Even Low Dose Physical Activity Helpful In Reducing Mortality

MedicalResearch.com Interview with:
Dr David Hupin

CHU Saint-Etienne, Hôpital Nord
Service de Physiologie Clinique et de l’Exercice, Centre VISAS
Cedex 2, France

Medical Research: What is the background for this study?

Dr. Hupin: Today, over 95% of the world’s population has health problems, according to the Global Burden of Disease Study published recently in The Lancet. The proportion of healthy years lost due to disease rapidly increased with age. There is no medical treatment that can influence as many diseases in a positive manner as can physical activity. It is well established that regular physical activity is an efficient strategy for successful aging. The 2008 Physical Activity guidelines for Americans recommend a minimum of 150 min of moderate-intensity (>3 MET) or 75 min of vigorous-intensity (≥6 MET) physical activity per week or an equivalent combination of moderate and vigorous physical activity (MVPA). A Metabolic Equivalent or MET is a unit useful for describing the energy expenditure of a specific physical activity. However, less than 50% of older adults are able to achieve the current recommendations of physical activity. Thus, the prescription of physical activity for older adults needs to be clarified, i.e., what “dose” of physical activity is required.

Medical Research: What is the design of your study?

Dr. Hupin: Within the dynamic Department of Clinical and Exercise Physiology of University Hospital of St-Etienne, we conducted a systematic review and meta-analysis. Out of at total of 835 relevant studies, nine were suitable for analysis. These involved a total of 122, 417 participants, monitored for an average of around 10 years, during which time 18,122 died.

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Mindfulness-Based Stress Therapy May Reduce PTSD Symptoms in Veterans

Melissa A. Polusny, PhD, LP Staff Psychologist/Clinician Investigator Core Investigator, Center for Chronic Disease Outcomes Research Associate Professor, University of Minnesota Medical School Minneapolis VA Health Care System (B68-2) One Veterans Drive Minneapolis, MN 5541MedicalResearch.com Interview with:
Melissa A. Polusny, PhD, LP
Staff Psychologist/Clinician Investigator
Core Investigator, Center for Chronic Disease Outcomes Research
Associate Professor, University of Minnesota Medical School
Minneapolis VA Health Care System
One Veterans Drive Minneapolis, MN 5541

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

Dr. Polusny: VA has invested heavily in the dissemination of prolonged exposure therapy and cognitive processing therapy as first-line treatments for PTSD; however, 30% to 50% of Veterans do not show clinically significant improvements and dropout rates are high. Evidence suggests that mindfulness-based stress reduction – an intervention that teaches individuals to attend to the present moment in a non-judgmental, accepting manner – can reduce symptoms of anxiety and depression. This randomized clinical trial compared mindfulness-based stress reduction with present-centered group therapy – sessions focused on current life problems. We randomly assigned 116 Veterans with PTSD to receive nine sessions of mindfulness-based stress reduction therapy (n=58) or nine sessions of present-centered group therapy (n=58). Outcomes were assessed before, during and after treatment, and at two-month follow-up. Exclusion criteria included: substance dependence (except nicotine), psychotic disorder, suicidal or homicidal ideation, and/or cognitive impairment or medical illness that could interfere with treatment. The primary outcome was a change in self-reported PTSD symptom severity over time. Secondary outcomes included interview-rated PTSD severity scores, self-reported depression symptoms, quality of life, and mindfulness skills.

Mindfulness-based stress reduction therapy – compared with present-centered group therapy – resulted in a greater decrease in self-reported PTSD symptom severity. Veterans in the mindfulness-based stress reduction group were more likely to show clinically significant improvement in self-reported PTSD symptom severity (49% vs. 28%) at two-month follow-up, but they were no more likely to have loss of PTSD diagnosis (53% vs. 47%). Veterans participating in mindfulness-based stress reduction therapy reported greater improvement in quality of life and depressive symptoms than those in present-centered group therapy; however improvement in depressive symptoms scores did not reach the level of significance. Improvements in quality of life made during treatment were maintained at 2-month follow-up for Veterans in the mindfulness-based stress reduction group, but reports of quality of life returned to baseline levels for those in present-centered group therapy. The dropout rate observed for mindfulness-based stress reduction therapy (22%) in this study was lower than dropout rates reported in previous studies for PE (28.1% to 44%) and CPT (26.8% to 35%).

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Hospitals Vary in Rates of Missed Acute Myocardial Infarction Diagnosis

MedicalResearch.com Interview with:
Philip G. Cotterill PhD
Centers for Medicare & Medicaid Services
Baltimore, MD

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

Dr. Cotterill: Chest pain is one of those elusive complaints where patients can seem initially low-risk based on symptoms or risk factors, and subsequently have an acute myocardial infarction (AMI) or die in a short period of time. Using combinations of history and physical examination findings to discriminate patients with serious causes of chest pain is often not possible. In our study, we demonstrated wide variation in the decision to hospitalize Medicare beneficiaries with chest pain – nearly two fold between the lowest (38%) and highest (81%) quintile of hospitals – and that patients treated in hospitals with higher admission rates for chest pain are less likely to have an acute myocardial infarction within 30-days of the index event and less likely to die.

While the findings were statistically significant – differences in outcomes were small: 4 fewer AMIs and 3 fewer deaths per 1,000 patients comparing the highest and lowest admission quintiles. Stated differently, these numbers suggest that if low admitting hospitals were to behave more like high admitting hospitals, 250 patients would need to be admitted to prevent one AMI and 333 cases to prevent one death.

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Primary Care Study: Screening Women For Partner Violence Did Not Improve Health

Joanne Klevens, MD, PhD Division of Violence Prevention US Centers for Disease Control and Prevention Atlanta, GeorgiaMedicalResearch.com Interview with:
Joanne Klevens, MD, PhD
Division of Violence Prevention
US Centers for Disease Control and Prevention
Atlanta, Georgia

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

Dr. Klevens: The United States Preventive Services Task Force recommends women of reproductive age be screened for partner violence but others, such as the World Health Organization and the Cochrane Collaborative conclude there is insufficient evidence for this recommendation. Our randomized clinical trial allocated 2700 women seeking care in outpatient clinics to 1 of 3 study groups: computerized partner violence screening and provision of local resource list, universal provision of partner violence resource list without screening, or a no-screen/no resource list control group.  No differences were found in women’s quality of life, days lost from work or housework, use of health care and partner violence services, or the recurrence of partner violence after 1 year. In this three-year follow-up, no differences were found in the average number of hospitalizations, emergency room visits or ambulatory care visits.

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Young Fathers May Die Early

MedicalResearch.com Interview with:
Elina Einiö PhD

Postdoctoral Researcher
Population Research Unit, Department of Social Research
University of Helsinki Finland

Medical Research: What is the background for this study?

Response: Some previous studies have shown that young fatherhood is associated
with poorer health and higher later-life mortality. It was unclear
whether the association is credible, in the sense that mortality and
young fatherhood just appear to be associated because both are
determined by family related social and genetic characteristics.

Medical Research: What are the main findings?

Response: Men who had their first child before age 22 or at ages 22-24 had a
higher risk of dying early in middle age than their brothers who had
their first child at the average age of 25-26 years.

These findings suggest a causal effect of young fatherhood on midlife
mortality.

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No Evidence of Anti-Inflammatory Mediators From Fish Oil Ingestion

Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of PennsylvaniaMedicalResearch.com Interview with:
Carsten C. Skarke MD
Research Assistant Professor of Medicine
McNeil Fellow in Translational Medicine
Institute for Translational Medicine and Therapeutics
Perelman School of Medicine
University of Pennsylvania

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

Dr. Skarke: A growing body of publications suggests anti-inflammatory actions of fish oils. These health benefits are proposed to emerge from lipids called specialized pro-resolving mediators, (SPMs), which can be formed from omega-3 polyunsaturated fatty acids found in fish. A limitation to date, though, in this field is that there is little evidence of their formation in humans. And the cases where presence of these lipids is reported in humans, less rigorous analytical approaches, such as enzyme immunoassay (EIA), radioimmunoassay (RIA) or mass spectrometry without internal authentic standards, have been used. Thus, the specific aim for our study was to use state-of-the-art mass spectrometry to identify and quantify these specialized pro-resolving mediators.

Several aspects of our study design set us apart from what was done in previous studies.

  • First, we biased our ability to detect SPMs formed in healthy volunteers by giving fish oil in high doses which had been previously shown to influence blood pressure and platelet aggregation under placebo-controlled conditions.
  • Second, we also looked at lower doses of fish oil, those more commonly consumed by the general public, for the formation of SPMs during an acute inflammatory response and its resolution.
  • Third, we relied in our measurements of SPMs on authentic internal standards. These deuterated lipids, d4-resolvin E1 for example, facilitate distinct identification of the naturally formed lipid.
  • And fourth, we achieved very low limit of detection levels, below 10 pg/ml for resolvin E1, for example.

The surprising finding of our studies is that we failed to detect a consistent signal of SPM formation in urine or plasma of healthy volunteers who had taken fish oil. Even more surprising was that we found no alteration in the formation of SPMs during the resolution of inflammation. These results let us question the relevance of endogenous specialized pro-resolving mediators to the putative anti-inflammatory effects of fish oils in humans.

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Patient-Derived Stem Cells May Be Able To Reverse Hemophilia A

MedicalResearch.com Interview with:
Dong-Wook Kim
Center for Genome Engineering, Institute for Basic Science
Yonsei University College of Medicine
Seoul, Korea

Medical Research: What is the background for this study?

Response: Hemophilia A is an X-linked genetic disorder caused by mutations in the F8 gene, which encodes the blood coagulation factor VIII. Almost half of all severe hemophilia A cases result from two gross (140-kbp or 600-kbp) chromosomal inversions. We derived induced pluripotent stem cells (iPSCs) from patients with these inversion genotypes and used CRISPR-Cas9 nucleases to revert these chromosomal segments back to the WT situation.

Medical Research: What are the main findings?

Response: We isolated inversion-corrected iPSCs with frequencies of up to 6.7% without detectable off-target mutations based on whole-genome sequencing or targeted deep sequencing. Endothelial cells differentiated from corrected iPSCs expressed the F8 gene and functionally rescued factor VIII deficiency in an otherwise lethal mouse model of hemophilia.

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

Response: Our results provide a proof of principle for functional correction of large chromosomal inversions in Hemophilia patient-derived induced pluripotent stem cells and suggest potential therapeutic applications in the future.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: We need to prove the safety of patient-derived iPSCs before we move towards clinics.

The safety of iPSCs means to prevent teratoma formation when we do clinical trials.

For that purpose, we need to develop good differentiation protocols into EC cells and to purify the cells as well. In addition, we need much more animal study.

Citation:

Functional Correction of Large Factor VIII Gene Chromosomal Inversions in Hemophilia A Patient-Derived iPSCs Using CRISPR-Cas9

Chul-Yong Park Duk Hyoung Kim Jeong Sang Son Jin Jea Sung Jaehun Lee Sangsu Bae Jong-Hoon Kim Dong-Wook Kim Jin-Soo Kim

Cell Stem Cell Available online 23 July 2015

doi:10.1016/j.stem.2015.07.001

Dong-Wook Kim (2015). Patient-Derived Stem Cells May Be Able To Reverse Hemophilia

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Blood Pressure Dippers May React Differently to Morning Blood Pressure Surge

MedicalResearch.com Interview with:
Prof. Sante D. Pierdomenico
Associate Professor of Internal Medicine
University “Gabriele d’Annunzio”
Chieti-Pescara – Italy

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

Dr. Pierdomenico: Though a peak incidence of cardiovascular events in the morning has
been observed, the independent prognostic value of morning surge (MS)
of blood pressure (BP) is not yet clear. We investigated the
association between morning surge of systolic blood pressure and risk of coronary events in elderly treated hypertensive patients. Subjects were divided according
to tertiles of MS of systolic blood pressure of the population as a whole, by
dipping status (nondippers are at increased risk than dippers) and by
group-specific tertiles of morning surge of systolic blood pressure in dippers and nondippers because these groups have different MS of blood pressure. In elderly treated
hypertensive patients, high MS of systolic BP predicts coronary events
in dippers but not in nondippers. Nondippers, however, show higher
risk of coronary events independently of morning surge in systolic blood pressure.

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

Dr. Pierdomenico: Blood pressure should be better controlled after awakening in dippers with high morning surge and during the night in nondippers in order to better prevent
cardiovascular events. Continue reading

Epigenetic Biomarker May Improve Cervical Cancer Screening

Christos Nikolaidis Ph.D. Laboratory of Pharmacology Medical School, Democritus University of Thrace Dragana, Alexandroupolis GreeceMedicalResearch.com Interview with:
Christos Nikolaidis Ph.D.
Laboratory of Pharmacology
Medical School, Democritus University of Thrace
Dragana, Alexandroupolis Greece

Medical Research: What is the background for this study?

Response: Epigenetic changes are part of the natural history of cervical neoplasia. Tracking these changes at the molecular level is necessary for understanding disease progression, response to treatment and prognosis. Epigenetic biomarkers can potentially assess the stage of cervical intraepithelial neoplasia (CIN). This information can be used for screening purposes, to improve the overall quality of cervical cancer diagnostics.

Medical Research: What are the main findings?

Response: Paired boxed 1 (PAX1) gene methylation status has been widely used as a biomarker for cervical cancer screening.  We have conducted a meta-analysis of the diagnostic test accuracy of PAX1 methylation, on moderate cervical dysplasia or worse (CIN2+) versus normal epithelium, and severe cervical dysplasia or worse (CIN3+) versus normal epithelium, for a total population of 1385 women. The results of this assay were generally satisfactory for CIN2+ vs normal, and extremely satisfactory for CIN3+ vs normal (Sensitivity=0.77, Specificity=0.92, AUC=0.931). This raises the possibility of utilizing this biomarker to improve current diagnostic protocols.

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Genes May Explain Why Smarter People Live Longer

Dr. Rosalind Arden Centre for Philosophy of Natural & Social Science London School of Economics LondonMedicalResearch.com Interview with:
Dr. Rosalind Arden
Centre for Philosophy of Natural & Social Science
London School of Economics
London

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

Dr. Arden: We’ve known for a while that people who score higher on IQ-type tests tend to live longer. A study published in the British Medical Journal (Whalley & Deary, 2001) examined intelligence in childhood and later survival. People born in Scotland in 1921 took an IQ-type test at age 11 in 1932. Those with higher test scores were more likely to survive to age 76.

What we haven’t known is ‘why?’ One possibility is that advantages from being raised in a wealthier family may enhance intelligence and health – leading to brighter people living longer. Another possibility is that many genes that influence brains also influence bodies. If well-built brains co-occur with well-built bodies, that could also explain the link. These are only two of several possible explanations. We aimed to test whether genes caused the link between intelligence and life-expectancy.

We found

1) the link between intelligence and life expectancy is positive but small.

2) The cause of the link is almost all genetic.

We found this by examining differences within twin pairs. Twins offer a quasi-natural experiment because they share many features of the environment that are often thought (mistakenly) to cause differences between people. And marvelously, for science there are two kinds of twins, with known genetic relatedness (100 % or 50%). This give us a means to test questions about the cause of differences in a population, as well as the causes of correlations among traits within a population.

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Patients With Blood Cancers May Need More Support At End Of Life

Prof David C Currow Discipline of Palliative and Supportive Services Flinders University Adelaide, SA, AustraliaMedicalResearch.com Interview with:
Prof David C Currow
Discipline of Palliative and Supportive Services
Flinders University
Adelaide, SA, Australia

Medical Research: What is the background for this study?

Prof. Currow: This study grew out of a desire to better understand the symptom burden experienced by people with hematological malignancies at the end of life. This has been very poorly documented and although there are lots of strong opinions, there are very few data at a population level.

Medical Research: What are the main findings?

Prof. Currow: The main finding is that community-dwelling people with hematological malignancies at the end of life have a burden of symptoms that looked almost identical to people with solid tumours. Given much lower rates of access to the hospice and palliative care, this suggests that these people and their family caregivers are missing out on opportunities for better symptom control and better support. Continue reading

Cancer Drug Can Activate HIV Reservoirs To Target For Eradication

Dr. Satya Dandekar PhD Professor and Chair Department of Medical Microbiology and Immunology UC DavisMedicalResearch.com Interview with:
Dr. Satya Dandekar PhD
Professor and Chair
Department of Medical Microbiology and Immunology
UC Davis

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

Dr. Dandekar: Current anti-retroviral therapy is effective in suppressing HIV replication and enhancing immune functions in HIV infected individuals. However, it fails to eradicate the latent HIV reservoirs. Therapy interruption leads to a rapid viral rebound in these patients.  Eradication of latent HIV reservoirs is essential to achieve HIV cure. A “shock and kill” strategy for HIV cure has been proposed that involves reactivation of latent viral reservoirs using latency reversal agents (LRA) and eradication by the immune response. This highlights the need to identify potent LRAs to optimally activate latent HIV reservoirs so that immune surveillance and clearance mechanisms can be effectively engaged in the process of viral eradication. We have found that ingenol-3-angelate (PEP005), an anti-cancer drug can effectively reactivate latent HIV. It is a protein kinase C agonist that activates NF-kB and stimulates HIV expression. In combination with another compound, JQ1, a previously known p-TEFb agonist, the efficacy of PEP005 for HIV reactivation is markedly increased. In addition, ingenol-3-angelate decreases the expression of HIV co-receptors on immune cells, which potentially will help preventing further spread of the virus. The use of ingenol-3-angelate in combination with other latency reversal agents provides an excellent opportunity to optimally activate latent HIV reservoirs and target them for eradication.

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