Ιατρικά Άρθρα Αλέξανδρος Γ. Σφακιανάκης: 11/05/17

Κυριακή 5 Νοεμβρίου 2017

Vertical distributions and source identification of the radionuclides 239Pu and 240Pu in the sediments of the Liao River estuary, China

Publication date: January 2018
Source:Journal of Environmental Radioactivity, Volume 181
Author(s): Kexin Zhang, Shaoming Pan, Zhiyong Liu, Guosheng Li, Yihong Xu, Yongpei Hao
Activity concentration of plutonium (Pu) and its isotopic compositions are extensively used for measuring transport processes of Pu and identifying its source. We investigated the spatial distribution characteristics of ^239+240Pu activity concentrations and ²⁴⁰Pu/²³⁹Pu atom ratio in several sediment cores collected from the Liao River coastal zone. Additionally, we calculated the ^239+240Pu inventories and based on the ²⁴⁰Pu/²³⁹Pu atom ratio to trace Pu source. The activity concentrations of ^239+240Pu in surface sediments of the Liao River estuary ranged between 0.103 ± 0.008 and 0.978 ± 0.035 mBq/g, with an average of 0.294 ± 0.024 mBq/g. The ²⁴⁰Pu/²³⁹Pu atom ratios, ranging from 0.173 ± 0.047 to 0.215 ± 0.061 (mean: 0.188 ± 0.049 (1σ)), were consistent with global fallout value, which indicates the global atmospheric fallout is the main source of Pu in sediment cores from the both sides of Liao River estuary. As for the tidal flat core LT-2, the mean ²⁴⁰Pu/²³⁹Pu atom ratio, slightly higher than that of the global fallout value, was 0.217 ± 0.050. Such pattern of Pu isotopic compositions indicated that Pu on the tidal flat in the Liao River estuary is sourced from a combination of global fallout and close-in fallout from the PPG by ocean currents transporting. And by using a two end-member mixing model, the results indicate the relative contribution of the PPG close-in fallout to core LT-2 is round 27% and 73% can be attributed to global fallout and river input. Therefore, these results clearly indicate that the direct global fallout is the main source of Pu in the Liao River estuary.

Graphical abstract

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Sources of inflow and nature of redistribution of 90Sr in the salt lakes of the Crimea

Publication date: Available online 5 November 2017
Source:Journal of Environmental Radioactivity
Author(s): N.Yu. Mirzoyeva, S.I. Arkhipova, N.V. Kravchenko
At the first time for the period after the Chernobyl NPP accident the nature of the redistribution of the ⁹⁰Sr concentrations in components of the ecosystems of the salt lakes of the Crimea were identified and described. Concentration of ⁹⁰Sr in water of the salt lakes depends on the sources of the inflow this radionuclide into aquatic ecosystems and salinity level of lakes water. Until April 2014 the flow of the Dnieper river water through the Northern-Crimean canal was more important factor of contamination of salt lakes of the Crimea by ⁹⁰Sr, than atmospheric fallout of this radionuclide after the Chernobyl NPP accident. Concentrations of ⁹⁰Sr in water of the salt lakes of the Crimea exceeded 2.4–156.5 times its concentrations in their bottom sediments. The ⁹⁰Sr dose commitments to hydrophytes, which were sampled from the salt lakes of the Crimea have not reached values which could impact them during entire the after-accident period.

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The validity of arterial measurements in a South African embalmed body population.

The validity of arterial measurements in a South African embalmed body population.

Surg Radiol Anat. 2017 Nov 03;:

Authors: Schoeman M, van Schoor A, Suleman F, Louw L, du Toit P

Abstract
INTRODUCTION: Knowledge of the normal arterial diameter at a given anatomical point is the first step toward quantifying the severity of cardiovascular diseases. According to several studies, parameters such as weight, height, age and sex can explain morphometric variations in arterial anatomy that are observed in a population. Before the development of a reference database against which to compare the diameters of arteries in a variety of pathological conditions, the compatibility between embalmed body measurements and computed tomography (CT) measurements must first be established.
PURPOSE: The aim of this study was to compare embalmed body measurements and CT measurements at 19 different arterial sites to establish whether embalmed body measurements are a true reflection of a living population.
METHODS: A total of 154 embalmed bodies were randomly selected from the Department of Anatomy at the University of Pretoria and 36 embalmed bodies were randomly selected from the Department of Human Anatomy at the University of Limpopo, Medunsa Campus. Dissections were performed on the embalmed body sample and the arterial dimensions were measured with a mechanical dial-sliding caliper (accuracy of 0.01 mm). 30 CT images for each of the 19 arterial sites were retrospectively selected from the database of radiographic images at the Department of Radiology, Steve Biko Academic Hospital. Radiant, a Digital Imaging and Communications in Medicine (DICOM) viewer was used to analyze the CT images.
RESULTS: The only statistically significant differences between the embalmed body measurements and CT measurements were found in the left common carotid- and the left subclavian arteries. The null hypothesis of no statistically significant difference between the embalmed body and CT measurements was accepted since the P value indicated no significant difference for 87% of the measurements, the exception being the left common carotid- and the left subclavian arteries.
CONCLUSIONS: With the exception of two measurements, measurements in embalmed bodies and living people are interchangeable and concerns regarding the effect of distortion and shrinkage are unfounded. Even small changes in arterial diameter greatly influence blood flow and blood pressure, which contribute to undesirable clinical outcomes such as aortic aneurysms and aortic dissections. This study completes the first step towards the development of a reference database against which to compare the diameters of arteries in a variety of pathological conditions in a South African population.

PMID: 29101462 [PubMed - as supplied by publisher]

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A confounding rib variation: bilateral symmetric aberrant posterior rib articulations and bridgings.

A confounding rib variation: bilateral symmetric aberrant posterior rib articulations and bridgings.

Surg Radiol Anat. 2017 Nov 03;:

Authors: Bayramoglu Z, Yilmaz R, Caliskan E, Buyuksahin G, Bulut F, Aliyev S, Adaletli I

Abstract
INTRODUCTION: Although mild bone angulation with osseous enlargement often suggests fractures with callus formation, in some cases the diagnosis is synchondrosis.
CASE REPORT: We present a rare variation of the chest wall in a 15-year-old male with a history of lymphoma. Bilateral multi-level posterior rib enlargements revealing mild (18)F-fluorodeoxyglucose uptake were detected via positron-emission tomography/computed tomography. The variations were identified as healing fractures, although the more accurate diagnosis was determined to be multi-level posterior rib synchondroses with consecutive bridgings. Although variant bone anatomies are commonly seen in radiological practice, such multiple symmetrical posterior rib synchondroses associated with consecutive bridgings and articulations have not been clearly demonstrated before.
CONCLUSION: Awareness of such a rare combination of a well-known variation is crucial for radiologists to exclude malignancies, possibility of fracture and suspicion of child abuse.

PMID: 29101461 [PubMed - as supplied by publisher]

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Ioannis N. Mavridis: Stereotactic brain microanatomy: mathematical principles and applications (Neuroanatomy Research at the Leading Edge) : Nova Biomedical - Nova Science Publishers, New York, 2017, xxxvi + 128 p, 33 illustrations, format 15.6 × 23 cm, ISBN: 978-1-53612-366-1, ISBN: 978-1-53612-380-7 (e-Book).

Ioannis N. Mavridis: Stereotactic brain microanatomy: mathematical principles and applications (Neuroanatomy Research at the Leading Edge) : Nova Biomedical - Nova Science Publishers, New York, 2017, xxxvi + 128 p, 33 illustrations, format 15.6 × 23 cm, ISBN: 978-1-53612-366-1, ISBN: 978-1-53612-380-7 (e-Book).

Surg Radiol Anat. 2017 Nov 03;:

Authors: Pyrgelis ES

PMID: 29101460 [PubMed - as supplied by publisher]

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Sensitivity of a prompt-gamma slit-camera to detect range shifts for proton treatment verification

Publication date: Available online 4 November 2017
Source:Radiotherapy and Oncology
Author(s): Lena Nenoff, Marlen Priegnitz, Guillaume Janssens, Johannes Petzoldt, Patrick Wohlfahrt, Anna Trezza, Julien Smeets, Guntram Pausch, Christian Richter
Background and purposeA prompt-gamma imaging (PGI) slit-camera was recently applied successfully in clinical proton treatments using pencil beam scanning (PBS) and double scattering (DS). However, its full capability under clinical conditions has still to be systematically evaluated. Here, the performance of the slit-camera is systematically assessed in well-defined error scenarios using realistic treatment deliveries to an anthropomorphic head phantom.Materials and methodsThe sensitivity and accuracy to detect introduced global and local range shifts with the slit-camera was investigated in PBS and DS irradiations. For PBS, measured PGI information of shifted geometries were compared spot-wise with un-shifted PGI information derived from either a reference measurement or a treatment-plan-based simulation. Furthermore, for DS and PBS the integral PGI signal of the whole field was evaluated.ResultsDeviations from the treatment plan were detected with an accuracy better than 2 mm in PBS. The PGI simulation accuracy was well below 1 mm. Interfractional comparisons are more affected by measurement noise. The field-integral PGI sum signal allows the detection of global shifts in DS.ConclusionsDetection of global and local range shifts under close-to-clinical conditions is possible with the PGI slit-camera. Especially for PBS, high sensitivity and high accuracy in shift detection were found.

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Reactivity and sensitivity of commercially available influenza rapid diagnostic tests in Japan.

Reactivity and sensitivity of commercially available influenza rapid diagnostic tests in Japan.

Sci Rep. 2017 Nov 03;7(1):14483

Authors: Sakai-Tagawa Y, Yamayoshi S, Kawakami C, Le MQ, Uchida Y, Saito T, Nidom CA, Humaira I, Toohey-Kurth K, Arafa AS, Liu MT, Shu Y, Kawaoka Y

Abstract
Seasonal influenza virus routinely causes epidemic infections throughout the world. Sporadic infections by H5N1, H5N6, and H7N9 viruses are also reported. To treat patients suffering from such viral infections, broadly reactive and highly sensitive influenza rapid diagnostic tests (IRDTs) are required. Here, we examined the reactivity and sensitivity of 25 IRDTs available in Japan for the detection of seasonal H1N1pdm09, H3N2, and type B viruses, as well as highly pathogenic H5 and H7 viruses. All of the IRDTs tested detected the seasonal viruses and H5 and H7 viruses albeit with different sensitivities. Several IRDTs detected the H5 and H7 viruses and the seasonal viruses with similar (high) sensitivity.

PMID: 29101372 [PubMed - in process]

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Plasma amino acid profile associated with fatty liver disease and co-occurrence of metabolic risk factors.

Plasma amino acid profile associated with fatty liver disease and co-occurrence of metabolic risk factors.

Sci Rep. 2017 Nov 03;7(1):14485

Authors: Yamakado M, Tanaka T, Nagao K, Imaizumi A, Komatsu M, Daimon T, Miyano H, Tani M, Toda A, Yamamoto H, Horimoto K, Ishizaka Y

Abstract
Fatty liver disease (FLD) increases the risk of diabetes, cardiovascular disease, and steatohepatitis, which leads to fibrosis, cirrhosis, and hepatocellular carcinoma. Thus, the early detection of FLD is necessary. We aimed to find a quantitative and feasible model for discriminating the FLD, based on plasma free amino acid (PFAA) profiles. We constructed models of the relationship between PFAA levels in 2,000 generally healthy Japanese subjects and the diagnosis of FLD by abdominal ultrasound scan by multiple logistic regression analysis with variable selection. The performance of these models for FLD discrimination was validated using an independent data set of 2,160 subjects. The generated PFAA-based model was able to identify FLD patients. The area under the receiver operating characteristic curve for the model was 0.83, which was higher than those of other existing liver function-associated markers ranging from 0.53 to 0.80. The value of the linear discriminant in the model yielded the adjusted odds ratio (with 95% confidence intervals) for a 1 standard deviation increase of 2.63 (2.14-3.25) in the multiple logistic regression analysis with known liver function-associated covariates. Interestingly, the linear discriminant values were significantly associated with the progression of FLD, and patients with nonalcoholic steatohepatitis also exhibited higher values.

PMID: 29101348 [PubMed - in process]

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Association between Ideal Cardiovascular Health Metrics and Suboptimal Health Status in Chinese Population.

Association between Ideal Cardiovascular Health Metrics and Suboptimal Health Status in Chinese Population.

Sci Rep. 2017 Nov 03;7(1):14975

Authors: Wang Y, Liu X, Qiu J, Wang H, Liu D, Zhao Z, Song M, Song Q, Wang X, Zhou Y, Wang W

Abstract
Suboptimal health status (SHS) is a physical state between health and illness, and previous studies suggested that SHS is associated with majority components of cardiovascular health metrics defined by American Heart Association (AHA). We investigated the association between SHS and cardiovascular health metrics in a cross-sectional analysis of China suboptimal health cohort study (COACS) consisting of 4313 participants (60.30% women) aged from 18 to 65 years old. The respective prevalence of SHS is 7.10%, 9.18%, 10.04% and 10.62% in the first, second, third and fourth quartiles of ideal cardiovascular health (CVH) metrics (P for trend = 0.012). Participants in the largest quartile of ideal CVH metrics show a lower likelihood of having optimal SHS score compared to those in the smallest quartile (odds ratio (OR), 0.43; 95% confidence interval (CI), 0.32-0.59), after adjusting for age, gender, marital status, alcohol consumption, income level and education. Four metrics (smoking, physical inactivity, poor dietary intake and ideal control of blood pressure are significantly correlated with the risk of SHS. The present study suggests that ideal CVH metrics are associated with a lower prevalence of SHS, and the combined evaluation of SHS and CVH metrics allows the risk classification of cardiovascular disease, and thus consequently contributes to the prevention of cardiovascular diseases.

PMID: 29101345 [PubMed - in process]

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Cell-permeable organic fluorescent probes for live-cell long-term super-resolution imaging reveal lysosome-mitochondrion interactions.

Cell-permeable organic fluorescent probes for live-cell long-term super-resolution imaging reveal lysosome-mitochondrion interactions.

Nat Commun. 2017 Nov 03;8(1):1307

Authors: Han Y, Li M, Qiu F, Zhang M, Zhang YH

Abstract
Characterizing the long-term nanometer-scale interactions between lysosomes and mitochondria in live cells is essential for understanding their functions but remains challenging due to limitations of the existing fluorescent probes. Here, we develop cell-permeable organic fluorescent probes for lysosomes with excellent specificity and high photostability. We also use an existing Atto 647N dye with high brightness and excellent photostability to achieve specific labeling of mitochondria in live cells. Using these probes, we obtain dual-color structured illumination microscopy (SIM) images of dynamic physical lysosome-mitochondrion interactions in live cells at an ~90-nm resolution over a long time course of ~13 min. We successfully record the consecutive dynamic processes of lysosomal fusion and fission, as well as four types of physical lysosome-mitochondrion interactions by super-resolution imaging. Our probes provide an avenue for understanding the functions and the dynamic interplay of lysosomes and mitochondria in live cells.

PMID: 29101340 [PubMed - in process]

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Comparative transcriptome analysis reveals potentially novel roles of Homeobox genes in adipose deposition in fat-tailed sheep.

Comparative transcriptome analysis reveals potentially novel roles of Homeobox genes in adipose deposition in fat-tailed sheep.

Sci Rep. 2017 Nov 03;7(1):14491

Authors: Kang D, Zhou G, Zhou S, Zeng J, Wang X, Jiang Y, Yang Y, Chen Y

Abstract
Adipose tissues are phenotypically, metabolically and functionally heterogeneous based on the sites of their deposition. Undesirable fat deposits in the body are often detrimental to animal and human health. To unravel the potential underlying mechanisms governing accumulation of adipose tissues in various regions of the body, i.e., subcutaneous (SAT), visceral (VAT) and tail (TAT), we profiled transcriptomes from Tan sheep, a Chinese indigenous breed with notable fat tail using RNA-seq. Upon comparison, we identified a total of 1,058 differentially expressed genes (DEGs) between the three adipose types (218, 324, and 795 in SAT/VAT, SAT/TAT, and VAT/TAT, respectively), from which several known key players were identified that are involved in lipid metabolic process, Wnt signals, Vitamin A metabolism, and transcriptional regulation of adipocyte differentiation. We also found that many elevated genes in VAT were notably enriched for key biological processes such as cytokine secretion, signaling molecule interaction and immune systems. Several developmental genes including HOXC11, HOXC12 and HOXC13, and adipose-expressed genes in the tail region, such as HOTAIR_2, HOTAIR_3 and SP9 were specially highlighted, indicating their strong associations with tail fat development in fat-tailed sheep. Our results provide new insight into exploring the specific fat deposition in tail, also contribute to the understanding of differences between adipose depots.

PMID: 29101335 [PubMed - in process]

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Mode of Tolerance Induction and Requirement for Aire Are Governed by the Cell Types That Express Self-Antigen and Those That Present Antigen.

Mode of Tolerance Induction and Requirement for Aire Are Governed by the Cell Types That Express Self-Antigen and Those That Present Antigen.

J Immunol. 2017 Nov 03;:

Authors: Mouri Y, Ueda Y, Yamano T, Matsumoto M, Tsuneyama K, Kinashi T, Matsumoto M

Abstract
Aire controls the fate of autoreactive thymocytes (i.e., clonal deletion or development into regulatory T cells [Tregs]) through transcriptional control of the expression of tissue-restricted self-antigens (TRAs) from medullary thymic epithelial cells (mTECs) and bone marrow (BM)-derived cells. Although TRAs expressed by mTECs and BM-derived cells are suggested to complement each other to generate a full spectrum of TRAs, little is known about the relative contribution of TRAs from each component for establishment of self-tolerance. Furthermore, the precise role of Aire in specific types of Aire-expressing APCs remains elusive. We have approached these issues by generating two different types of transgenic mouse (Tg) model, which express a prefixed model self-antigen driven by the insulin promoter or the Aire promoter. In the insulin-promoter Tg model, mTECs alone were insufficient for clonal deletion, and BM-derived APCs were required for this action by utilizing Ag transferred from mTECs. In contrast, mTECs alone were able to induce Tregs, although at a much lower efficiency in the absence of BM-derived APCs. Importantly, lack of Aire in mTECs, but not in BM-derived APCs, impaired both clonal deletion and production of Tregs. In the Aire-promoter Tg model, both mTECs and BM-derived APCs could independently induce clonal deletion without Aire, and production of Tregs was impaired by the lack of Aire in mTECs, but not in BM-derived APCs. These results suggest that the fate of autoreactive thymocytes together with the requirement for Aire depend on the cell types that express self-antigens and the types of APCs involved in tolerance induction.

PMID: 29101311 [PubMed - as supplied by publisher]

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Confluence of Cultural Context and Technological Innovation to Reduce Cardiovascular Disparities in India.

Confluence of Cultural Context and Technological Innovation to Reduce Cardiovascular Disparities in India.

Circ Cardiovasc Qual Outcomes. 2017 Nov;10(11):

Authors: Sinha SS, Prabhakaran D, Chopra V

PMID: 29101271 [PubMed - in process]

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Tuberculosis Treatment Adherence of Patients in Kosovo

Setting. The poor patient adherence in tuberculosis (TB) treatment is considered to be one of the most serious challenges which reflect the decrease of treatment success and emerging of the Multidrug Resistance-TB (MDR-TB). To our knowledge, the data about patients’ adherence to anti-TB treatment in our country are missing. Objective. This study was aimed to investigate the anti-TB treatment adherence rate and to identify factors related to eventual nonadherence among Kosovo TB patients. Design. This study was conducted during 12 months, and the survey was a descriptive study using the standardized questionnaires with total 324 patients. Results. The overall nonadherence for TB patient cohort was 14.5%, 95% CI (0.109–0.188). Age and place of residence are shown to have an effect on treatment adherence. Moreover, the knowledge of the treatment prognosis, daily dosage, side effects, and length of treatment also play a role. This was also reflected in knowledge regarding compliance with regular administration of TB drugs, satisfaction with the treatment, interruption of TB therapy, and the professional monitoring in the administration of TB drugs. Conclusion. The level of nonadherence TB treatment in Kosovar patients is not satisfying, and more health care worker’s commitments need to be addressed for improvement.

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Effects of a liquefied petroleum gas stove intervention on pollutant exposure and adult cardiopulmonary outcomes (CHAP): study protocol for a randomized controlled trial.

Effects of a liquefied petroleum gas stove intervention on pollutant exposure and adult cardiopulmonary outcomes (CHAP): study protocol for a randomized controlled trial.

Trials. 2017 Nov 03;18(1):518

Authors: Fandiño-Del-Rio M, Goodman D, Kephart JL, Miele CH, Williams KN, Moazzami M, Fung EC, Koehler K, Davila-Roman VG, Lee KA, Nangia S, Harvey SA, Steenland K, Gonzales GF, Checkley W, Cardiopulmonary outcomes and Household Air Pollution trial (CHAP) Trial Investigators

Abstract
BACKGROUND: Biomass fuel smoke is a leading risk factor for the burden of disease worldwide. International campaigns are promoting the widespread adoption of liquefied petroleum gas (LPG) in resource-limited settings. However, it is unclear if the introduction and use of LPG stoves, in settings where biomass fuels are used daily, reduces pollution concentration exposure, improves health outcomes, or how cultural and social barriers influence the exclusive adoption of LPG stoves.
METHODS: We will conduct a randomized controlled, field intervention trial of LPG stoves and fuel distribution in rural Puno, Peru, in which we will enroll 180 female participants aged 25-64 years and follow them for 2 years. After enrollment, we will collect information on sociodemographic characteristics, household characteristics, and cooking practices. During the first year of the study, LPG stoves and fuel tanks will be delivered to the homes of 90 intervention participants. During the second year, participants in the intervention arm will keep their LPG stoves, but the gas supply will stop. Control participants will receive LPG stoves and vouchers to obtain free fuel from distributors at the beginning of the second year, but gas will not be delivered. Starting at baseline, we will collect longitudinal measurements of respiratory symptoms, pulmonary function, blood pressure, endothelial function, carotid artery intima-media thickness, 24-h dietary recalls, exhaled carbon monoxide, quality-of-life indicators, and stove-use behaviors. Environmental exposure assessments will occur six times over the 2-year follow-up period, consisting of 48-h personal exposure and kitchen concentration measurements of fine particulate matter and carbon monoxide, and 48-h kitchen concentrations of nitrogen dioxide for a subset of 100 participants.
DISCUSSION: Findings from this study will allow us to better understand behavioral patterns, environmental exposures, and cardiovascular and pulmonary outcomes resulting from the adoption of LPG stoves. If this trial indicates that LPG stoves are a feasible and effective way to reduce household air pollution and improve health, it will provide important information to support widespread adoption of LPG fuel as a strategy to reduce the global burden of disease.
TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02994680 , Cardiopulmonary Outcomes and Household Air Pollution (CHAP) Trial. Registered on 28 November 2016.

PMID: 29100550 [PubMed - in process]

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Robotic-assisted modified radical neck dissection using a bilateral axillo-breast approach (robotic BABA MRND) for papillary thyroid carcinoma with lateral lymph node metastasis.

Robotic-assisted modified radical neck dissection using a bilateral axillo-breast approach (robotic BABA MRND) for papillary thyroid carcinoma with lateral lymph node metastasis.

Surg Endosc. 2017 Nov 03;:

Authors: Yu HW, Chai YJ, Kim SJ, Choi JY, Lee KE

Abstract
BACKGROUND: Although safe in patients with papillary thyroid carcinoma (PTC), robotic thyroidectomy using a bilateral axillo-breast approach (BABA) has not been frequently performed in patients with advanced PTC. This study describes surgical outcomes in patients with PTC and lymph node metastasis (LNM) in lateral neck compartment who underwent robotic-assisted modified radical neck dissection with BABA (robotic BABA MRND).
METHODS: The medical records of patients with PTC and lateral LNM who underwent robotic BABA MRND from March 2010 to July 2016 were retrospectively reviewed.
RESULTS: Fifteen patients, 14 women and 1 man, of mean age 37.1 ± 9.3 years, were enrolled. Mean operation time was 272.7 ± 33.8 min. A mean 20.7 ± 7.2 lymph nodes were retrieved from the lateral neck compartment, with a mean 5.3 ± 4.4 lymph nodes being metastatic. The rates of transient and permanent hypocalcemia were 46.7 and 0%, respectively, and the rates of transient and permanent vocal cord palsy were 6.7 and 0%, respectively. Fourteen patients (93.3%) had stimulated thyroglobulin concentrations below 2 ng/mL after the first treatment with radioactive iodine.
CONCLUSIONS: Robotic BABA MRND could be safely performed and may be a good surgical option in selected patients with PTC and lateral LNM.

PMID: 29101559 [PubMed - as supplied by publisher]

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A cognitive-behavioral and mindfulness-based group sleep intervention improves behavior problems in at-risk adolescents by improving perceived sleep quality.

A cognitive-behavioral and mindfulness-based group sleep intervention improves behavior problems in at-risk adolescents by improving perceived sleep quality.

Behav Res Ther. 2017 Oct 12;99:147-156

Authors: Blake MJ, Snoep L, Raniti M, Schwartz O, Waloszek JM, Simmons JG, Murray G, Blake L, Landau ER, Dahl RE, Bootzin R, McMakin DL, Dudgeon P, Trinder J, Allen NB

Abstract
OBJECTIVE: The aim of this study was to test whether a cognitive-behavioral and mindfulness-based group sleep intervention would improve behavior problems in at-risk adolescents, and whether these improvements were specifically related to improvements in sleep.
METHOD: Secondary analysis of a randomized controlled trial conducted with 123 adolescent participants (female = 60%; mean age = 14.48, range 12.04-16.31 years) who had high levels of sleep problems and anxiety symptoms. Participants were randomized into either a sleep improvement intervention (n = 63) or an active control "study skills" intervention (n = 60). Participants completed sleep and behavior problems questionnaires, wore an actiwatch and completed a sleep diary for five school nights, both before and after the intervention.
RESULTS: Parallel multiple mediation models showed that postintervention improvements in social problems, attention problems, and aggressive behaviors were specifically mediated by moderate improvements in self-reported sleep quality on school nights, but were not mediated by moderate improvements in actigraphy-assessed sleep onset latency or sleep diary-measured sleep efficiency on school nights.
CONCLUSION: This study provides evidence, using a methodologically rigorous design, that a cognitive-behavioral and mindfulness-based group sleep intervention improved behavior problems in at-risk adolescent by improving perceived sleep quality on school nights. These findings suggest that sleep interventions could be directed towards adolescents with behavior problems.
CLINICAL TRIAL REGISTRATION: This study was part of The SENSE Study (Sleep and Education: learning New Skills Early). URL: ACTRN12612001177842; http://ift.tt/2zfp2SZ.

PMID: 29101843 [PubMed - as supplied by publisher]

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Blocking nocturnal blue light for insomnia: A randomized controlled trial.

Blocking nocturnal blue light for insomnia: A randomized controlled trial.

J Psychiatr Res. 2017 Oct 21;96:196-202

Authors: Shechter A, Kim EW, St-Onge MP, Westwood AJ

Abstract
The use of light-emitting electronic devices before bedtime may contribute to or exacerbate sleep problems. Exposure to blue-wavelength light in particular from these devices may affect sleep by suppressing melatonin and causing neurophysiologic arousal. We aimed to determine if wearing amber-tinted blue light-blocking lenses before bedtime improves sleep in individuals with insomnia. Fourteen individuals (n = 8 females; age ± SD 46.6 ± 11.5 y) with insomnia symptoms wore blue light-blocking amber lenses or clear placebo lenses in lightweight wraparound frames for 2 h immediately preceding bedtime for 7 consecutive nights in a randomized crossover trial (4-wk washout). Ambulatory sleep measures included the Pittsburgh Insomnia Rating Scale (PIRS) completed at the end of each intervention period, and daily post-sleep questionnaire and wrist-actigraphy. PIRS total scores, and Quality of Life, Distress, and Sleep Parameter subscales, were improved in amber vs. clear lenses condition (p-values <0.05). Reported wake-time was significantly delayed, and mean subjective total sleep time (TST), overall quality, and soundness of sleep were significantly higher (p-values <0.05) in amber vs. clear lenses condition over the 7-d intervention period. Actigraphic measures of TST only were significantly higher in amber vs. clear lenses condition (p = 0.035). Wearing amber vs. clear lenses for 2-h preceding bedtime for 1 week improved sleep in individuals with insomnia symptoms. These findings have health relevance given the broad use of light-emitting devices before bedtime and prevalence of insomnia. Amber lenses represent a safe, affordable, and easily implemented therapeutic intervention for insomnia symptoms.
CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT02698800.

PMID: 29101797 [PubMed - as supplied by publisher]

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Calpain-1 regulates platelet function in a humanized mouse model of sickle cell disease.

Calpain-1 regulates platelet function in a humanized mouse model of sickle cell disease.

Thromb Res. 2017 Oct 26;160:58-65

Authors: Nwankwo JO, Gremmel T, Gerrits AJ, Mithila FJ, Warburton RR, Hill NS, Lu Y, Richey LJ, Jakubowski JA, Frelinger AL, Chishti AH

Abstract
One of the major contributors to sickle cell disease (SCD) pathobiology is the hemolysis of sickle red blood cells (RBCs), which release free hemoglobin and platelet agonists including adenosine 5'-diphosphate (ADP) into the plasma. While platelet activation/aggregation may promote tissue ischemia and pulmonary hypertension in SCD, modulation of sickle platelet dysfunction remains poorly understood. Calpain-1, a ubiquitous calcium-activated cysteine protease expressed in the hematopoietic cells, mediates aggregation of platelets in healthy mice. We generated calpain-1 knockout Townes sickle (SSCKO) mice to investigate the role of calpain-1 in the steady state and hypoxia/reoxygenation (H/R)-induced sickle platelet activation and aggregation, clot retraction, and pulmonary arterial hypertension. Using multi-electrode aggregometry, which measures platelet adhesion and aggregation in whole blood, we determined that steady state SSCKO mice exhibit significantly impaired PAR4-TRAP-stimulated platelet aggregation as compared to Townes sickle (SS) and humanized control (AA) mice. Interestingly, the H/R injury induced platelet hyperactivity in SS and SSCKO, but not AA mice, partially rescued the aggregation defect in SSCKO mice. The PAR4-TRAP-stimulated GPIIb-IIIa/αIIbβ3 integrin activation was normal in SSCKO platelets suggesting that an alternate mechanism mediates the impaired platelet aggregation in steady state SSCKO mice. Taken together, we provide the first evidence that calpain-1 regulates platelet hyperactivity in sickle mice, and may offer a viable pharmacological target to reduce platelet hyperactivity in SCD.

PMID: 29101791 [PubMed - as supplied by publisher]

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Sexual Dysfunction in Premenopausal Women With Obstructive Sleep Apnea.

Sexual Dysfunction in Premenopausal Women With Obstructive Sleep Apnea.

Urol J. 2017 Nov 04;14(6):5051-5056

Authors: Yilmaz Z, Sirinocak PB, Voyvoda B, Ozcan L

Abstract
PURPOSE: Sexual functions in the males with obstructive sleep apnea syndrome (OSAS) have been well investigated in the literature; however sexual functions in the premenopausal women with OSAS have been studied to a lesser extent.
MATERIALS AND METHODS: The study included 22 premenopausal women diagnosed as OSAS by the polysomnographic (PSG) evaluation. The control group included 13 premenopausal women suspected of sleep-relatedrespiratory disorder, but whose PSG tests were determined to be normal. Both groups were administered Epworth Sleep Scale (ESS), Beck Depression Scale (BDS), and Female Sexual Function Index (FSFI) questionnaire forms. Relations between disease parameters, and the total FSFI score, and scores of the six FSFI parameter were analyzed.
RESULTS: The total FSFI score in the cases with OSAS, was determined to be significantly lower than that of the control subjects (P = .031). Scores of the desire, arousal, and orgasm were determined to be significantly lower inthe patient group, compared to control group (P = .034; P = .048; P = .039). The total FSFI scores, and scores of the desire, arousal, lubrication, orgasm, satisfaction and pain subscales in the cases did not correlate significantly with the apnea-hypopnea index (AHI), Non-Rapid Eye Movement 1 (NREM1)%, NREM2%, NREM3%, REM%, the time spent with saturation O2< 90%, minimum oxygen saturation (%), ESS scores, and BDS scores (all P > .05).
CONCLUSION: Women with OSAS experience sexual dysfunction when compared with normal population. Clinical evaluation has to include also the evaluation of sexual life in women.

PMID: 29101760 [PubMed - in process]

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Numerical study of dynamic glottis and tidal breathing on respiratory sounds in a human upper airway model.

Numerical study of dynamic glottis and tidal breathing on respiratory sounds in a human upper airway model.

Sleep Breath. 2017 Nov 03;:

Authors: Xi J, Wang Z, Talaat K, Glide-Hurst C, Dong H

Abstract
BACKGROUND: Human snores are caused by vibrating anatomical structures in the upper airway. The glottis is a highly variable structure and a critical organ regulating inhaled flows. However, the effects of the glottis motion on airflow and breathing sound are not well understood, while static glottises have been implemented in most previous in silico studies. The objective of this study is to develop a computational acoustic model of human airways with a dynamic glottis and quantify the effects of glottis motion and tidal breathing on airflow and sound generation.
METHODS: Large eddy simulation and FW-H models were adopted to compute airflows and respiratory sounds in an image-based mouth-lung model. User-defined functions were developed that governed the glottis kinematics. Varying breathing scenarios (static vs. dynamic glottis; constant vs. sinusoidal inhalations) were simulated to understand the effects of glottis motion and inhalation pattern on sound generation. Pressure distributions were measured in airway casts with different glottal openings for model validation purpose.
RESULTS: Significant flow fluctuations were predicted in the upper airways at peak inhalation rates or during glottal constriction. The inhalation speed through the glottis was the predominating factor in the sound generation while the transient effects were less important. For all frequencies considered (20-2500 Hz), the static glottis substantially underestimated the intensity of the generated sounds, which was most pronounced in the range of 100-500 Hz. Adopting an equivalent steady flow rather than a tidal breathing further underestimated the sound intensity. An increase of 25 dB in average was observed for the life condition (sine-dynamic) compared to the idealized condition (constant-rigid) for the broadband frequencies, with the largest increase of approximately 40 dB at the frequency around 250 Hz.
CONCLUSION: Results show that a severely narrowing glottis during inhalation, as well as flow fluctuations in the downstream trachea, can generate audible sound levels.

PMID: 29101633 [PubMed - as supplied by publisher]

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Sensory coding accuracy and perceptual performance are improved during the desynchronized cortical state.

Sensory coding accuracy and perceptual performance are improved during the desynchronized cortical state.

Nat Commun. 2017 Nov 03;8(1):1308

Authors: Beaman CB, Eagleman SL, Dragoi V

Abstract
Cortical activity changes continuously during the course of the day. At a global scale, population activity varies between the 'synchronized' state during sleep and 'desynchronized' state during waking. However, whether local fluctuations in population synchrony during wakefulness modulate the accuracy of sensory encoding and behavioral performance is poorly understood. Here, we show that populations of cells in monkey visual cortex exhibit rapid fluctuations in synchrony ranging from desynchronized responses, indicative of high alertness, to highly synchronized responses. These fluctuations are local and control the trial variability in population coding accuracy and behavioral performance in a discrimination task. When local population activity is desynchronized, the correlated variability between neurons is reduced, and network and behavioral performance are enhanced. These findings demonstrate that the structure of variability in local cortical populations is not noise but rather controls how sensory information is optimally integrated with ongoing processes to guide network coding and behavior.

PMID: 29101393 [PubMed - in process]

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T cells upon activation promote endothelin 1 production in monocytes via IFN-γ and TNF-α.

T cells upon activation promote endothelin 1 production in monocytes via IFN-γ and TNF-α.

Sci Rep. 2017 Nov 03;7(1):14500

Authors: Shinagawa S, Okazaki T, Ikeda M, Yudoh K, Kisanuki YY, Yanagisawa M, Kawahata K, Ozaki S

Abstract
Endothelin 1 (ET-1), mainly produced from vascular endothelial cells, induces vasoconstriction in physiological conditions. The endothelin receptor antagonist is among the most effective agents for pulmonary hypertension. However, little is known about the production source of ET-1 in inflammation and immunity. Here, we studied whether T cell-mediated ET-1 production system exists and operates independent of the production system in vascular endothelial cells. ET-1 production was readily detectable in the culture supernatant of human PBMCs and murine spleen cells stimulated with anti-CD3 antibody. Immunocytostaining showed that ET-1-producing cells emerged only in PBMCs stimulated with anti-CD3 antibody. Using the Transwell system, both murine and human monocytes sorted with magnetic beads in the inner chamber produced ET-1 when T cells were activated with antigen or anti-CD3 antibody in the outer chamber. This ET-1 production was inhibited by anti-IFN-γ and/or TNF-α antibody. Furthermore, monocytes purified from ET(flox/flox);Tie2-Cre( + ) mice, which conditionally lack ET-1 in hematopoietic stem cells and vascular endothelial cells, did not produce ET-1 even when stimulated by antigen-specific T cell activation. This study demonstrates the existence of an immune-mediated ET-1 production induced by T cells upon activation through IFN-γ and TNF-α.

PMID: 29101349 [PubMed - in process]

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Development and Validation of a Multi-Algorithm Analytic Platform to Detect Off-Target Mechanical Ventilation.

Development and Validation of a Multi-Algorithm Analytic Platform to Detect Off-Target Mechanical Ventilation.

Sci Rep. 2017 Nov 03;7(1):14980

Authors: Adams JY, Lieng MK, Kuhn BT, Rehm GB, Guo EC, Taylor SL, Delplanque JP, Anderson NR

Abstract
Healthcare-specific analytic software is needed to process the large volumes of streaming physiologic waveform data increasingly available from life support devices such as mechanical ventilators. Detection of clinically relevant events from these data streams will advance understanding of critical illness, enable real-time clinical decision support, and improve both clinical outcomes and patient experience. We used mechanical ventilation waveform data (VWD) as a use case to address broader issues of data access and analysis including discrimination between true events and waveform artifacts. We developed an open source data acquisition platform to acquire VWD, and a modular, multi-algorithm analytic platform (ventMAP) to enable automated detection of off-target ventilation (OTV) delivery in critically-ill patients. We tested the hypothesis that use of artifact correction logic would improve the specificity of clinical event detection without compromising sensitivity. We showed that ventMAP could accurately detect harmful forms of OTV including excessive tidal volumes and common forms of patient-ventilator asynchrony, and that artifact correction significantly improved the specificity of event detection without decreasing sensitivity. Our multi-disciplinary approach has enabled automated analysis of high-volume streaming patient waveform data for clinical and translational research, and will advance the study and management of critically ill patients requiring mechanical ventilation.

PMID: 29101346 [PubMed - in process]

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Dynamic coupling between slow waves and sleep spindles during slow wave sleep in humans is modulated by functional pre-sleep activation.

Dynamic coupling between slow waves and sleep spindles during slow wave sleep in humans is modulated by functional pre-sleep activation.

Sci Rep. 2017 Nov 03;7(1):14496

Authors: Yordanova J, Kirov R, Verleger R, Kolev V

Abstract
Co-existent sleep spindles and slow waves have been viewed as a mechanism for offline information processing. Here we explored if the temporal synchronization between slow waves and spindle activity during slow wave sleep (SWS) in humans was modulated by preceding functional activations during pre-sleep learning. We activated differentially the left and right hemisphere before sleep by using a lateralized variant of serial response time task (SRTT) and verified these inter-hemispheric differences by analysing alpha and beta electroencephalographic (EEG) activities during learning. The stability and timing of coupling between positive and negative phases of slow waves and sleep spindle activity during SWS were quantified. Spindle activity was temporally synchronized with both positive (up-state) and negative (down-state) slow half waves. Synchronization of only the fast spindle activity was laterally asymmetric after learning, corresponding to hemisphere-specific activations before sleep. However, the down state was associated with decoupling, whereas the up-state was associated with increased coupling of fast spindle activity over the pre-activated hemisphere. These observations provide original evidence that (1) the temporal grouping of fast spindles by slow waves is a dynamic property of human SWS modulated by functional pre-sleep activation patterns, and (2) fast spindles synchronized by slow waves are functionally distinct.

PMID: 29101344 [PubMed - in process]

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In human non-REM sleep, more slow-wave activity leads to less blood flow in the prefrontal cortex.

In human non-REM sleep, more slow-wave activity leads to less blood flow in the prefrontal cortex.

Sci Rep. 2017 Nov 03;7(1):14993

Authors: Tüshaus L, Omlin X, Tuura RO, Federspiel A, Luechinger R, Staempfli P, Koenig T, Achermann P

Abstract
Cerebral blood flow (CBF) is related to integrated neuronal activity of the brain whereas EEG provides a more direct measurement of transient neuronal activity. Therefore, we addressed what happens in the brain during sleep, combining CBF and EEG recordings. The dynamic relationship of CBF with slow-wave activity (SWA; EEG sleep intensity marker) corroborated vigilance state specific (i.e., wake, non-rapid eye movement (NREM) sleep stages N1-N3, wake after sleep) differences of CBF e.g. in the posterior cingulate, basal ganglia, and thalamus, indicating their role in sleep-wake regulation and/or sleep processes. These newly observed dynamic correlations of CBF with SWA - namely a temporal relationship during continuous NREM sleep in individuals - additionally implicate an impact of sleep intensity on the brain's metabolism. Furthermore, we propose that some of the aforementioned brain areas that also have been shown to be affected in disorders of consciousness might therefore contribute to the emergence of consciousness.

PMID: 29101338 [PubMed - in process]

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Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: More Work to Be Done.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: More Work to Be Done.

Circ Cardiovasc Qual Outcomes. 2017 Nov;10(11):

Authors: Auger WR, Kim NH

PMID: 29101269 [PubMed - in process]

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The "glymphatic" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation?

The "glymphatic" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation?

FASEB J. 2017 Nov 03;:

Authors: Smith AJ, Verkman AS

Abstract
How solutes and macromolecules are removed from brain tissue is of central importance in normal brain physiology and in how toxic protein aggregates are cleared in neurodegenerative conditions, including Alzheimer's disease (AD). Conventionally, solute transport in the narrow and tortuous extracellular space in brain parenchyma has been thought to be primarily diffusive and nondirectional. The recently proposed "glymphatic" (glial-lymphatic) hypothesis posits that solute clearance is convective and driven by active fluid transport from para-arterial to paravenous spaces though aquaporin-4 water channels in astrocyte endfeet. Glymphatic, convective solute clearance has received much attention because of its broad implications for AD and other brain pathologies and even the function of sleep. However, the theoretical plausibility of glymphatic transport has been questioned, and recent data have challenged its experimental underpinnings. A substantiated mechanism of solute clearance in the brain is of considerable importance because of its implications for pathogenic mechanisms of neurologic diseases and delivery of therapeutics.-Smith, A. J., Verkman, A. S. The "glymphatic" mechanism for solute clearance in Alzheimer's disease: game changer or unproven speculation?

PMID: 29101220 [PubMed - as supplied by publisher]

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Transcription factor ΔFosB acts within the nucleus of the solitary tract to increase mean arterial pressure during exposures to intermittent hypoxia.

Transcription factor ΔFosB acts within the nucleus of the solitary tract to increase mean arterial pressure during exposures to intermittent hypoxia.

Am J Physiol Heart Circ Physiol. 2017 Nov 03;:ajpheart.00268.2017

Authors: Wu Q, Cunningham JT, Mifflin SW

Abstract
ΔFosB is a member of the AP-1 family of transcription factors. ΔFosB has low constitutive expression in the central nervous system and is induced following exposure of rodents to intermittent hypoxia (IH), a model of the arterial hypoxemia that accompanies sleep apnea. We hypothesize ΔFosB in the nucleus of solitary tract (NTS) contributes to increased mean arterial pressure (MAP) during IH. The NTS of 11 male Sprague Dawley rats was injected (3 sites, 100nl per site) with a dominant-negative against ΔFosB (ΔJunD) in an adeno-associated viral vector (AAV)-green fluorescent protein (GFP) reporter. The NTS of 10 rats was injected with AAV-GFP as sham controls. Two weeks after NTS injections rats were exposed to IH for 8h/day, 7 days and MAP recorded using telemetry. In the sham group 7 days IH increased MAP from 99.8 ± 1.1 mmHg to 107.3 ± 0.5 mmHg in the day and from 104.4 ± 1.1 mmHg to 109.8 ± 0.6 in the night. In the group receiving ΔJunD, IH increased MAP during the day from 95.9 ± 1.7 mmHg to 101.3 ± 0.4 mmHg; during the dark MAP increased from 100.9 ± 1.7 mmHg to 102.8 ± 0.5 mmHg (both significantly lower than sham p<0.05). Following injection of the dominant-negative construct in the NTS, IH-induced ΔFosB immunoreactivity was decreased in paraventricular nucleus (p < 0.05), however no change was observed in rostral ventrolateral medulla. These data indicate that ΔFosB within the NTS contributes to the increase in MAP induced by IH exposure.

PMID: 29101166 [PubMed - as supplied by publisher]

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Development and Validation of a Taxonomy for Characterizing Measurements in Health Self-Quantification.

Development and Validation of a Taxonomy for Characterizing Measurements in Health Self-Quantification.

J Med Internet Res. 2017 Nov 03;19(11):e378

Authors: Almalki M, Gray K, Martin-Sanchez F

Abstract
BACKGROUND: The use of wearable tools for health self-quantification (SQ) introduces new ways of thinking about one's body and about how to achieve desired health outcomes. Measurements from individuals, such as heart rate, respiratory volume, skin temperature, sleep, mood, blood pressure, food consumed, and quality of surrounding air can be acquired, quantified, and aggregated in a holistic way that has never been possible before. However, health SQ still lacks a formal common language or taxonomy for describing these kinds of measurements. Establishing such taxonomy is important because it would enable systematic investigations that are needed to advance in the use of wearable tools in health self-care. For a start, a taxonomy would help to improve the accuracy of database searching when doing systematic reviews and meta-analyses in this field. Overall, more systematic research would contribute to build evidence of sufficient quality to determine whether and how health SQ is a worthwhile health care paradigm.
OBJECTIVE: The aim of this study was to investigate a sample of SQ tools and services to build and test a taxonomy of measurements in health SQ, titled: the classification of data and activity in self-quantification systems (CDA-SQS).
METHODS: Eight health SQ tools and services were selected to be examined: Zeo Sleep Manager, Fitbit Ultra, Fitlinxx Actipressure, MoodPanda, iBGStar, Sensaris Senspod, 23andMe, and uBiome. An open coding analytical approach was used to find all the themes related to the research aim.
RESULTS: This study distinguished three types of measurements in health SQ: body structures and functions, body actions and activities, and around the body.
CONCLUSIONS: The CDA-SQS classification should be applicable to align health SQ measurement data from people with many different health objectives, health states, and health conditions. CDA-SQS is a critical contribution to a much more consistent way of studying health SQ.

PMID: 29101092 [PubMed - in process]

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The limbic and neocortical contribution of α-synuclein, tau, and β-amyloid to disease duration in dementia with Lewy bodies.

The limbic and neocortical contribution of α-synuclein, tau, and β-amyloid to disease duration in dementia with Lewy bodies.

Alzheimers Dement. 2017 Oct 31;:

Authors: Ferman TJ, Aoki N, Crook JE, Murray ME, Graff-Radford NR, van Gerpen JA, Uitti RJ, Wszolek ZK, Graff-Radford J, Pedraza O, Kantarci K, Boeve BF, Dickson DW

Abstract
INTRODUCTION: We sought to assess the individual and combined contribution of limbic and neocortical α-synuclein, tau, and β-amyloid to duration of illness in dementia with Lewy bodies (DLB).
METHODS: Quantitative digital pathology of neocortical and limbic α-synuclein, tau, and β-amyloid was assessed in 49 patients with clinically probable DLB. Regression modeling examined the unique and shared contribution of each pathology to the variance of illness duration.
RESULTS: Patients with diffuse Lewy body disease had more severe pathology of each type and a shorter duration of illness than individuals with transitional Lewy body disease. The three pathologies accounted for 25% of the total variance of duration of illness, with 19% accounted for by α-synuclein alone or in combination with tau and β-amyloid. When the diffuse Lewy body disease group was examined separately, α-synuclein deposition significantly exceeded that of tau and β-amyloid. In this model, 20% of 24% total variance in the model for duration of illness was accounted for independently by α-synuclein.
DISCUSSION: In DLB, α-synuclein is an important predictor of disease duration, both independently and synergistically with tau and β-amyloid.

PMID: 29100980 [PubMed - as supplied by publisher]

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A Phase II Clinical Trial of Low Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis.

A Phase II Clinical Trial of Low Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis.

Chest. 2017 Oct 31;:

Authors: Rosas IO, Goldberg HJ, Collard HR, El-Chemaly S, Flaherty K, Hunninghake GM, Lasky JA, Lederer DJ, Machado R, Martinez FJ, Maurer R, Teller D, Noth I, Peters E, Raghu G, Garcia JGN, Choi AMK

Abstract
BACKGROUND: Pre-clinical studies have demonstrated that low-dose carbon monoxide (CO) can abrogate experimental lung fibrosis. To test the therapeutic role of inhaled CO, we designed a clinical study in patients with idiopathic pulmonary fibrosis (IPF).
METHODS: We conducted a multicenter, phase IIa, double-blinded, sham-controlled, clinical trial. IPF patients were randomized to treatment with inhaled CO at 100 - 200 parts per million (ppm) or to inhaled 21% oxygen for 2 hours daily, twice weekly, for 12 weeks. The primary study endpoint was the difference in change in metalloproteinase-7 (MMP7) serum concentration following 12 weeks of treatment. Secondary endpoints included pulmonary function test measures, six-minute walk distance, rates of adverse events, acute exacerbation, hospitalization and death and quality of life measures.
FINDINGS: Fifty-eight subjects were randomized to treatment with inhaled CO (n = 29) or placebo (n = 29). Despite modest increases in CO blood levels, the change in MMP7 concentrations following 12-weeks of treatment did not significantly differ between the study arms (MMP7 difference at week 12 was -0.90 ng/ml, 95% CI -4.18 to 2.38 ng/ml). No differences were observed in physiologic measures, incidence of acute exacerbations, hospitalization, death or patient-reported outcomes. Importantly no differences in distribution of adverse events were noted between the treatment arms.
INTERPRETATION: Inhaled CO is well tolerated and can be safely administered to IPF patients in the ambulatory setting; however inhaled CO did not result in significant changes in study endpoints. Our findings support testing the efficacy of inhaled therapies in future IPF clinical trials.
FUNDING: NHLBI Grant HL105371.

PMID: 29100885 [PubMed - as supplied by publisher]

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Highly relevant stimuli may passively elicit processes associated with consciousness during the sleep onset period.

Highly relevant stimuli may passively elicit processes associated with consciousness during the sleep onset period.

Conscious Cogn. 2017 Oct 31;:

Authors: Tavakoli P, Varma S, Campbell K

Abstract
Sleep onset marks the transition from waking to sleep, during which conscious awareness of the external environmental is gradually lost. The present study examines the extent of processing of acoustic change during sleep onset. An auditory optimal paradigm was used to record event-related potentials to six deviant stimuli during wakefulness, stage N1, and stage N2 sleep. During waking and early-stage N1, two of the deviants, environmental sounds and white noise, elicited a P3a reflecting processes that may lead to conscious awareness of acoustic change. Surprisingly, the P3a was also observed following both deviants during late-stage N1, a period thought to represent decreased awareness of the environment. Only the environmental sounds continued to elicit a P3a during stage N2 sleep, associated with the loss of consciousness of the external environment. Certain auditory stimuli may thus continue to activate processes that may lead to conscious awareness during the sleep onset period.

PMID: 29100795 [PubMed - as supplied by publisher]

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Psychometric Properties of Voice Activity Participation Profile-Persian Version (VAPPP).

Psychometric Properties of Voice Activity Participation Profile-Persian Version (VAPPP).

J Voice. 2017 Oct 31;:

Authors: Faham M, Anaraki ZG, Ahmadi A, Ebadi A, Silverman EP

Abstract
OBJECTIVES: Individuals with voice disorders may experience limits in activity and restricted participation in daily activities. The aim of this study was to investigate the psychometric properties of the Voice Activity Participation Profile-Persian Version (VAPPP), a questionnaire which specifically investigates activity limitation and participation restriction in Persian-speaking individuals with voice disorders.
METHOD: We completed a translation procedure according to World Health Organization guidelines, prior to administering the questionnaire to 208 participants (156 patients with dysphonia and 52 controls), each of whom completed the questionnaire. We examined various psychometric properties including item analysis, factor analysis, internal consistency, discriminant validity, criterion-related validity, and test-retest reliability were investigated for this questionnaire.
RESULTS: Confirmatory factor analysis revealed that the 27 items on the VAPPP were distributed across four factors and that the first question, which assesses self-perceived dysphonia severity, was grouped separately. All the four subscales and total VAPPP have high internal consistency and test-retest reliability based on Cronbach's alpha coefficients and the intraclass correlation coefficient (ICC). Job effects (α = 0.85; ICC = 0.96), daily communication effects (α = 0.96; ICC = 0.83), social communication effects (α = 0.91; ICC = 0.93), emotional effects (α = 0.94; ICC = 0.76), and total score (α = 0.97; ICC = 0.88) are presented. VAPPP scores in patients with dysphonia were significantly different from those of the healthy control group (P < 0.001). The VAPPP total score has a high correlation to the Voice Handicap Index (r = 0.86; P < 0.001) CONCLUSION: The VAPPP is a reliable and valid tool for evaluating the quality of life of patients with dysphonia in Iran.

PMID: 29100714 [PubMed - as supplied by publisher]

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Relationship between frequency spectrum of heart rate variability and autonomic nervous activities during sleep in newborns.

Relationship between frequency spectrum of heart rate variability and autonomic nervous activities during sleep in newborns.

Brain Dev. 2017 Oct 31;:

Authors: Takatani T, Takahashi Y, Yoshida R, Imai R, Uchiike T, Yamazaki M, Shima M, Nishikubo T, Ikada Y, Fujimoto S

Abstract
INTRODUCTION: We analyzed the frequency spectrum of two neonatal sleep stages, namely active sleep and quiet sleep, and the relationship between these sleep stages and autonomic nervous activity in 74 newborns and 16 adults as a comparison.
METHOD: Active and quiet sleep were differentiated by electroencephalogram (EEG) patterns, eye movements, and respiratory wave patterns; autonomic activity was analyzed using the RR interval of simultaneously recorded electrocardiogram (ECG) signals. Power values (LFa, absolute low frequency; HFa, absolute high frequency), LFa/HFa ratio, and the values of LFn (normalized low frequency) and HFn (normalized high frequency) were obtained. Synchronicity between the power value of HFa and the LFa/HFa ratio during active and quiet sleep was also examined by a new method of chronological demonstration of the power values of HFa and LFa/HFa.
RESULTS: We found that LFa, HFa and the LFa/HFa ratio during active sleep were significantly higher than those during quiet sleep in newborns; in adults, on the other hand, the LFa/HFa ratio during rapid eye movement (REM) sleep, considered as active sleep, was significantly higher than that during non-REM sleep, considered as quiet sleep, and HFa values during REM sleep were significantly lower than those during non-REM sleep. LFn during quiet sleep in newborns was significantly lower than that during active sleep. Conversely, HFn during quiet sleep was significantly higher than that during active sleep. Analysis of the four classes of gestational age groups at birth indicated that autonomic nervous activity in a few preterm newborns did not reach the level seen in full-term newborns. Furthermore, the power value of HFa and the LFa/HFa ratio exhibited reverse synchronicity.
CONCLUSION: These results indicate that the autonomic patterns in active and quiet sleep of newborns are different from those in REM and non-REM sleep of adults and may be develop to the autonomic patterns in adults, and that parasympathetic activity is dominant during quiet sleep as compared to active sleep from the results of LFn and HFn in newborns. In addition, in some preterm infants, delayed development of the autonomic nervous system can be determined by classifying the autonomic nervous activity pattern of sleep stages.

PMID: 29100617 [PubMed - as supplied by publisher]

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IJMS, Vol. 18, Pages 2337: View Point: Semaphorin-3E: An Emerging Modulator of Natural Killer Cell Functions?

IJMS, Vol. 18, Pages 2337: View Point: Semaphorin-3E: An Emerging Modulator of Natural Killer Cell Functions?

International Journal of Molecular Sciences doi: 10.3390/ijms18112337

Authors: Abdulaziz Alamri Abdelilah Soussi Gounni Sam Kung

Semaphorin-3E (Sema-3E) is a member of a large family of proteins originally identified as axon guidance cues in neural development. It is expressed in different cell types, such as immune cells, cancer cells, neural cells, and epithelial cells. Subsequently, dys-regulation of Sema-3E expression has been reported in various biological processes that range from cancers to autoimmune and allergic diseases. Recent work in our laboratories revealed a critical immunoregulatory role of Sema-3E in experimental allergic asthma. We further speculate possible immune modulatory function(s) of Sema-3E on natural killer (NK) cells.

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Sufficient Condition for Strongly Starlikeness of Normalized Mittag-Leffler Function

In the present investigation a sufficient condition is obtained for normalized Mittag-Leffler function to be starlike and strongly starlike in the open unit disk. Results obtained are new and their usefulness is depicted by deducing several interesting corollaries and examples.

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Classification of Region of Interest in Mammograms Using Dual Contourlet Transform and Improved KNN

Goal. Breast cancer is becoming one of the most common cancers among women. Early detection can help increase the survival rates. Feature extraction directly affects diagnosis result. In this work, a novel feature extraction method based on Dual Contourlet Transform (Dual-CT) is presented, and improved nearest neighbor (KNN) is employed to improve the classification performance. Method. This presented method includes three main sections: firstly, the Region of Interest (ROI) is cropped manually according to gold standard from Mammographic Image Analysis Society (MIAS) database; secondly, the ROIs are decomposed into different resolution levels using Dual-CT, contourlet, and wavelet; a set of texture features are extracted. Then improved KNN and traditional KNN are implemented for classification. Experiments are performed on 324 ROIs which include 206 normal cases and 118 abnormal cases; the abnormal cases are composed of 66 benign cases and 52 malignant cases. Results. Experimental results prove the validity and superiority of Dual-CT-based feature and improved KNN. In particular, 94.14% and 95.76% classification accuracy is achieved based on Dual-CT domain. Moreover, the proposed method is comparable with state-of-the-art methods in terms of accuracy. Contribution. Dual-CT-based feature is used for analyzing mammogram and can help improve breast cancer diagnosis accuracy.

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Corrigendum to “Effect of Naphthalene Acetic Acid on the Adventitious Rooting in Shoot Cuttings of Andrographis paniculata (Burm.f.) Wall. ex Nees: An Important Therapeutical Herb”

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Corrigendum to “Derivation of Diagonally Implicit Block Backward Differentiation Formulas for Solving Stiff Initial Value Problems”

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Quantitative Comparison of the Efficiency and Scalability of the Current and Future LTE Network Architectures

The core architecture of current mobile networks does not scale well to cope with future traffic demands owing to its highly centralized composition. Typically, it is believed that decentralization of the network architecture would be a sustainable approach to deal with ever growing amount of mobile data traffic. Nevertheless, the decentralization strategy of network architecture has not been properly examined through quantitative performance studies. Given that LTE will be the leading mobile networking technology in the coming 5–10 years, we conduct a hybrid study model to compare performance of current and future (decentralized) LTE network architectures. Particularly, our analysis presents numerical results quantifying impact of the number of attached nodes on the load at network routers and links, on the latency, and on the processing cost of the user’s data and control planes. Analytical results demonstrate that decentralization of the LTE network architecture achieves higher performance compared to the current architecture and improves the latency and cost of data packet delivery more than 10 and 6 times, respectively. Furthermore, it is also observed that GTP outperforms PMIP for all studied performance metrics in the decentralized architecture and provides about twofold better latency and cost for data packet delivery and roughly 6 times lower data traffic load on the network routers.

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Antidiarrheal Activity of Dissotis multiflora (Sm) Triana (Melastomataceae) Leaf Extract in Wistar Rats and Subacute Toxicity Evaluation

The present work was undertaken to evaluate antidiarrheal activity of ethanolic leaf extract of Dissotis multiflora (Sm) Triana (D. multiflora) on Shigella flexneri-induced diarrhea in Wistar rats and its subacute toxicity. Diarrhea was induced by oral administration of 1.2 × 109 cells/mL S. flexneri to rats. Antidiarrheal activity was investigated in rats with the doses of 111.42 mg/kg, 222.84 mg/kg, and 445.68 mg/kg. The level of biochemical parameters was assessed and organs histology examined by 14 days’ subacute toxicity. S. flexneri stool load decreased significantly in dose-dependent manner. The level of ALT increased () in male rats treated with the dose of 445.68 mg/kg while creatinine level increased in rats treated with both doses. In female rats, a significant decrease () of the level of AST and creatinine was noted in rats treated with the dose of 222.84 mg/kg of D. multiflora. Histological exams of kidney and liver of treated rats showed architectural modifications at the dose of 445.68 mg/kg. This finding suggests that D. multiflora leaf extract is efficient against diarrhea caused by S. flexneri but the treatment with doses lower than 222.84 mg/kg is recommended while further study is required to define the exact efficient nontoxic dose.

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A Concise Review on the Use of Mesenchymal Stem Cells in Cell Sheet-Based Tissue Engineering with Special Emphasis on Bone Tissue Regeneration

The integration of stem cell technology and cell sheet engineering improved the potential use of cell sheet products in regenerative medicine. This review will discuss the use of mesenchymal stem cells (MSCs) in cell sheet-based tissue engineering. Besides their adhesiveness to plastic surfaces and their extensive differentiation potential in vitro, MSCs are easily accessible, expandable in vitro with acceptable genomic stability, and few ethical issues. With all these advantages, they are extremely well suited for cell sheet-based tissue engineering. This review will focus on the use of MSC sheets in osteogenic tissue engineering. Potential application techniques with or without scaffolds and/or grafts will be discussed. Finally, the importance of osteogenic induction of these MSC sheets in orthopaedic applications will be demonstrated.

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A Heterogeneous System Based on Latent Semantic Analysis Using GPU and Multi-CPU

Latent Semantic Analysis (LSA) is a method that allows us to automatically index and retrieve information from a set of objects by reducing the term-by-document matrix using the Singular Value Decomposition (SVD) technique. However, LSA has a high computational cost for analyzing large amounts of information. The goals of this work are (i) to improve the execution time of semantic space construction, dimensionality reduction, and information retrieval stages of LSA based on heterogeneous systems and (ii) to evaluate the accuracy and recall of the information retrieval stage. We present a heterogeneous Latent Semantic Analysis (hLSA) system, which has been developed using General-Purpose computing on Graphics Processing Units (GPGPUs) architecture, which can solve large numeric problems faster through the thousands of concurrent threads on multiple CUDA cores of GPUs and multi-CPU architecture, which can solve large text problems faster through a multiprocessing environment. We execute the hLSA system with documents from the PubMed Central (PMC) database. The results of the experiments show that the acceleration reached by the hLSA system for large matrices with one hundred and fifty thousand million values is around eight times faster than the standard LSA version with an accuracy of 88% and a recall of 100%.

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On the Power of Simulation and Admissible Functions in Metric Fixed Point Theory

We investigate the existence and uniqueness of certain operators which form a new contractive condition via the combining of the notions of admissible function and simulation function contained in the context of complete -metric spaces. The given results not only unify but also generalize a number of existing results on the topic in the corresponding literature.

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An Adaptive Spectral Kurtosis Method Based on Optimal Filter

As a useful tool to detect protrusion buried in signals, kurtosis has a wide application in engineering, for example, in bearing fault diagnosis. Spectral kurtosis (SK) can further indicate the presence of a series of transients and their locations in the frequency domain. The factors influencing kurtosis values are first analyzed, leading to the conclusion that amplitude, not the frequency of signals, and noise make major contribution to kurtosis values. It is helpful to detect impulsive components if the components with big amplitude are removed from composite signals. Based on this cognition, an adaptive SK algorithm is proposed in this paper. The core steps of the proposed SK algorithm are to find maxima, add window around maxima, merge windows in the frequency domain, and then filter signals according to the merged window in the time domain. The parameters of the proposed SK algorithm are varying adaptively with signals. Some experimental results are presented to demonstrate the effectiveness of the proposed algorithm.

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Corrigendum to “On a Nonlinear Wave Equation Associated with Dirichlet Conditions: Solvability and Asymptotic Expansion of Solutions in Many Small Parameters”

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IJMS, Vol. 18, Pages 2336: Oxidative Stress in Cardiovascular Diseases: Involvement of Nrf2 Antioxidant Redox Signaling in Macrophage Foam Cells Formation

IJMS, Vol. 18, Pages 2336: Oxidative Stress in Cardiovascular Diseases: Involvement of Nrf2 Antioxidant Redox Signaling in Macrophage Foam Cells Formation

International Journal of Molecular Sciences doi: 10.3390/ijms18112336

Authors: Bee Ooi Bey Goh Wei Yap

Oxidative stress is an important risk factor contributing to the pathogenesis of cardiovascular diseases. Oxidative stress that results from excessive reactive oxygen species (ROS) production accounts for impaired endothelial function, a process which promotes atherosclerotic lesion or fatty streaks formation (foam cells). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor involved in cellular redox homeostasis. Upon exposure to oxidative stress, Nrf2 is dissociated from its inhibitor Keap-1 and translocated into the nucleus, where it results in the transcriptional activation of cell defense genes. Nrf2 has been demonstrated to be involved in the protection against foam cells formation by regulating the expression of antioxidant proteins (HO-1, Prxs, and GPx1), ATP-binding cassette (ABC) efflux transporters (ABCA1 and ABCG1) and scavenger receptors (scavenger receptor class B (CD36), scavenger receptor class A (SR-A) and lectin-type oxidized LDL receptor (LOX-1)). However, Nrf2 has also been reported to exhibit pro-atherogenic effects. A better understanding on the mechanism of Nrf2 in oxidative stress-induced cardiac injury, as well as the regulation of cholesterol uptake and efflux, are required before it can serve as a novel therapeutic target for cardiovascular diseases prevention and treatment.

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IJMS, Vol. 18, Pages 2338: Recipient HLA-G +3142 CC Genotype and Concentrations of Soluble HLA-G Impact on Occurrence of CMV Infection after Living-Donor Kidney Transplantation

IJMS, Vol. 18, Pages 2338: Recipient HLA-G +3142 CC Genotype and Concentrations of Soluble HLA-G Impact on Occurrence of CMV Infection after Living-Donor Kidney Transplantation

International Journal of Molecular Sciences doi: 10.3390/ijms18112338

Authors: Hana Guberina Rafael Tomoya Michita Sebastian Dolff Anja Bienholz Mirko Trilling Falko Heinemann Peter Horn Andreas Kribben Oliver Witzke Vera Rebmann

The expression modulation of the immunosuppressive non-classical Human leukocyte antigen-G (HLA-G) molecule and its soluble isoforms is an immune evasion strategy being deployed by cytomegalovirus (CMV). The +3142 C>G single nucleotide polymorphism (SNP) located within the 3′ untranslated region (3′UTR) is of crucial importance for the regulation of HLA-G expression. Therefore, we analyzed the influence of the +3142 C>G HLA-G SNP on the occurrence of CMV infection in a cohort of 178 living-donor kidney recipients and their 178 corresponding donors. In addition, soluble HLA-G (sHLA-G) levels were quantified before and after transplantation. The presence of the HLA-G +3142 CC genotype in recipients, but not donors of our cohort as along with elevated sHLA-G levels (≥ 6.1 ng/mL) were associated with higher susceptibility to CMV infection after transplantation. Our results provided evidence that i) HLA-G is implicated in the establishment of CMV after living-donor kidney transplantation and ii) recipient HLA-G +3142 CC genotype and sHLA-G concentration levels could represent important predictive risk markers for CMV infection.

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Cytomegalovirus reactivation in patients with refractory checkpoint inhibitor-induced colitis

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Cindy Franklin, Isabelle Rooms, Melanie Fiedler, Henning Reis, Laura Milsch, Saskia Herz, Elisabeth Livingstone, Lisa Zimmer, Kurt Werner Schmid, Ulf Dittmer, Dirk Schadendorf, Bastian Schilling
ObjectivesImmune checkpoint inhibitors can cause severe immune-related adverse events, with immune-related diarrhea and colitis (irColitis) being among the most frequent ones. While the majority of patients with irColitis respond well to corticosteroid treatment ± other immunomodulatory drugs such as infliximab, some patients do not show resolution of their symptoms. In the present study, we analysed the frequency of therapy-refractory irColitis, the underlying cause, and useful diagnostic approaches.MethodsBetween 2006 and 2016, 370 patients with metastatic malignant melanoma were treated with checkpoint inhibitors at the Department of Dermatology at the University Hospital Essen. All patients were identified for whom diarrhea and/or colitis was documented in the digital patient records. Patients who did not respond to standard immunosuppressive therapy within 2 weeks were classified as refractory. Demographic and clinical data of all patients were collected.ResultsWe identified 41 patients with irColitis, the majority occurring during treatment with ipilimumab. Amongst these, 5 (12.2%) were refractory to standard immunomodulatory treatment with corticosteroids and infliximab. Therapy-refractory cases tended to show more severe inflammation in colonic biopsies (p = 0.04). In all therapy-refractory cases cytomegalovirus (CMV) was detectable. CMV-DNA in colonic biopsies and in plasma was significantly more often detectable in therapy-refractory cases (in colonic biopsies p = 0.005, in plasma: p = 0.002). Presence of serum CMV IgM and positive immunohistochemical stainings of colon biopsies for CMV were also associated with refractory colitis (p=0.021; p = 0.053).ConclusionsThis report on CMV reactivation during management of checkpoint inhibitor-induced colitis emphasises the need for repetitive diagnostic measures in treatment-refractory irColitis.

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Recurrence dynamics of breast cancer according to baseline body mass index

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Elia Biganzoli, Christine Desmedt, Marco Fornili, Evandro de Azambuja, Nathalie Cornez, Fernand Ries, Marie-Thérèse Closon-Dejardin, Joseph Kerger, Christian Focan, Angelo Di Leo, Jean-Marie Nogaret, Christos Sotiriou, Martine Piccart, Romano Demicheli
BackgroundIn cancer follow-up, in addition to the evaluation of survival probabilities, there is a fundamental need of assessing recurrence dynamics for optimal disease management. Although the time-dependent effect of the oestrogen receptor (ER) status of the tumour has already been described, so far no factor has proven to disentangle the multi-peak behaviour observed for breast cancer recurrences. Here, we aimed at investigating whether adiposity at diagnosis, reflected by increased patient's body mass index (BMI), could be associated with breast cancer recurrence patterns over time after primary cancer therapy.MethodsWe retrieved BMI from 734 of 777 patients with node-positive breast cancer from a phase III randomised clinical trial, which compared different chemotherapy regimens and had a median follow-up of 15.4 years. Cumulative incidence estimation as well as piecewise exponential models were carried out to estimate the distant recurrence dynamics, in all patients, as well as in subgroups based on the ER status, with the ER-positive group being further split according to the menopausal status.ResultsIn patients with ER-negative breast cancer, time-dependent analyses revealed that the hazard of late relapses could mainly be attributed to the overweight and obese patients. Within the subgroup of premenopausal patients with ER-positive tumours, obesity was associated with an early high narrow peak of distant recurrences followed by another main peak after 5 years of follow-up. The risk for overweight patients was intermediate between obese and normal-weight patients. In the postmenopausal subgroup of patients with ER-positive tumours, the distant recurrence rate was significantly more elevated in the overweight patients compared to the other BMI categories, and a second late peak of recurrences was also observed for the obese patients.ConclusionThese results demonstrate that the patient's BMI at diagnosis is associated with cancer recurrence dynamics. Patient adiposity should therefore be central to the exploration of late adjuvant treatment modalities.

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The association between health-related quality-of-life scores and clinical outcomes in metastatic castration-resistant prostate cancer patients: Exploratory analyses of AFFIRM and PREVAIL studies

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Tomasz M. Beer, Kurt Miller, Bertrand Tombal, David Cella, De Phung, Stefan Holmstrom, Cristina Ivanescu, Konstantina Skaltsa, Shevani Naidoo
BackgroundOur exploratory analysis examined the association between health-related quality of life (HRQoL) (baseline and change over time) and clinical outcomes (overall survival [OS]/radiographic progression-free survival [rPFS]) in metastatic castration-resistant prostate cancer (mCRPC).MethodsHRQoL, OS and rPFS were assessed in phase III trials comparing enzalutamide with placebo in chemotherapy-naïve (PREVAIL; NCT01212991) or post-chemotherapy (AFFIRM; NCT00974311) mCRPC. HRQoL was assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P). Multivariate analyses evaluated the prognostic significance of baseline and time-dependent scores after adjusting for treatment and clinical/demographic variables. Hazard ratios (HRs) and 95% confidence intervals (CIs) represented the hazard of rPFS or OS per minimally important difference (MID) score change in HRQoL variables.ResultsIn baseline and time-dependent multivariate analyses, OS was independently associated with multiple HRQoL measures across both studies. In time-dependent analyses, a 10-point (upper bound of MID range) increase (improvement) in FACT-P total score was associated with reductions in mortality risk of 19% in AFFIRM (HR 0.81 [95% CI 0.78–0.84]) and 21% in PREVAIL (HR 0.79 [0.76–0.83]). For baseline analyses, a 10-point increase in FACT-P total score was associated with reductions in mortality risk of 12% (HR 0.88 [0.84–0.93]) and 10% (HR 0.90 [0.86–0.95]) in AFFIRM and PREVAIL, respectively. rPFS was associated with a subset of HRQoL domains in both studies.ConclusionSeveral baseline HRQoL domains were prognostic for rPFS and OS in patients with mCRPC, and this association was maintained during treatment, indicating that changes in HRQoL are informative for patients' expected survival.

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Is post-mastectomy radiation therapy contributive in pN0-1mi breast cancer patients? Results of a French multi-centric cohort

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Violaine Forissier, Agnès Tallet, Monique Cohen, Jean-Marc Classe, Fabien Reyal, Nicolas Chopin, Chafika Mazouni, Pierre Gimbergues, Emile Daraï, Pierre Emmanuel Colombo, Pierre Azuar, Eric Lambaudie, Gilles Houvenaeghel
AimTo assess the value of post-mastectomy radiation therapy (PMRT) to breast cancer (BC) patients with no or minimal lymph node (LN) involvement.Materials and methodsWe retrospectively analysed a French multi-centric cohort of 4283 patients treated by mastectomy and axillary dissection, with or without PMRT, between 1980 and 2013. Practices were analysed for three treatment periods (1980–1999, 2000–2005 and 2006–2013). The impact of PMRT on loco-regional recurrence (LRR), disease-free survival (DFS), BC-specific survival and overall survival was assessed in pN0-1mi patients using multivariate analyses (logistic regression and Cox model). It was subsequently assessed based on the number of clinicopathological recurrence-risk factors, generating a prognostic index (French-PMRT index), to isolate a pN0-1mi patients subgroup that might derive a benefit from PMRT. We tested the accuracy of the Cambridge-PMRT (c-PMRT) index to discriminate between patients with significantly different outcomes and the value of PMRT in each c-PMRT prognostic group.ResultsMore than half of the pN0-1mi patients of our cohort underwent PMRT, which almost significantly improved LRR-free survival and DFS. Matching pN0-1mi patients based on the number of clinicopathologic recurrence-risk factors identified a higher risk subpopulation (≥3 recurrence-risk factors), but PMRT did not improve patient outcomes. Although the c-PMRT index had the potential to predict patient outcomes, its use did not help in making the decision of whether or not to use PMRT.ConclusionWe failed to isolate a subgroup of early BC patients without LN involvement suitable for PMRT, despite studying a large cohort.

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Response rate as a potential surrogate for survival and efficacy in patients treated with novel immune checkpoint inhibitors: A meta-regression of randomised prospective studies

Publication date: November 2017
Source:European Journal of Cancer, Volume 86
Author(s): Giandomenico Roviello, Fabrice Andre, Sergio Venturini, Barbara Pistilli, Giuseppe Curigliano, Massimo Cristofanilli, Pietro Rosellini, Daniele Generali
IntroductionTo assess the role of the tumour response rate (RR) after immune checkpoint inhibitors–based therapy as a potential surrogate end-point of progression-free survival (PFS) and overall survival (OS) in patients with solid tumours, we performed a trial-based meta-regression of randomised studies comparing different immune checkpoint inhibitors–based treatments.MethodsThe systematic literature search included the electronic databases and the proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome.ResultsTwenty-four trials, for a total of 11,894 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for PFS or the log(HR) for OS on the log(OR) for RR demonstrated weak associations (R² = 0.47; 95% confidence interval [CI], 0.03–0.77; P = 0.001; and R² = 0.32; 95% CI, 0.02–0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials according to different type of disease and different mechanism of action of immune checkpoint inhibitors showed a very weak association of the RR with the OS for non–small cell lung cancer indicated and a modest association of the RR with the PFS for cytotoxic T lymphocyte–associated antigen 4 checkpoint inhibitors.ConclusionThe results of the trial-based meta-regression analysis indicated a weak correlation between RR and OS, supporting future investigations to assess the surrogacy of RR in the patient treated with immune checkpoint inhibitors.

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Weekly cabazitaxel plus prednisone is effective and less toxic for ‘unfit’ metastatic castration-resistant prostate cancer: Phase II Spanish Oncology Genitourinary Group (SOGUG) trial

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Miguel Ángel Climent, Begoña Pérez-Valderrama, Begoña Mellado, Eva María Fernández Parra, Ovidio Fernández Calvo, María Ochoa de Olza, Laura Muinelo Romay, Urbano Anido, Montserrat Domenech, Susana Hernando Polo, José Ángel Arranz Arija, Cristina Caballero, María José Juan Fita, Daniel Castellano
AimCabazitaxel (CBZ), a novel tubulin-binding taxane, improves overall survival in metastatic castration-resistant prostate cancer (mCRPC) that progresses during or after docetaxel treatment. We have designed a phase II study to evaluate the efficacy and safety of CBZ as a weekly schedule for ‘unfit’ mCRPC patients after docetaxel failure.MethodsIn this single arm phase II study. CBZ was weekly administered in 1-hour infusion on days 1, 8, 15 and 22, every 5 weeks at 10 mg/m² to eligible ‘unfit’ patients; oral prednisone (5 mg) was administered twice a day. Circulating tumour cells (CTCs) were also collected. New treatment scheme was considered effective if at least 65% of patients met a clinical benefit criteria based on prostate-specific antigen (PSA)-progression-free survival (PFS) values at week 12.ResultsSeventy patients (median age: 73.9 years) were enrolled; overall, 71.4% had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2; and 84%, 16% and 11% had bone, liver and lung metastases, respectively. Objective partial response or stable disease was achieved in 61% of patients, while PSA responses of ≥50% and ≥80% were observed in 34.8% and 10.6%, respectively. The median PSA-PFS was 4.8 months; and 68.6% of patients had no progression at week 12. The most frequent grade 3/4 toxicities were neutropenia (2.8%), leukopenia (5.7%) and thrombocytopaenia (9%); no cases of febrile neutropenia were reported. Early CTC response was significantly correlated with PSA-PFS.ConclusionsCBZ/prednisone administered weekly to ‘unfit’ mCRPC patients appears to be as effective as classical standard 3-week scheme (TROPIC study) but with significantly lower toxicities and better tolerance. Early CTC response appears to be valuable as an early end-point of therapeutic efficacy.

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Site of childhood cancer care in the Netherlands

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): A.M.J. Reedijk, M. van der Heiden-van der Loo, O. Visser, H.E. Karim-Kos, J.A. Lieverst, J.G. de Ridder-Sluiter, J.W.W. Coebergh, L.C. Kremer, R. Pieters
BackgroundDue to the complexity of diagnosis and treatment, care for children and young adolescents with cancer preferably occurs in specialised paediatric oncology centres with potentially better cure rates and minimal late effects. This study assessed where children with cancer in the Netherlands were treated since 2004.MethodsAll patients aged under 18 diagnosed with cancer between 2004 and 2013 were selected from the Netherlands Cancer Registry (NCR) and linked with the Dutch Childhood Oncology Group (DCOG) database. Associations between patient and tumour characteristics site of care were tested statistically with logistic regression analyses.ResultsThis population-based study of 6021 children diagnosed with cancer showed that 82% of them were treated in a paediatric oncology centre. Ninety-four percent of the patients under 10 years of age, 85% of the patients aged 10–14 and 48% of the patients aged 15–17 were treated in a paediatric oncology centre. All International Classification of Childhood Cancers (ICCC), 3rd edition, ICCC-3 categories, except embryonal tumours, were associated with a higher risk of treatment outside a paediatric oncology centre compared to leukaemia. Multivariable analyses by ICCC-3 category revealed that specific tumour types such as chronic myelogenous leukaemia (CML), embryonal carcinomas, bone tumours other type than osteosarcoma, non-rhabdomyosarcomas, thyroid carcinomas, melanomas and skin carcinomas as well as lower-staged tumours were associated with treatment outside a paediatric oncology centre.ConclusionThe site of childhood cancer care in the Netherlands depends on the age of the cancer patient, type of tumour and stage at diagnosis. Collaboration between paediatric oncology centre(s), other academic units is needed to ensure most up-to-date paediatric cancer care for childhood cancer patients at the short and long term.

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Πληροφορίες

Κυριακή 5 Νοεμβρίου 2017

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