High Fiber Diet During Pregnancy May Reduce Risk of Childhood Asthma

Dr. Alison Thorburn Ph.D. School of Medical and Applied Sciences, Central Queensland University Rockhampton, Queensland 4702, AustraliaMedicalResearch.com Interview with:
Dr. Alison Thorburn Ph.D.
Department of Immunology
Monash University
Victoria, Australia

Medical Research: What is the background for this study?

Dr. Thorburn: Asthma is a highly prevalent disease in the Western World. The prevailing explanation for this has been the hygiene hypothesis, which proposes that a decline in family size and improved hygiene has decreased exposure to infectious agents and therefore resulted in dysregulated immune responses that lead to asthma. However, recently there has been more attention on the role of diet and the gut microbiota in explaining the prevalence of inflammatory diseases in Western World. Indeed, many studies implicate obesity, as well as a high fat, low fruit and vegetable diet with higher prevalence of asthma. On the other hand, a Mediterranean diet, which is high in fruit and vegetables, is associated with lower prevelance of asthma. Interestingly, the consumption of dietary fiber is reduced in severe asthmatics. These and other data suggest that the diet (particularly dietary fibre) and the gut microbiota may play an important role in the development of asthma.

Medical Research: What are the main findings?

Dr. Thorburn: The main findings of this study are that:

–        In mice: A high-fiber diet promotes a gut microbiota that produces high levels of anti-inflammatory short-chain fatty acids (SCFAs), particularly acetate. Acetate (alkaline form of vinegar) suppressed the development of allergic airways disease (AAD, a model for human asthma) in adult mice and the offspring of pregnant mice.

–        In humans: High dietary fiber intake during late pregnancy is associated with higher acetate levels in the serum and a decrease in the percentage of infants showing predictors for asthma development in later life.

–        The mechanism underlying these findings involves increasing T regulatory cell number and function through epigenetic mechanisms, which enhance immune regulation to prevent inflammation.

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Both Young and Old Lose Muscle Strength After Short Term Inactivity

MedicalResearch.com Interview with:
Andreas Vigelsø PhD, research assistant
University of Copenhagen
Faculty of Health Sciences
Center for Healthy Aging
Dept. of Biomedical Sciences
Copenhagen Denmark

Medical Research: What is the background for this study?

Response: According to the UN, the number of individuals more than 60 years old is expected to more than double, from 841 million worldwide today to more than 2 billion in 2050. Furthermore, the aging process is associated with a reduction in muscle mass, strength and fitness level. Collectively, this may contribute to frailty and may limit independent living. In addition, disease or injuries that can cause short-term immobilization are a further threat to independent living for older individuals. Despite its clinical importance for an increasing population of older individuals, few studies have examined older individuals after immobilization. Thus, our aim was to determine the effect of aerobic retraining as rehabilitation after short-term leg immobilization on leg strength, leg work capacity, and leg muscle mass in young and older men.

Medical Research: What are the main findings?

Response: Interestingly, our study reveals that inactivity affects the muscular strength in young and older men equally. Having had one leg immobilized for two weeks, young people lose up to a third of their muscular strength, while older people lose approx. one fourth. A young man who is immobilized for two weeks loses muscular strength in his leg equivalent to ageing by 40 or 50 years. Moreover, short-term leg immobilization had marked effects on leg strength, and work capacity and 6 weeks’ retraining was sufficient to increase, but not completely rehabilitate, muscle strength, and to rehabilitate aerobic work capacity and leg muscle mass. Continue reading

Surgery for GERD May Improve Reflux But Risks Complications

John Maret-Ouda  MD,  PhD candidateMedicalResearch.com Interview with:
John Maret-Ouda  MD,  PhD candidate
Upper Gastrointestinal Surgery
Department of Molecular medicine and Surgery
Karolinska Institutet
Stockholm, Sweden

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

Dr. Maret-Ouda : This review is part of the BMJ series “Uncertainties pages”, where clinically relevant, but debated, medical questions are highlighted and discussed. The present study is assessing treatment of severe gastro-oesophageal reflux disease, where the current treatment options are medical (proton-pump inhibitors) or surgical (laparoscopic antireflux surgery). The clinical decision-making is often left to the clinician and local guidelines. We evaluated the existing literature to compare the two treatment options regarding reflux control, complications, future risk of oesophageal adenocarcinoma, health related quality of life, and cost effectiveness.

The main findings were that surgery might provide slightly better reflux control and health related quality of life, but is associated with higher risks of complications compared to medication. A possible preventive effect regarding oesophageal adenocarcinoma remains uncertain. Regarding cost effectiveness, medication seems more cost effective in the short term, but surgery might be more cost effective in the longer term. Since medication provides good treatment of severe gastro-oesophageal reflux disease, but with lower risks of complications, this remains the first line treatment option.

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Sugar and Fat Absorption Increased In Obesity

Dr. Karine Clément M.D., Ph.D. Assistant Professor, Nutrition Department Hotel-Dieu hospital ParisMedicalResearch.com Interview with:
Dr. Karine Clément M.D., Ph.D.
Assistant Professor, Nutrition Department
Hotel-Dieu hospital Paris

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

Dr. Clément: Obesity, associated with insulin resistance, is a chronic inflammatory disease revealed by a moderate but long-term increase in the levels of inflammatory molecules in the blood.

Our groups and others have shown that several organs such as adipose tissues, liver, pancreas and muscles are also sites of inflammation with accumulation of immune cells such as macrophages and lymphocytes. This low-grade inflammatory state perturbs the tissue biology and contributes to the development and/or maintenance of insulin resistance and diabetes. In addition our teams and others showed that the intestinal functions are altered in obesity such as sugar and lipid absorption of and enteroendocrine nutrient signaling to the whole body.

Our teams showed modifications of immunity in the obese intestine, and particularly in the jejunum part where most of sugar and lipid absorption takes place. Obesity increases the absorptive surface of the intestine and the colonization of the epithelium by CD8αβ T lymphocytes not affecting tissue integrity, thus differing from IBD inflammation. The cytokines secreted by the CD8 T cells of obese, but not lean subjects, are able to inhibit insulin action in enterocytes. In these patients, the increase of intestinal CD8 T cell density correlates with sugar absorption capacity and with the level of obesity and associated complications such as liver disease (NASH – Non-Alcoholic SteatoHepatitis) and dyslipidemia.

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Women With PTSD At Higher Risk For Heart Disease

Jennifer A. Sumner, Ph.D.MedicalResearch.com Interview with:
Jennifer A. Sumner, Ph.D.
Columbia University Mailman School of Public Health
New York, NY 10032

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

Dr. Sumner: Cardiovascular disease, which includes conditions like heart attack and stroke, is the leading cause of death worldwide. Stress has long been thought to increase risk of cardiovascular disease, and posttraumatic stress disorder (PTSD) is the quintessential stress-related mental disorder. Some individuals who are exposed to traumatic events, such as unwanted sexual contact, the sudden unexpected death of a loved one, and physical assault, develop PTSD, which is characterized by symptoms of re-experiencing the trauma (e.g., nightmares), avoidance of trauma reminders (e.g., avoiding thinking about the trauma), changes in how one thinks and feels (e.g., feeling emotionally numb), and increased physiological arousal and reactivity (e.g., being easily startled). PTSD is twice as common in women as in men; approximately 1 in 10 women will develop PTSD in their lifetime. Research has begun to suggest that rates of cardiovascular disease are higher in people with PTSD. However, almost all research has been done in men.

My colleagues and I wanted to see whether PTSD was associated with the development of cardiovascular disease in a large sample of women from the general public. We looked at associations between PTSD symptoms and new onsets of heart attack and stroke among nearly 50,000 women in the Nurses’ Health Study II over 20 years, beginning in 1989. Women with the highest number of PTSD symptoms (those reporting 4+ symptoms on a 7-item screening questionnaire) had 60% higher rates of developing cardiovascular disease (both heart attack and stroke) compared to women who were not exposed to traumatic events. Unhealthy behaviors, including lack of exercise and obesity, and medical risk factors, including hypertension and hormone replacement use, accounted for almost 50% of the association between elevated PTSD symptoms and cardiovascular disease. We also found that trauma exposure alone (reporting no PTSD symptoms on the screening questionnaire) was associated with elevated cardiovascular disease risk compared to no trauma exposure.

Our study is the first to look at trauma exposure and PTSD symptoms and new cases of cardiovascular disease in a general population sample of women. These results add to a growing body of evidence suggesting that trauma and PTSD have profound effects on physical health as well as mental health.

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Active Surveillance Utilization For Prostate Cancer Remains Low

Hui Zhu, MD, ScD Section Chief, Urology Section Louis Stokes Cleveland Veterans Affairs Medical Center and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation Cleveland, Ohio MedicalResearch.com Interview with:
Hui Zhu, MD, ScD
Section Chief, Urology Section
Louis Stokes Cleveland Veterans Affairs Medical Center
and Staff, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation
Cleveland, Ohio

MedicalResearch: Tell me a little bit about the impetus for this study. What gap in knowledge were you trying to fill? 

Dr. Zhu: Prostate cancer is a very challenging disease to understand and manage. For the minority of men, prostate cancer is a lethal disease, and in fact, it is the second leading cause of cancer death in American men, behind only lung cancer. However, for the majority of men, prostate cancer poses little risk of death. In fact, about 1 man in 7 will be diagnosed with prostate cancer during his lifetime, but only 1 man in 38 will die from prostate cancer.

In an effort to avoid suffering and death from prostate cancer for those men with the lethal form, the early detection of prostate cancer (before the disease has reached a stage when it is no longer curable) through widespread prostate cancer screening was instituted in the late 1980s and early 1990s. As a result, prostate cancer diagnosis increased substantially, and most prostate cancers were detected at an early, treatable stage. Screening successfully reduced the risk of death from prostate cancer by 20%.

Unfortunately, our best available screening tests, i.e. prostate-specific antigen (PSA) testing and the digital rectal exam, do not differentiate well between lethal and nonlethal prostate cancer. Consequently, screening is associated with a high risk of overdiagnosis of nonlethal prostate cancer. As a result, about 800 men must be screened and about 30 men must be diagnosed and treated to avoid one death from the prostate cancer, according to recent results from the largest prostate cancer screening trial.

Since the natural history of newly diagnosed screen-detected prostate cancer is difficult to predict (i.e. lethal or nonlethal), most prostate cancers have been treated aggressively, leading to overtreatment of many nonlethal cancers. Aside from receiving unnecessary treatment, these men are exposed to the potential side effects and complications of treatment, including erectile dysfunction and urinary incontinence.

In response to the harms associated with screening and treatment, the US Preventative Services Task Force issued a statement in 2011 (formalized in 2012) recommending against prostate cancer screening in all men. Unfortunately, while minimizing the risks of overdiagnosis and overtreatment for men with nonlethal prostate cancer, this solution eliminates any of the potential benefits of screening for those men with the lethal form of the disease.

As urologists, our solution is different. Rather than throw the baby out with the bathwater, we prefer to preserve PSA screening and its benefits by addressing and hopefully minimizing its associated risks. To achieve this, our goal is to better distinguish between those men who have lethal vs. nonlethal prostate cancer, limiting treatment only to those men who have the lethal form of the disease at an early stage when it is still curable. The dilemma is that our currently available diagnostic tests are unable to accurately differentiate lethal from nonlethal prostate cancer with 100% certainty at the time of initial diagnosis.

The solution, or at least part of the solution, is active surveillance. In men who appear to have nonlethal (“low risk”) cancer at the time of diagnosis, it now appears to be safe to observe these cancers, at least initially. This is the concept behind active surveillance. Active surveillance entails carefully monitoring men with low-risk prostate cancer using serial testing and reserving the option of treatment for those men with prostate cancers that exhibit lethal characteristics. In this way, active surveillance preserves the benefits of screening while minimizing the harms of overdiagnosis and overtreatment.

Active surveillance was first introduced in the early 2000s, but its efficacy and safety have only been elucidated recently over the last 5 years. Given that active surveillance may be one solution to the screening dilemma, we wanted to evaluate contemporary active surveillance utilization, which is the impetus for our study. Based on the most recent data available to us, we chose the years 2010-2011, which coincide to the time immediately before and during the release of the US Preventative Services Task Force statement against PSA screening.

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Lymph Node Cancer Metastases Do Not Require Growth of New Blood Vessels

Timothy P. Padera, PhD Edwin L. Steele Laboratories Department of Radiation Oncology MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School Boston, Massachusetts 02114MedicalResearch.com Interview with:
Timothy P. Padera, PhD
Edwin L. Steele Laboratories
Department of Radiation Oncology
MGH Cancer Center, Massachusetts General Hospital and Harvard Medical School
Boston, Massachusetts 02114

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

Dr. Padera: Systemic therapy benefits cancer patients with lymph node metastases; however all phase III clinical trials to date of antiangiogenic therapy have failed in the adjuvant setting. We have previously reported the lack of efficacy of antiangiogenic therapies in pre-clinical models of spontaneous lymphatic metastasis, however there were no mechanistic data to explain these observations. Here, we developed a novel chronic lymph node window model to facilitate new discoveries in the mechanisms of growth and spread of lymph node metastases. Our new data provide pre-clinical evidence along with supporting clinical evidence that angiogenesis does not occur in the growth of metastatic lesions in the lymph node. These results reveal a mechanism of treatment resistance to antiangiogenic therapy in adjuvant setting, particularly those involving lymph node metastases.

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More Sunshine Linked to Better IVF Outcomes

Frank Vandekerckhove, MD, PhD Clinical Head, Centre for Reproductive Medicine University Hospital Ghent BelgiumMedicalResearch.com Interview with:
Frank Vandekerckhove, MD, PhD
Clinical Head, Centre for Reproductive Medicine
University Hospital Ghent

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

Dr. Vandekerckhove: Several retrospective studies have evaluated seasonal variations in the outcome of IVF treatment. Some also included weather conditions, mostly temperature and hours of daylight. The results were conflicting. We focused on individual variables provided as monthly results by our national meteorological institute. We shifted the results in IVF outcome to the weather results of one month earlier, as we supposed that the selection of good quality oocytes may start in the weeks before.

Between January 2007 and December 2013, the IVF outcome of all Belgian patients treated in our university center was compared to the quarter of the year and monthly mean values of temperature, rain fall, rainy days and sunshine hours during the month when gonadotropins were started or the month before.

11494 patients started an IVF cycle and were included. Firstly bivariate correlation was performed by linear modelling between monthly weather conditions and IVF results. Secondly the same IVF outcome variables were plotted against the weather results stratified per quartile for each individual meteorological variable.

There was no relationship between IVF outcome and the quarter of the year.

When looking for a linear correlation between IVF results and the mean monthly values for the weather, the results were inconsistent.

However, when the same analysis was repeated with the weather results of 1 month earlier, there was a clear trend towards better IVF outcome with higher temperature, less rain and more sunshine hours. The live birth rate per cycle was significantly different (p 0.019) between different groups (Q=quartile) of mean number of sunshine hours (Q1=60.75, Q2=136.00, Q3=174.50).

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Flu Vaccine Less Effective This Year Because Flu Virus Acquired A Mutation

Scott E. Hensley, Ph.D. Assistant Professor Wistar Institute Philadelphia, PA 1910MedicalResearch.com Interview with:
Scott E. Hensley, Ph.D.
Assistant Professor
Wistar Institute
Philadelphia, PA 1910


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

Response: Previous studies documented that the the 2014-2015 H3N2 flu vaccine strain was antigenically distinct compared to most recent H3N2 flu strains.  Recent H3N2 strains possess several mutation and it was previously unknown which of these mutations contributed to the 2014-2015 vaccine mismatch.  We used a reverse-genetic engineering approach to identify specific viral mutations that contributed to the 2014-2015 vaccine mismatch.

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Acidification May Be Counterproductive For Some Patients With Urinary Tract Infections

MedicalResearch.com Interview with:
Jeffrey P. Henderson, M.D., Ph.D.
Assistant Professor of Medicine and Molecular Microbiology
Center for Women’s Infectious Diseases Research
Division of Infectious Diseases

and Robin Shields-Cutler, Ph.D
Ph.D. Student, Molecular Microbiology and Microbial Pathogenesis
Washington University School of Medicine
St. Louis, Missouri

Medical Research: What is the background for this study?

Response: Increasing antibiotic resistance, together with an appreciation that many patients are particularly susceptible to recurrent Urinary Tract Infections UTIs following antibiotic therapy, motivated interest in the events that occur during early stages of UTI pathogenesis.

Abundant evidence suggests that uropathogenic E.coli must obtain iron from human hosts in order to cause a clinical infection. Early in infection, human cells secrete a protein called siderocalin that is known to limit bacterial growth by sequestering iron. This protein is detectable in the urine of Urinary Tract Infections patients.

Medical Research: What are the main findings?

Response: We obtained urine from a diverse panel of healthy volunteers, inoculated them individually with a uropathogenic E.coli strain, and monitored growth in the presence and absence of a fixed amount of siderocalin. Siderocalin exhibited a remarkably wide range of activity between individuals.

We traced this variation back to differences in urinary pH and to phenolic urinary metabolites. We could significantly facilitate siderocalin’s antibacterial activity in urine by alkalinizing it above 6.5 and adding phenolic metabolites. The metabolites that potentiate siderocalin’s antibacterial effect have been linked to dietary sources such as coffee, tea, and berries. Some of these compounds may further derive from the actions of gut microbes on dietary phenols. The functional basis for these compounds’ properties seems to arise from siderocalin’s ability to use them as molecular grips that chelate iron ions in a form that is difficult for bacteria to access.

From the pathogen perspective, we found that enterobactin, a molecule secreted by E.coli, acts as a microbial countermeasure to urinary siderocalin. Adding a drug-like inhibitor to urine that blocks enterobactin biosynthesis greatly increased siderocalin’s antibacterial effect.

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