1% (95% CI 0.5% to 3.8%) per year in dementia incidence over the past decades. The trend did not change in the years after 2003, when a national program was developed to support dementia care and research, compared to the years prior to 2003.

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Pelvic Floor Symptoms May Lead To Exercise Avoidance in Menopausal Women

MedicalResearch.com Interview with:

Dr. Eija K. Laakkonen PhD Assistant professor Gerontology Research Center Faculty of Sport and Health Sciences University of Jyväskylä

Dr. Laakkonen

Dr. Eija K. Laakkonen PhD
Assistant professor
Gerontology Research Center
Faculty of Sport and Health Sciences
University of Jyväskylä

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

Response: Physical activity improves health and may delay the onset of chronic diseases. For women in particular, the rate of some chronic diseases accelerates at middle age around the time of menopause; therefore it is important to identify the determinants of health-enhancing physical activity during midlife in this population.

The main aim of this study was to characterize the level of physical activity and to examine the association between different female reproductive factors and objectively-measured physical activity in middle-aged women. The reproductive factors included cumulative reproductive history index, and perceived menopausal and pelvic floor dysfunction symptoms.

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Genetic Defect in DNA Repair Enzyme Linked to Prostate Cancer

MedicalResearch.com Interview with:
G. Andrés Cisneros, Ph.D.

Associate Professor
Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas

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

Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes.

Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function.

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Brain–Computer Interface Allows Communication With Locked-In Patients

MedicalResearch.com Interview with:

Dr. Ujwal Chaudhary, PhD Institute of Medical Psychology and Behavioral Neurobiology University of Tübingen Tübingen, Germany

Dr. Ujwal Chaudhary

Dr. Ujwal Chaudhary, PhD
Institute of Medical Psychology and Behavioral Neurobiology
University of Tübingen
Tübingen, Germany

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

Response: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder which causes an Individual to be in Locked-in state (LIS), i.e. the patients have control of their vertical eye movement and blinking, and ultimately in Completely Locked-in state (CLIS), i.e, no control over their eye muscle. There are several assistive and augmentative (AAC) technology along with EEG based BCI which can be used be by the patients in LIS for communication but once they are in CLIS they do not have any means of communication.  Hence, there was a need to find an alternative learning paradigm and probably another neuroimaging technique to design a more effective BCI to help ALS patient in CLIS with communication.

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Executive Brain Function Predictive of Success on the Soccer Pitch

MedicalResearch.com Interview with:
soccer; creative commons imageTorbjörn Vestberg

Licensed Psychologist & Researcher
Department of Clinical Neuroscience, Karolinska Institutet
Stockholm, Sweden

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

Response: The aim of our research is to study the importance of executive functions for successful behaviour. In our first study published in 2012 (Executive Functions Predict the Success of Top-Soccer Players) we showed that the level of elite soccer players’ higher executive functions was in general 2 standard deviations above the normal population. It was the same for both men and women.

Moreover, we also found a strong correlation between the capacities of higher executive functions and the number of goals and assists the player made after two and a half year.

In our new study we were interested in how the situation is at a younger age, from twelve to nineteen years of age. Because of the maturation of the brain, higher executive functions do not reach their full capacity before nineteen years of age.

On basis of this, our question was whether there were other parts of the executive functions that correlated with success in soccer. In this new study, we focused on core executive functions like the working memory, as it reaches its full capacity in the early teens. We found that there was a moderate correlation with the accuracy of the working memory and the number of goals the junior elite players made during a period of two years. When we made a composite measurement of both the demanding working memory and the test for the capacity of the higher executive functions, we found a strong correlation between these results and the number of goals that the players made during the two years of time. When we measured IQ and physical features, like length, we found out that those did not influence the results.

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Cost Effectiveness of Lung Cancer Screening Requires Careful Patient Selection

MedicalResearch.com Interview with:
Kevin ten Haaf MSc

Scientific researcher, Public Health
Erasmus Medical Center
Rotterdam

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

Response: Lung cancer screening is currently recommended in the United States, for persons aged 55 through 80 who smoked at least 30 pack-years (the average number of cigarettes smoked per day multiplied by the number of years the person has smoked) and who currently smoke or have quit within the last 15 years. Other countries, such as Canada, are investigating the feasibility of implementing lung cancer screening policies.

However, the cost-effectiveness of lung cancer screening in a population-based setting is uncertain. Concerns have been raised on the feasibility of implementing lung cancer screening policies, especially with regards to the potential costs. In this study, the benefits, harms and costs of implementing lung cancer screening in the province of Ontario, Canada were assessed.

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Does Maternal BMI Affect Offspring’s Obesity Risk?

MedicalResearch.com Interview with:

Dr Rebecca Richmond PhD

Dr Rebecca Richmond

Dr Rebecca Richmond PhD
Senior Research Associate in the CRUK Integrative Cancer Epidemiology Programme
MRC Integrative Epidemiology Unit
School of Social and Community Medicine
University of Bristol

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

Response: We have been involved in earlier work which applied the same methods used here (using genetic variants to provide causal evidence) and showed that higher maternal pregnancy body mass index (BMI) causes greater infant birth weight. The paper here aimed to build on that earlier research and asked whether maternal BMI in pregnancy has a lasting effect, so that offspring of women who were more overweight in pregnancy are themselves likely to be fatter in childhood and adolescence. Our aim was to address this because an effect of an exposure in pregnancy on later life outcomes in the offspring could have detrimental health consequences for themselves and future generations. However, we did not find strong evidence for this in the context of the impact of maternal BMI in pregnancy on offspring fatness.

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Transcranial Stimulation Reduced Bulimia Symptoms

MedicalResearch.com Interview with:

Dr Maria Kekic PhD

Dr. Maria Kekic

Dr Maria Kekic PhD
Research Worker | The TIARA study:
Transcranial magnetic stimulation and imaging in anorexia nervosa
Section of Eating Disorders | Department of Psychological Medicine
Institute of Psychiatry, Psychology & Neuroscience | King’s College London

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

Response: Bulimia nervosa is an eating disorder characterised by repeated episodes of binge-eating and inappropriate compensatory behaviours. It is associated with multiple medical complications and with an increased risk of mortality. Although existing treatments for bulimia are effective for many patients, a sizeable proportion remain symptomatic following therapy and some do not respond at all.

Evidence shows that bulimia is underpinned by functional alterations in certain brain pathways, including those that underlie self-control processes. Neuroscience-based techniques with the ability to normalise these pathways may therefore hold promise as treatments for the disorder.

One such technique is called transcranial direct current stimulation (tDCS) – a form of non-invasive brain stimulation that delivers weak electrical currents to the brain through two electrodes placed on the head. It is safe and painless, and the most common side effect is a slight itching or tingling on the scalp.

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In-Bed Cycling Feasible for ICU Patients on Ventilation

MedicalResearch.com Interview with:

Michelle Kho, PT, PhD</strong> Canada Research Chair in Critical Care Rehabilitation and Knowledge Translation Assistant Professor School of Rehabilitation Science McMaster University

Dr. Michelle Kho

Michelle Kho, PT, PhD
Canada Research Chair in Critical Care Rehabilitation and Knowledge Translation
Assistant Professor
School of Rehabilitation Science
McMaster University

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

Response: Patients who survive the ICU are at risk for muscle weakness and can experience physical functional disability lasting 5 to 8 years after the ICU. From a study conducted in Belgium, patients who were randomized to receive cycling after being in ICU for 2 weeks walked farther at ICU discharge than those who did not. Other research supported physiotherapy starting within days of starting mechanical ventilation to improve functional outcomes. Our CYCLE research program combines these 2 concepts – Can we start cycling very early in a patient’s ICU stay, and will this improve functional outcomes post-ICU?

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Genetics Magnifies Health Effects of Discrimination

MedicalResearch.com Interview with:

Connie J. Mulligan, PhD Professor, Department of Anthropology University of Florida Gainesville, FL

Dr. Connie J. Mulligan

Connie J. Mulligan, PhD
Professor, Department of Anthropology
University of Florida
Gainesville, FL

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

Response: Lance Gravlee (UF Dept of Anthropology, UF Genetics Institute) started this research over 10 years ago. As a cultural anthropologist, Lance uses ethnographic (open-ended questions) interviews and discovered that over half of the participants in our study talked about experiences of discrimination that happened to people close to them.

As a geneticist (UF Dept of Anthropology, UF Genetics Institute), I came into the project because I was interested in seeing how genetics and sociocultural stressors, like discrimination, interact. In our project, we look at blood pressure because hypertension is a disease that shows racial disparities and also because it is a complex disease that is caused by both genetic and environmental factors (like discrimination).

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Predictors of Chemosensitivity in Triple Negative Breast Cancer

MedicalResearch.com Interview with:

Christos Hatzis, PhD Assistant Professor of Medicine Director of Bioinformatics, Breast Medical Oncology Yale Comprehensive Cancer Center Yale School of Medicine New Haven, CT

Dr. Christos Hatzis,

Christos Hatzis, PhD
Assistant Professor of Medicine
Director of Bioinformatics, Breast Medical Oncology
Yale Comprehensive Cancer Center
Yale School of Medicine
New Haven, CT

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

Response: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients.

Identifying chemosensitive triple negative breast cancers could significantly impact
the survival of patients with these difficult to treat cancers until novel targeted
therapies become available. We hypothesized that genomic somatic aberrations may
provide important molecular clues about chemosensitivity in TNBC. Our study used
a carefully selected cohort of 29 uniformly treated TNBC patients who either achieved
pathologic complete response (pCR) or had extensive residual disease after neoadjuvant
anthracycline/taxane chemotherapy.

MedicalResearch.com: What are the main findings?

Response: We sequenced the coding genomic DNA of TNBC tumors and compared the somatic mutations found in the two groups at the two extremes of the chemosensitivity spectrum.

Our analysis revealed that, although mutations in single genes were not individually predictive, TNBC tumors bearing mutations in genes involved in the androgen receptor
(AR) and FOXA1 pathways were much more sensitive to chemotherapy.
We also found that mutations that lowered the levels of functional BRCA1 or BRCA2 RNA
were associated with significantly better survival outcomes; we derived a BRCA
deficiency signature to define this new, highly chemosensitive subtype of TNBC.
BRCA-deficient TNBC tumors have a higher rate of clonal mutation burden, defined as
more clonal tumors with a higher number of mutations per clone, and are also associated
with a higher level of immune activation, which may explain their greater chemosensitivity.

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

Response: Mutations in the AR/FOXA1 pathway provide a novel marker for identifying chemosensitive TNBC patients who may benefit from current standard-of-care chemotherapy regimens.

The newly defined RNA-based BRCA-deficient subtype includes up to 50% of the
Triple negative breast cancer tumors that appear to be immune primed, and it would be of interest to investigate combinations of chemotherapy with immunotherapies, which could provide clinical benefit for these patients. Although our study showed concordant results in three different datasets, our key findings need to be further validated in a larger, prospectively designed study with archival samples.

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

Response: The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in Triple negative breast cancer and suggests that functional RNA-based BRCA deficiency needs to be further examined in TNBC. Our results suggest that the combination of immunotherapies with ACT chemotherapy or PARP inhibitors might be an effective strategy for treating BRCA-D tumors.

The strong connection of ACT chemosensitivity and immune activity with a new transcriptionally defined BRCA-D phenotype could help inform future therapeutic strategies for TNBC patients.

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

Citation:

Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic AnalysisTingting Jiang,Weiwei Shi,Vikram B. Wali,Lőrinc S. Pongor,Charles Li,Rosanna Lau,Balázs Győrffy,Richard P. Lifton,William F. Symmans,Lajos Pusztai,Christos Hatzis

PLOS Medicine Published: December 13, 2016http://dx.doi.org/10.1371/journal.pmed.1002193

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

More Medical Research Interviews on MedicalResearch.com

Mental and Physical Disorders Linked at Early Age

MedicalResearch.com Interview with:

Dr-Gunther-Meinlschmidt.jpg

Prof. Dr. Gunther Meinlschmidt, Psych
University of Basel, Department of Psychology, Division of Clinical Psychology and Epidemiology
Faculty of Medicine
Switzerland

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

Response: Physical diseases and mental disorders affect a person’s quality of life. Further, they present a huge challenge for the healthcare system. It has been reported that physical and mental disorders systematically co-occur already early in life. What we wanted to know is whether there are certain temporal patterns between mental disorders and physical diseases during childhood and adolescence. A better understanding of such patterns may help to reveal processes that could be relevant both to the origins of physical diseases and mental disorders and to their treatment.

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Some Prions Can Be Cleared By Infected Organism

MedicalResearch.com Interview with:
Romolo Nonno, DVM, PhD
Istituto Superiore di Sanità
Dipartimento di Sanità Pubblica Veterinaria e Sicurezza Alimentare
Roma Italy

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

Response: Previous studies have suggested that prion populations are composed of a variety of conformational variants subjected to Darwinian evolution driven by selective regimes. However, the exact molecular mechanisms that make prions able to self-replicate and mutate are still poorly understood.

A major technical advance in this field has been the discovery of techniques that allow to replicate prions in vitro, outside live organisms. One of these techniques, Protein Misfolding Cyclic Amplification (PMCA), allows to grow prion populations for a very high number of replications in a relatively short time period.

Furthermore it is conceivable that the in vitro environment offers less constraint to prion replication than live animals or cells, due to the absence of active clearance and cell division, which are key players of conformers selection in ex vivo models. These features make PMCA an attractive tool to investigate prion replication, mutation and evolution. By using PMCA, we investigated the in vitro evolution of prion populations derived from natural scrapie. Unexpectedly, we found that the cloud of conformational variants which compose a natural scrapie isolate also includes “defective” variants which, once isolated, are unable to self-sustain in vivo.

Importantly, we found that the defective prion mutant that we have isolated possesses unique biochemical properties in that its prion domain lacks the central region of prion protein, which is invariably present in known infectious mammalian prions.

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Low Carb Meals Reduce Insulin Resistance

MedicalResearch.com Interview with>
Katarina Borer, Ph.D. Professor
Po-Ju Lin,PhD
School of Kinesiology
The University of Michigan
Ann Arbor, MI

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

Response: This study was part of the doctoral dissertation of Po-Ju Lin, who is now a post-doctoral fellow at the University of Rochester. With this study, we wanted to answer three questions:

(1) Is daily carbohydrate load responsible for evening glucose intolerance and post-meal insulin resistance. (Evening glucose intolerance represents well-documented higher glucose and insulin responses in the evening than in the morning when the same quantity of glucose is eaten or infused intravenously) To answer this question we offered two daily meals containing about 800 Kcal and either 30% or 60% of carbohydrates.

(2) Will exercise before the meals improve glucose tolerance (glucose clearance from the blood and insulin response) after eating? (Exercise is a well-known means of increasing glucose uptake by the muscle and of increasing muscle sensitivity to insulin action for a number of hours after exercise). To answer this question we had the subjects exercise for two hours walking on a treadmill at 45% of their maximal aerobic effort one hour before each meal.

(3) Is the upper-intestinal hormone GIP involved in any effects associated with variation in dietary carbohydrate? (GIP or glucose-dependent insulinotropic peptide, stimulates insulin secretion in advance of absorbed glucose).

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Adherent-Invasive E. coli May Markedly Raise Risk of Crohn’s Disease

MedicalResearch.com Interview with:

Brian K. Coombes, PhD Professor & University Scholar Associate Chair, Graduate Education Department of Biochemistry & Biomedical Sciences Assistant Dean, Biochemistry Graduate Program Canada Research Chair in Infectious Disease Pathogenesis

Dr. Brian Coombes

Brian K. Coombes, PhD
Professor & University Scholar
Associate Chair, Graduate Education
Department of Biochemistry & Biomedical Sciences
Assistant Dean, Biochemistry Graduate Program
Canada Research Chair in Infectious Disease Pathogenesis

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

Response: North Americans have among the highest reported prevalence and incidence of inflammatory bowel disease (IBD) in the world. This is a lifelong disease that often strikes people in their early years, leading to decades of suffering, increased risk of colorectal cancer, and 50% increased risk of premature death. Compared to the general population, quality of life for those with Crohn’s disease is low across all dimensions of health. The need to understand the root origins of this disease and to use this information to invigorate a new pipeline of treatments and preventions has never been more pressing.

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Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women

MedicalResearch.com Interview with:

Kenneth K. Mugwanya MBChB, MS Department of Epidemiology andDepartment of Global Health University of Washington, Seattle, Washington, USA Division of Disease Control, School of Public Health Makerere University Kampala, Uganda

Dr. Kenneth K. Mugwanya

Kenneth K. Mugwanya MBChB, MS
Department of Epidemiology andDepartment of Global Health
University of Washington, Seattle, Washington, USA
Division of Disease Control, School of Public Health
Makerere University
Kampala, Uganda

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

Response: Women living in regions with high HIV prevalence are at high risk of HIV acquisition in pregnancy and postpartum because they infrequently use condoms, do not know their partner’s HIV status, and have biologic changes or changes in their partner’s sexual partnerships that increase susceptibility. Moreover, acute HIV infection during pregnancy or breastfeeding period is associated with high rates of mother-to child HIV transmission because of high circulating level of HIV virus in blood. Oral antiretroviral pre-exposure prophylaxis (PrEP) is a powerful HIV prevention strategy recommended by both the World Health organization and US Centers for Diseases Control and Prevention. PrEP is an attractive prevention strategy for women as it can be used discreetly and independent of sexual partners. However, there is limited research about the safety of PrEP in HIV-uninfected pregnant or breastfeeding mothers and their infants.

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Is Muscle Memory a Myth?

MedicalResearch.com Interview with:

Maléne Lindholm, PhD Karolinska Institutet Dept. of Physiology & Pharmacology Stockholm Sweden

Dr. Maléne Lindholm

Maléne Lindholm, PhD
Karolinska Institutet
Dept. of Physiology & Pharmacology
Stockholm Sweden

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

Response: It is well known that exercise training provides marked health benefits and can prevent and treat a broad set of diseases. Therefore, a deeper understanding and characterization of the molecular processes behind training adaptation is essential for human health.

This study aimed at exploring the effects of endurance training on the human skeletal muscle transcriptome (activity of all genes) and investigate the possible presence of a muscle memory of training. To do this, the healthy volunteers in this study first trained only one leg, 4 times per week for 3 months. After 9 months of detraining, the subjects then came back and trained both legs in the same way as during the first training period, thus one leg was then previously well-trained and one previously untrained. This meant that each individual was their own control, as both legs have the same genome, experience the same stress, diet etc. Only the training status differed.

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Chronic Kidney Disease in Primary Care: Outcomes after Five Years in a Prospective Cohort Study

MedicalResearch.com Interview with:
Dr. Adam Shardlow

Derby Teaching Hospitals NHS Foundation Trust
UK

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

Response: Chronic Kidney Disease (CKD) is common in the general population, and many people are managed in primary care rather than by specialist nephrologists. This study was designed to investigate 5 year outcomes in people with mild to moderate CKD (CKD stage 3).

The main findings were that the majority of participants were stable, and progression to end stage renal disease was a rarity. Interestingly, and contrary to common thinking about CKD, we found that a significant minority no longer had evidence of CKD stage 3 at 5 years, which we have termed ‘CKD remission’.

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Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions May Differ

MedicalResearch.com Interview with:

Dr Su Golder PhD Research Fellow Department of Health Sciences University of York

Dr. Su Golder

Dr Su Golder PhD
Research Fellow
Department of Health Sciences
University of York

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

Response: Serious concerns have emerged regarding publication bias or selective omission of outcomes data, whereby negative results are less likely to be published than positive results. There remains considerable uncertainty about the extent of unpublished data on adverse events beyond that reported in the published literature. We aimed to estimate the potential impact of additional data sources and the extent of unpublished information when conducting syntheses of adverse events.

We found that less published papers contain adverse events information. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies.

We also found even when adverse events are reported in the published and unpublished versions of the same study that the numbers of adverse events do not always match The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%.
Lastly we found that inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in three-quarters of pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases.

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Cause and Preventative Treatment of Most Preterm Births Remains Unknown

MedicalResearch.com Interview with:

Dr. Joseph Leigh Simpson

Dr. Joseph Leigh Simpson

Joseph Leigh Simpson, MD FACOG, FACMG
President at International Federation of Fertility Societies
March of Dimes Foundation
White Plains, NY

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

Response: Preterm birth (PTB) is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. A total of 1.1 million infants die each year. Preterm births and their complications are the leading cause of deaths in children under age 5.

The biological basis of preterm birth remains poorly understood, and for that reason, preventive interventions are often empiric and have only limited benefit. Large differences exist in preterm birth rates across high income countries: 5.5 percent in Sweden and at present 9.6 percent in the U.S. The International Federation of Gynecologists and Obstetricians (FIGO)/March of Dimes Working Group on Preterm Birth Prevention hypothesized that identifying the risk factors underlying these wide variations could lead to interventions that reduce preterm birth in countries having high rates.

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Brain Scans Can Predict Specific Spontaneous Emotions

MedicalResearch.com Interview with:

Kevin S. LaBar, Ph.D. Professor and Head, Cognition & Cognitive Neuroscience Program Co-Director of Undergraduate Studies in Neuroscience Center for Cognitive Neuroscience Duke University Durham, NC

Dr. Kevin LaBar

Kevin S. LaBar, Ph.D.
Professor and Head, Cognition & Cognitive Neuroscience Program
Co-Director of Undergraduate Studies in Neuroscience
Center for Cognitive Neuroscience
Duke University
Durham, NC

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

Response: Emotion research is limited by a lack of objective markers of emotional states. Most human research relies on self-report, but individuals may not have good insight into their own emotions. We have developed a new way to identify emotional states using brain imaging and machine learning tools. First, we induced emotional states using film and music clips while individuals were in an MRI scanner. We trained a computer algorithm to identify the brain areas that distinguished 7 emotions from each other (fear, anger, surprise, sadness, amusement, contentment, and a neutral state). This procedure created a brain map for each of the 7 emotions. Then, a new group of participants self-reported their emotional state every 30 seconds in an MRI scanner while no stimuli were presented. We could predict which emotion was spontaneously reported by the subjects by comparing their brain scans to each of the 7 emotion maps. Finally, in a large group of 499 subjects, we found that the presence of the fear map during rest predicted state and trait anxiety while the presence of the sadness map predicted state and trait depression.

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Genotyping and 3D Imaging Help Identify Genes That Influence Facial Appearance

MedicalResearch.com Interview with:

Seth M. Weinberg, PhD

Dr. Seth Weinberg

Seth M. Weinberg, PhD
Assistant Professor, Department of Oral Biology
Assistant Professor, Department of Anthropology
Director, CCDG Imaging and Morphometrics Lab

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

Response: Scientists have long recognized that aspects of facial appearance have a genetic basis. This is most obvious when we look at the faces of people in the same family.  It is also well known that mutations in certain genes can result in syndromes where the face is affected.  However, very little is known about how specific genes influence the size and shape of normal human facial features.  To date, only a handful of studies have looked at this question, and while these studies have reported several interesting results, only a small number of genes have so far been linked to normal variation in facial features.  The primary goal of our study was to test for evidence of association between detailed facial measures derived from 3D images and common genetic variants spread across the entire genome.  We also attempted to independently replicate some of the findings from previous studies.

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Lung Cancers Detected On Screening CT Scans Have Better Survival

MedicalResearch.com Interview with:

Matthew B. Schabath PhD Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida

Dr. Matthew Schabath

Matthew B. Schabath PhD
Department of Cancer Epidemiology
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida

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

Response: Our study is a post-hoc analysis of data from a large randomized clinical trial (RCT) called the National Lung Screening Trial (NLST). The NLST found that lung cancer screening with low-dose helical computed tomography (LDCT) significantly reduced lung cancer deaths by 20 percent compared to screening with standard chest radiography (i.e., X-Ray).

In our publication, we performed a very detailed analysis comparing outcomes of lung cancer patients screened by LDCT according to their initial (i.e., baseline), 12 month, and 24 month screening results. We found that patients who had a negative baseline screening but tested positive for lung cancer at the 12- or 24-month screen had lower survival and higher mortality rates than patients who had a positive initial screen that was a non-cancerous abnormality but developed lung cancer in subsequent screens.

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Activating Scavenger System May Treat Blocked Blood Vessels Without Surgery

MedicalResearch.com Interview with:

MedicalResearch.com Interview with: Qing Kenneth Wang PhD, MBA Huazhong University of Science and Technology Wuhan, P. R. China and Department of Molecular Cardiology The Cleveland Clinic Cleveland, Ohio

Dr. Qing Kenneth Wang

Qing Kenneth Wang PhD, MBA
Huazhong University of Science and Technology
Wuhan, P. R. China and
Department of Molecular Cardiology
The Cleveland Clinic
Cleveland, Ohio

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

Response: Coronary Artery Disease (CAD) and its complication myocardial infarction (MI or so called heart attacks) are the most common causes of deaths in the US and other parts of the world. Based on the American Heart Association statistics, 620,000 Americans have a new MI each year in the United States alone, 295 000 have a recurrent MI, and nearly 400,000 of them will die from it suddenly. Moreover, an estimated 150,000 silent first MI occur each year.

CAD and MI are caused by an occlusion or blockage of a coronary artery, which disrupts blood flow to the heart region, leading to damage or death of cardiac cells, impairment of cardiac function and sudden death. Current treatment of CAD and MI relies on reperfusion therapy with reopening of the occluded coronary artery with percutaneous coronary intervention (PCA) and coronary artery bypass surgery (CABG). However, 12% of patients are not candidates for PCA or CABG due to an unfavorable occlusive pattern, diffuse coronary atherosclerosis, small distant vessels and co-morbidities. An alternative revascularization strategy has to be developed to benefit these patients.

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Preventing Bacteria From Sticking Would Eliminate Need For Antibiotics

MedicalResearch.com Interview with:

Dr Peter Monk BSc PhD Faculty Director of International Affairs Reader in Immunology Department of Infection, Immunity and Cardiovascular Disease Sheffield University Medical School

Dr. Peter Monk

Dr Peter Monk BSc PhD
Faculty Director of International Affairs
Reader in Immunology
Department of Infection, Immunity and Cardiovascular Disease
Sheffield University Medical School

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

Response: The tetraspanin proteins are found on the surface of all mammalian cells. The cell surface is the place where cells ‘socialise’: they talk to each other to coordinate activities, stick to each other to form tissues and sometimes crawl across each other to get to where they need to go. Tetraspanins have an important job to do in the organisation of the cell surface, amongst other things enabling the formation of ‘sticky patches’ (tetraspanin-enriched microdomains or TEM) that cause cells to adhere together or provide traction to allow movement. Some bacteria have evolved ways of hijacking the TEM for their own ends, adhering to tightly to these structures so that the normal things that sweep bacteria away (such as blood, sweat and tears!) are no longer effective. At this point, infection begins.

We have found that the TEM can be partly disrupted, by adding small parts of tetraspanins (peptides) to cells. The peptides seem to work by weakening the tetraspanin glue that holds the TEM together and causing the other components that give the ‘stickiness’ to the TEM to become more spaced out. We use the analogy of Velcro(TM), where the fabric hooks and loops are held together in woven material; loosen the weave and the hooks and loops fall apart, no longer able to engage strongly with the loops in the opposing piece of fabric.

Using reconstructed human skin, we were able to show that the tetraspanin peptides were both safe and effective; they did not affect wound healing in burned skin, but they could lower the bacterial load in the wound by 50%. This would allow the immune system (including the fluid that ‘weeps’ from wounds) to deal with the remaining bacteria more easily. Unlike conventional antibiotics that tend to kill bacteria, our peptides simply cause them to get washed away, so not invoking the evolutionary selective mechanisms that lead to resistance.

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Risk of Background Changes on Breast MRI Reexamined

MedicalResearch.com Interview with:

Barbara Bennani-Baiti, MD, MS

Dr. Bennani-Baiti

Barbara Bennani-Baiti, MD, MS and

Pascal Andreas Baltzer MD

Dr. P. Baltzer

Pascal Andreas Baltzer MD
Departement of Biomedical Imaging and Nuclear Medicine
Medical University of Vienna
Vienna, Austria

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

Response: Breast MRI ist the most sensitive method for detecting breast cancer. It is currently routinely used in the screening of high-risk patients and as an additional imaging technique in case of inconclusive conventional imaging (mammography and ultrasound).

Besides its high sensitivity for detection of breast cancer, breast MRI further provides functional information about normal breast tissue perfusion. Background parenchymal enhancement (BPE) reflects the perfusion or vascularization of the breast and is generally higher in active breast tissue. High-risk patients harbor breast tissue that is at an elevated risk for breast cancer due to several factors (i.e. mutations such as BRCA1, high familial risk, previous radiation of the chest wall, etc.). After a connection between increased breast cancer odds and elevated BPE has been shown in high-risk patients, the community has since assumed that an elevated background enhancement at breast MRI equates an elevated risk for breast cancer for all women. We have shown that this not true for women that are not considered high-risk. In fact, the only risk factor for women undergoing breast MRI without additional risk factors is age.

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For Selected Patients, Telehealth Offers Better Control of Diabetes

MedicalResearch.com Interview with:
Brian McKinstry MD Professor of primary care e-health and General practitioner MacKenzie Medical Centre EdinburghBrian McKinstry MD
Professor of primary care e-health and General practitioner
MacKenzie Medical Centre
Edinburgh

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

Response: The prevalence of diabetes is rising as the population ages and becomes more obese. Clinical services are increasingly stretched, so much so that it will be difficult for doctors and nurses to continue to look after patients using the same service delivery they have used in the past. Increasingly patients are being asked to self-manage long-term illnesses, but particularly with type 2 diabetes they find this stressful. One solution is to encourage self-management but with monitoring at a distance through telehealth.

We performed a randomised controlled trial in family practices in four regions of the United Kingdom among 321 people with type 2 diabetes and glycated haemoglobin (HbA1c) ( a measure of control over the previous three months) >58 mmol/mol. The supported telemonitoring intervention involved self-measurement and transmission to a secure website of twice weekly morning and evening glucose for review by family practice clinicians. The control group received usual care, with at least annual review and more frequent reviews for people with poor glycaemic or blood pressure control in the context of incentives in family practice based on a sliding scale of financial rewards for achieving glycaemic and blood pressure control targets. HbA1c assessed at nine months was the primary outcome. Intention-to-treat analyses were performed.

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Human Brains, Because of Size, More Prone to Disconnection Syndromes

MedicalResearch.com Interview with:

Zoltan Toroczkai, PhD, Professor of Physics Concurrent Professor of Computer Science and Engineering Physics Department University of Notre Dame, Notre Dame, IN, 46556 --

Dr. Zoltan Toroczkai

Zoltan Toroczkai, PhD, Professor of Physics
Concurrent Professor of Computer Science and Engineering
Physics Department
University of Notre Dame, Notre Dame, IN, 46556

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

Response: The mammalian brain is arguably the most complex information processing network and with billions of neurons and trillions of connections it presents formidable challenges to deciphering its fundamental mechanisms for information processing. In the brain, information is encoded into the spatio-temporal firing patterns of groups of neurons (population coding), making the connectivity structure of the network crucial for brain function. Damages to this network have been associated with diseases such as Alzheimer’s, autism and schizophrenia, and thus understanding the cortical network would also help better understand certain diseases of the brain.

An experimentally and computationally more feasible approach is to study the anatomical (physical connectivity) network between the functional areas of the cortex, a mosaic of brain patches, each associated with a specific function (e.g., visual, auditory, somatosensory). Based on phylogenic considerations one expects the existence of common fundamental network architectural (and implicitly, processing) principles to be present in all mammalian brains. However, the mammalian brain spans over five orders of variation in size and thus it is not clear at all what are this common architectural features and how would we find them. The challenge here is to compare networks of the same nature (information processing type) but of different orders, with different nodal identities, and of very different spatial embedding (geometrical size) properties.

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Study Evaluates Effects of Polyunsaturated Fats on Development of Diabetes

MedicalResearch.com Interview with:

Dr. Fumiaki Imamura Ph.D. MRC Epidemiology Unit University of Cambridge

Dr. Fumiaki Imamura

Dr. Fumiaki Imamura Ph.D.
MRC Epidemiology Unit
University of Cambridge

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

Response: There was insufficient evidence for effects of polyunsaturated fatty acids (PUFA) intake or blood biomarkers on the development of type 2 diabetes. For instance, previous studies using PUFA biomarkers had a maximum of only 673 type 2 diabetes cases. In the EPIC-InterAct Study – a large European collaborative, prospective study where 12,132 diabetes cases were ascertained during its follow-up – we found diverse associations of blood levels of different types of PUFAs with incidence of type 2 diabetes.

Despite this diversity, clinically relevant results were observed for major polyunsaturated fatty acids. Higher blood levels of total omega-6 PUFAs and the major omega-6 PUFA (linolenic acid) were associated with a lower risk of developing type 2 diabetes. Likewise, levels of alpha linolenic acid, known as a plant-origin omega-3 PUFA, were associated with lower type 2 diabetes risk. Marine-origin omega-3 PUFAs, including docosahexaenoic acid (DHA), showed inconsistent associations with type 2 diabetes risk.

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