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#29036654   2017/10/16 Save this To Up

Detection of expanded RNA repeats using thermostable group II intron reverse transcriptase.

Cellular accumulation of repetitive RNA occurs in several dominantly-inherited genetic disorders. Expanded CUG, CCUG or GGGGCC repeats are expressed in myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), or familial amyotrophic lateral sclerosis, respectively. Expanded repeat RNAs (ER-RNAs) exert a toxic gain-of-function and are prime therapeutic targets in these diseases. However, efforts to quantify ER-RNA levels or monitor knockdown are confounded by stable structure and heterogeneity of the ER-RNA tract and background signal from non-expanded repeats. Here, we used a thermostable group II intron reverse transcriptase (TGIRT-III) to convert ER-RNA to cDNA, followed by quantification on slot blots. We found that TGIRT-III was capable of reverse transcription (RTn) on enzymatically synthesized ER-RNAs. By using conditions that limit cDNA synthesis from off-target sequences, we observed hybridization signals on cDNA slot blots from DM1 and DM2 muscle samples but not from healthy controls. In transgenic mouse models of DM1 the cDNA slot blots accurately reflected the differences of ER-RNA expression across different transgenic lines, and showed therapeutic reductions in skeletal and cardiac muscle, accompanied by improvements of the DM1-associated splicing defects. TGIRT-III was also active on CCCCGG- and GGGGCC-repeats, suggesting that ER-RNA analysis is feasible for several repeat expansion disorders.

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#29036604   2017/10/16 Save this To Up

Accomplishing reform: successful case studies drawn from the health systems of 60 countries.

Healthcare reform typically involves orchestrating a policy change, mediated through some form of operational, systems, financial, process or practice intervention. The aim is to improve the ways in which care is delivered to patients. In our book 'Health Systems Improvement Across the Globe: Success Stories from 60 Countries', we gathered case-study accomplishments from 60 countries. A unique feature of the collection is the diversity of included countries, from the wealthiest and most politically stable such as Japan, Qatar and Canada, to some of the poorest, most densely populated or politically challenged, including Afghanistan, Guinea and Nigeria. Despite constraints faced by health reformers everywhere, every country was able to share a story of accomplishment-defining how their case example was managed, what services were affected and ultimately how patients, staff, or the system overall, benefited. The reform themes ranged from those relating to policy, care coverage and governance; to quality, standards, accreditation and regulation; to the organization of care; to safety, workforce and resources; to technology and IT; through to practical ways in which stakeholders forged collaborations and partnerships to achieve mutual aims. Common factors linked to success included the 'acorn-to-oak tree' principle (a small scale initiative can lead to system-wide reforms); the 'data-to-information-to-intelligence' principle (the role of IT and data are becoming more critical for delivering efficient and appropriate care, but must be converted into useful intelligence); the 'many-hands' principle (concerted action between stakeholders is key); and the 'patient-as-the-pre-eminent-player' principle (placing patients at the centre of reform designs is critical for success).

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#29036603   2017/10/16 Save this To Up

Identification of optimal reference genes for transcriptomic analyses in normal and diseased human heart.

Quantitative real-time RT-PCR (RT-qPCR) has become the method of choice for mRNA quantification, but requires an accurate normalization based on the use of reference genes showing invariant expression across various pathological conditions. Only few data exist on appropriate reference genes for the human heart. The objective of this study was to determine a set of suitable reference genes in human atrial and ventricular tissues, from right and left cavities in control and in cardiac diseases.

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#29036595   2017/10/16 Save this To Up

Persistent in vivo cytogenetic effects of radioiodine therapy: a 21-year follow-up study using multicolor FISH.

Our previous studies demonstrated the cytogenetic effects in the peripheral blood lymphocytes of a 34-year-old male patient who received ablative radioactive 131iodine therapy (RIT) on two different occasions in 1992 and 1994. Assessment of RIT-induced chromosomal damage by the cytokinesis-blocked micronucleus assay (CBMN) showed the persistence of elevated micronucleus frequency in this patient for more than two decades since the first RIT. Subsequent cytogenetic analysis performed in 2012 revealed both stable and unstable aberrations, whose frequencies were higher than the baseline reported in the literature. Here, we report the findings of our recent cytogenetic analysis peformed in 2015 on this patient using the multicolor fluorescence in situ hybridization (mFISH) technique. Our results showed that both reciprocal and non-reciprocal translocations persisted at higher frequencies in the patient than those reported in 2012. Persistence of structural aberrations for more than two decades indicate that these aberrations might have originated from long-lived T-lymphocytes or hematopoietic stem cells. Our study suggests that the long-term persistence of chromosome translocations in circulating lymphocytes can be useful for monitoring the extent of RIT-induced chromosomal instability several years after exposure and for estimating the cumulative absorbed dose after multiple RITs for retrospective biodosimetry purposes. This is perhaps the first and longest follow-up study documenting the persistence of cytogenetic damage for 21 years after internal radiation exposure.

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#29036572   2017/10/16 Save this To Up

DOSE EFFECT OF THE 33S(n,α) 30SI REACTION IN BNCT USING THE NEW n_TOF-CERN DATA.

33S is a stable isotope of sulphur which is being studied as a potential cooperative target for Boron Neutron Capture Therapy (BNCT) in accelerator-based neutron sources because of its large (n,α) cross section in the epithermal neutron energy range. Previous measurements resolved the resonances with a discrepant description of the lowest-lying and strongest one (at 13.5 keV). However, the evaluations of the major databases do not include resonances, except EAF-2010 which shows smaller values in this range than the experimental data. Furthermore, the glaring lack of data below 10 keV down to thermal (25.3 meV) has motivated a new measurement at n_TOF at CERN in order to cover the whole energy range. The inclusion of this new 33S(n,α) cross section in Monte Carlo simulations provides a more accurate estimation of the deposited kerma rate in tissue due to the presence of 33S. The results of those simulations represent the goal of this work.

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#29036483   2017/10/16 Save this To Up

A Decade of War: Prospective Trajectories of Post-Traumatic Stress Disorder Symptoms Among Deployed US Military Personnel and the Influence of Combat Exposure.

Post-traumatic stress disorder (PTSD) is a common psychiatric disorder among service members and veterans. The clinical course of PTSD varies across individuals, and patterns of symptom development have yet to be clearly delineated. Previous studies have been limited by convenience sampling, short follow-up periods, and inability to account for combat-related trauma. To determine the trajectories of PTSD symptoms among deployed military personnel with and without combat exposure, we used data from a population-based representative sample of 8,178 US service members participating in the Millennium Cohort Study from 2001-2011. Using latent class growth mixture modeling, trajectories of PTSD symptoms were determined in the total sample and in individuals with and without combat exposure. Four trajectories of PTSD were characterized: resilient, pre-existing, new-onset, and moderate-stable. Across all trajectories combat deployed service members diverged from non-combat deployed service members after a single deployment, and generally had higher PTSD symptoms. Based on the models, nearly 90% of those without combat and 80% of those with combat exposure remained resilient over the 10-year period. Findings demonstrate the clinical course of PTSD symptoms have heterogeneous patterns of development, but that combat exposure is uniformly associated with poorer mental health.

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#29036460   2017/10/16 Save this To Up

RADON EXHALATION FROM SOIL AND ITS DEPENDENCE FROM ENVIRONMENTAL PARAMETERS.

An automatic measuring apparatus called exhalometer for measurement of the radon exhalation rate from soil is introduced. It consists of a pneumatic driven accumulation chamber with an open bottom, a PC-based control system, six Lucas cells for radon measurement and sensors for environmental parameters. It allows moving the accumulation chamber and hereby opening or closing it. The exhalation rate is determined through the increase of radon in the accumulation chamber. For studying exhalation and the affecting factors, the exhalometer was placed at an undisturbed meadow for the entire year of 2015. The daily radon exhalation rate ranges from 2.5 to 50.7 Bq m-2 h-1 with an average of 25.3 Bq m-2 h-1. The exhalation rate shows daily and seasonal variations with its maximum in the afternoon and in spring. The dependence on several environmental parameters is discussed. The stable performance indicates the system's fitness for long-term measurements.

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#29036332   2017/10/16 Save this To Up

Sensitivity to Physical Activity Predicts Daily Activity Among Pain-Free Older Adults.

Prior research indicates that older adults with knee osteoarthritis have increased sensitivity to physical activity (SPA) and respond to physical activities of stable intensity with increases in pain. Whether SPA is present in healthy older adults without chronic pain and predicts functional outcomes remains relatively unexplored. The purpose of this study was to determine the degree of SPA in healthy older adults in response to a standardized walking task, and whether SPA was associated with temporal summation of pain, pain-related fear of movement, and functional outcomes.

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#29036269   2017/10/16 Save this To Up

Longitudinal blood pressure changes and kidney function decline in persons without chronic kidney disease: Findings from the MESA study.

While changes in blood pressure (BP) are independently associated with cardiovascular events, less is known about the association between changes in BP and subsequent changes in renal function in adults with an estimated glomerular filtration rate (eGFR) of > 60 ml/min/1.73 m2.

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#29036251   2017/10/16 Save this To Up

An Adhesive Patch-Based Skin Biopsy Device for Molecular Diagnostics and Skin Microbiome Studies.

A number of diagnoses in clinical dermatology are currently histopathologically confirmed and this image recognition-based confirmation generally requires surgical biopsies. The increasing ability of molecular pathology to corroborate or correct a clinical diagnosis based on objective gene expression, mutation analysis, or molecular microbiome data is on the horizon and would be further supported by a tool or procedure to collect samples non-invasively. This study characterizes such a tool in form of a 'bladeless' adhesive patch-based skin biopsy device.

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