Influence of core joints in sandwich composites under in-plane static and fatigue loads

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): Elias A. Toubia, Abraham Elmushyakhi
Most designers are unaware of the influence of core junction in lightweight sandwich structures under axial load. Quantifying this effect and its criticality on the life of the structure is still a challenging task. In this study, a novel testing methodology was used to characterize this effect. Scarf and butt core joints in foam core sandwich composites were subjected to axial static and fatigue loads (R=0.1 and R=−1). Under cyclic axial load, differential movement (through-the-thickness) between the foam and core joint was more significant than anticipated. Non-destructive evaluation techniques were used to locate the damage and assess the failure mechanisms. The root-cause-failure analysis showed that cracks were initiated in the facesheets for the butt-joint, and in the core for the scarf-joint samples, respectively. Consequently, at 80% residual strength, the butt-joint reduced the predicted fatigue life by 42% and 32% at low and high cycle fatigue, respectively. Residual tensile tests revealed the sizeable damage induced by the traditional butt-joint design. This research confirmed that despite the facesheets' primary in-plane load carrying mechanisms, core junction will substantially influence the axial fatigue life of the structure.

Graphical abstract

http://ift.tt/2r58iZZ

Compressive properties of functionally graded lattice structures manufactured by selective laser melting

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): Sing Ying Choy, Chen-Nan Sun, Kah Fai Leong, Jun Wei
Additive manufacturing provides great geometrical freedom for fabricating structures with complex or customized architecture. One of the applications benefiting from this technology is the fabrication of functionally graded materials with high degree of control of internal architecture which can be strategic application in advanced energy absorption. This study aims to explore the mechanical properties of functionally graded lattice structures fabricated by an additive manufacturing technique namely, selective laser melting (SLM), with Ti-6Al-4V as the building material. Both cubic lattice and honeycomb lattice structures with varied strut diameter and density were designed and manufactured, and their physical characteristics, deformation behavior and compressive properties were investigated. The collapse of structure always started from least dense layer to the denser layers. In contrast, samples with uniform density showed abrupt shear failure with diagonal cracking across the whole structure. The plateau stress and specific energy absorption of density graded samples were higher than for uniform density samples for three out of four designs by up to 67% and 72%, respectively. In addition, density graded lattices showed distinct energy absorption behavior with cumulative energy absorption increasing as a power of strain function while uniform density lattices showed a near-linear relationship.

Graphical abstract

http://ift.tt/2r4FG2O

Flexible design of cellular Al2TiO5 and Al2TiO5-Al2O3 composite monoliths by reactive firing

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): Eleonora Lalli, Nuno M.D. Vitorino, Carla A.M. Portugal, João G. Crespo, Cristiana Boi, Jorge R. Frade, Andrei V. Kovalevsky
Cellular Al2TiO5 and Al2TiO5 – Al2O3 composite ceramics were obtained by emulsification of liquid paraffin in aqueous suspensions of mixed TiO2+Al2O3 powders, with subsequent burnout of the organic phase and 2-step reactive firing at high temperatures. The reactants ratio and paraffin to suspension volume ratio were used as primary parameters to control the phase composition and relevant microstructural features, while firing conditions were also adjusted for greater flexibility in designing Al2TiO5-based cellular materials. Taguchi experimental planning was used to assess the relevant impacts of 2-step firing parameters on phase composition and porosity, characterized by detailed XRD/SEM/EDS studies. The results emphasized the positive effects of Al2O3 excess in Al2TiO5 – Al2O3 composite ceramics on stabilization of the Al2TiO5 phase and also for flexible design of cellular materials with controlled porosity and phase distributions. Analysis of correlation matrixes identified the 2-step firing parameters with greatest impact on the porosity and phase composition, and these trends were confirmed by multivariate linear regression. The observed trends indicated significant differences in reactivity and densification mechanisms between compositions with nominal Al2TiO5 stoichiometry and composite materials. These differences were most obvious for samples with significant residual fractions of unreacted titania.

Graphical abstract

http://ift.tt/2sNbj1Z

Switchable and pH responsive porous surfaces based on polypeptide-based block copolymers

Publication date: 5 October 2017
Source:Materials & Design, Volume 131
Author(s): A.S. de León, A. del Campo, J. Rodríguez-Hernández, A. Muñoz-Bonilla
In the current work, we prepared stimuli responsive porous films by the breath figure approach using polymer blends consisting of high molecular weight polystyrene (HPS) and an amphiphilic block copolymer based on a pH sensitive poly(l-glutamic acid) (PGA) polypeptide. Thus, due to the breath figure mechanism the pores were enriched in pH responsive negatively charged carboxylate groups able to immobilize cationic molecules at pH above the pKa of the PGA. As a proof of concept, Rhodamine 6G was attached through electrostatic interactions at basic pH inside the cavities as shown by fluorescence microscopy. The variation of the wettability and the reversible immobilization of Rhodamine 6G as a function of pH were investigated by contact angle and fluorescence measurements. Moreover, the kinetics of the adsorption process of Rhodamine 6G onto the prepared smart films was explored evidencing a pseudo-second order kinetic model while the maximum absorption capacity at equilibrium was found to be ~6.4nmolg⁻¹.

Graphical abstract

http://ift.tt/2r4ENaC

Editorial Board

Publication date: July 2017
Source:Critical Reviews in Oncology/Hematology, Volume 115





http://ift.tt/2sMHnTN

The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: Systematic review and meta-analysis

Publication date: Available online 9 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Ross D Dolan, Stephen T McSorley, Paul G Horgan, Barry Laird, Donald C McMillan
IntroductionCancer remains a leading cause of death worldwide. While a curative intent is the aim of any surgical treatment many patients either present with or go onto develop disseminated disease requiring systemic anti-cancer therapy with a palliative intent. Given their limited life expectancy appropriate allocation of treatment is vital. It is recognised that systemic chemoradiotherapy may shorten the quality/quantity of life in patients with advanced cancer. It is against this background that the present systematic review and meta-analysis of the prognostic value of markers of the systemic inflammatory response in patients with advanced cancer was conducted.MethodsAn extensive literature review using targeted medical subject headings was carried out in the MEDLINE, EMBASE, and CDSR databases until the end of 2016. Titles were examined for relevance and studies relating to duplicate datasets, that were not published in English and that did not have full text availability were excluded. Full texts of relevant articles were obtained and were then examined to identify any further relevant articles.ResultsThe majority of studies were retrospective. The systemic inflammatory response, as evidenced by a number of markers at clinical thresholds, was reported to have independent prognostic value, across tumour types and geographical locations. In particular, C-reactive protein (CRP, 63 studies), albumin (33 studies) the Glasgow Prognostic Score (GPS, 44 studies) and the Neutrophil Lymphocyte Ratio (NLR, 59 articles) were consistently validated across tumour types and geographical locations. There was considerable variation in the thresholds reported to have prognostic value when CRP and albumin were examined. There was less variation in the thresholds reported for NLR and still less for the GPS.DiscussionThe systemic inflammatory response, especially as evidenced by the GPS and NLR, has reliable prognostic value in patients with advanced cancer. Further prospective studies of their clinical utility in randomised clinical trials and in treatment allocation are warranted.



http://ift.tt/2sdrDft

Adiponectin: its role in obesity-associated colon and prostate cancers

Publication date: Available online 9 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Santoshi Muppala, Siva KP Konduru, Neha Merchant, Judy Ramsoondar, Carlos Karan Rampersad, Balney Rajitha, Vidya Mukund, Jyothsna Kancherla, Anthea Hammond, Tapan Kumar Barik, Mastan Mannarapu, Afroz Alam, Riyaz Basha, Pallavula Veera Bramhachari, Dheeraj Verma, Pinninti Santosh Sushma, Subasini Pattnaik, Ganji Purnachandra Nagaraju
Adipose tissue synthesizes many proteins and hormones collectively called adipokines, which are linked to a number of diseases, including cancer. Low levels of adiponectin are reported to be a risk factor for obesity-related cancers including colorectal and prostate cancers. Accordingly, obesity/lifestyle-related diseases, including certain cancers, may be treated by developing drugs that act specifically on adiponectin levels in circulation. Adiponectin may also serve as a clinical biomarker in obesity-related diseases. Adiponectin-based therapies are known to inhibit cancer advancement and thus may provide a therapeutic approach to delay cancer progression. Better understanding of the function of adiponectin is of great significance in the fight against cancer. This timely review is concentrated on the role of adiponectin and the impact of obesity on the development of cancers, especially colorectal and prostate cancers.



http://ift.tt/2rb5QVL

BIOMARKERS OF RESPONSE TO PD-1/PD-L1 INHIBITION

Publication date: Available online 6 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Saman Maleki Vareki, Carmen Garrigós, Ignacio Duran
Immunotherapy is a promising treatment strategy for cancer that has recently shown unprecedented survival benefits in selected patients. A number of immunomodulatory agents that target immune system checkpoints such as the cytotoxic T-lymphocyte antigen 4 (CTLA-4), the programmed death-1 (PD-1) or its ligand (PD-L1), have received regulatory approval for the treatment of multiple cancers including malignant melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic head and neck squamous cell carcinoma. Nevertheless, a substantial proportion of patients treated with checkpoint inhibitors have little or no benefit while these treatments are costly and might have associated toxicities. Hence, the establishment of valid predictors of treatment response has become a priority. This review summarizes the current evidence around biomarkers of response to PD-1/PD-L1 inhibition, considering features related to the tumor and to the host immune system.



http://ift.tt/2rVLInx

Sub-solid Nodule Detection Performance on Reduced-dose Computed Tomography with Iterative Reduction

Publication date: Available online 9 June 2017
Source:Academic Radiology
Author(s): Yukihiro Nagatani, Masashi Takahashi, Mitsuru Ikeda, Tsuneo Yamashiro, Hisanobu Koyama, Mitsuhiro Koyama, Hiroshi Moriya, Satoshi Noma, Noriyuki Tomiyama, Yoshiharu Ohno, Kiyoshi Murata, Sadayuki Murayama
Rationale and ObjectivesThis study aimed to compare sub-solid nodule detection performances (SSNDP) on chest computed tomography (CT) with Adaptive Iterative Dose Reduction using Three Dimensional Processing (AIDR 3D) between 7 mAs (0.21 mSv) and 42 mAs (1.28 mSv) in total and in subgroups classified by nodular size, characteristics, and location, and analyze the association of SSNDP with size-specific dose estimate (SSDE).Materials and MethodsAs part of the Area-detector Computed Tomography for the Investigation of Thoracic Diseases Study, a Japanese multicenter research project, 68 subjects underwent chest CT with 120 kV, 0.35 seconds per rotation, and three tube currents: 240 mA (84 mAs), 120 mA (42 mAs), and 20 mA (7 mAs). The research committee of the study project outlined and approved our study protocols. The institutional review board of each institution approved this study. Axial 2-mm-thick CT images were reconstructed using AIDR 3D. Standard reference was determined by CT images at 84 mAs. Four radiologists recorded SSN presence by continuously distributed rating on CT at 7 mAs and 42 mAs. Receiver operating characteristic analysis was used to evaluate SSNDP at both doses in total and in subgroups classified by nodular longest diameter (LD) (≥5 mm), characteristics(pure and part-solid), and locations (ventral, intermediate, or dorsal; central or peripheral; and upper, middle, or lower). Detection sensitivity was compared among five groups of SSNs classified based on particular SSDE to nodule on CT with AIDR 3D at 7 mAs.ResultsTwenty-two part-solid and 86 pure SSNs were identified. For larger SSNs (LD ≥ 5 mm) as well as subgroups classified by nodular locations and part-solid nodules, SSNDP was similar in both methods (area under the receiver operating characteristics curve: 0.96 ± 0.02 in CT at 7 mAs and 0.97 ± 0.01 in CT at 42 mAs), with acceptable interobserver agreements in five locations. For larger SSNs (LD ≥ 5 mm), on CT at 42 mAs, no significant differences in detection sensitivity were found among the five groups classified by SSDE, whereas on CT with 7 mAs, four groups with SSDE of 0.65 or higher were superior in detection sensitivity to the other group, with SSDE less than 0.65 mGy.ConclusionsFor SSNs with 5 mm or more in cases with normal range of body habitus, CT at 7 mAs was demonstrated to have comparable SSNDP to CT at 42 mAs regardless of nodular location and characteristics, and SSDE higher than 0.65 mGy is desirable to obtain sufficient SSNDP.



http://ift.tt/2rWpORr

Tailored Design of Multifunctional and Programmable pH-responsive Self-assembling Polypeptides as Drug Delivery Nanocarrier for Cancer Therapy

Publication date: Available online 9 June 2017
Source:Acta Biomaterialia
Author(s): Tzu-Wei Wang, Chia-Wei Yeh, Chen-Hsiang Kuan, Li-Wen Wang, Liang-Hsin Chen, Hsi-Chin Wu, Jui-Shen Sun
Breast cancer has become the second leading cause of cancer-related mortality in female wherein more than 90% of breast cancer-related death results from cancer metastasis to distant organs at advanced stage. The purpose of this study is to develop biodegradable nanoparticles composed of natural polypeptides and calcium phosphate (CaP) with sequential pH-responsivity to tumor microenvironments for active targeted drug delivery. Two different amphiphilic copolymers, poly(ethylene glycol)3400-aconityl linkage-poly(L-glutamic acid)15-poly(L-histidine)10-poly(L-leucine)10 and LyP1-poly(ethylene glycol)1100-poly(L-glutamic acid)15-poly(L-histidine)10-poly(L-leucine)10, were exploited to self-assemble into micelles in aqueous phase. The bio-stable nanoparticles provide three distinct functional domains: the anionic PGlu shell for CaP mineralization, the protonation of PHis segment for facilitating anticancer drug release at target site, and the hydrophobic core of PLeu for encapsulation of anticancer drugs. Furthermore, the hydrated PEG outer corona is used for prolonging circulation time, while the active targeting ligand, LyP-1, is served to bind to breast cancer cells and lymphatic endothelial cells in tumor for inhibiting metastasis. Mineralized DOX-loaded nanoparticles (M-DOX NPs) efficiently prevent the drug leakage at physiological pH value and facilitate the encapsulated drug release at acidic condition when compared to DOX-loaded nanoparticles (DOX NPs). M-DOX NPs with LyP-1 targeting ligand effectively accumulated in MDA-MB-231 breast cancer cells. The inhibition effect on cell proliferation also enhances with time, illustrating the prominent anti-tumor efficacy. Moreover, the in vitro metastatic inhibition model shows the profound inhibition effect of inhibitory nanoparticles. In brief, this self-assembling peptide-based drug delivery nanocarrier with multifunctionality and programmable pH-sensitivity is of great promise and potential for anti-cancer therapy.Statement of SignificanceThis tailored-design polypeptide-based nanoparticles with self-assembling and programmable stimulus-responsive properties enable to 1) be stable in physiological pH value with a low level of drug loss and effectively release the encapsulated drug with pH variations according to the tumor microenvironment, 2) enhanced targeting ability to hard-to-treat breast cancer cells and activated endothelial cells (tumor region), 3) significantly inhibit the growth and prevent from malignant metastasis of cancer cells in consonance with promising anti-tumor efficacy, and 4) keep tumors stick to localized position so that these confined solid tumors can be more accessible by different treatment modalities. The contribution of this work is how to design a programmable pH-responsive drug delivery system based on the tailor-designed polypeptides.

Graphical abstract

http://ift.tt/2s74FWL

Habenula and interpeduncular nucleus differentially modulate predator odor-induced innate fear behavior in rats

Publication date: 14 August 2017
Source:Behavioural Brain Research, Volume 332
Author(s): Daniel Vincenz, Kerstin E.A. Wernecke, Markus Fendt, Jürgen Goldschmidt
Fear is an important behavioral system helping humans and animals to survive potentially dangerous situations. Fear can be innate or learned. Whereas the neural circuits underlying learned fear are already well investigated, the knowledge about the circuits mediating innate fear is still limited. We here used a novel, unbiased approach to image in vivo the spatial patterns of neural activity in odor-induced innate fear behavior in rats. We intravenously injected awake unrestrained rats with a 99m-technetium labeled blood flow tracer (99mTc-HMPAO) during ongoing exposure to fox urine or water as control, and mapped the brain distribution of the trapped tracer using single-photon emission computed tomography (SPECT). Upon fox urine exposure blood flow increased in a number of brain regions previously associated with odor-induced innate fear such as the amygdala, ventromedial hypothalamus and dorsolateral periaqueductal grey, but, unexpectedly, decreased at higher significance levels in the interpeduncular nucleus (IPN). Significant flow changes were found in regions monosynaptically connected to the IPN. Flow decreased in the dorsal tegmentum and entorhinal cortex. Flow increased in the habenula (Hb) and correlated with odor effects on behavioral defensive strategy. Hb lesions reduced avoidance of but increased approach to the fox urine while IPN lesions only reduced avoidance behavior without approach behavior. Our study identifies a new component, the IPN, of the neural circuit mediating odor-induced innate fear behavior in mammals and suggests that the evolutionarily conserved Hb-IPN system, which has recently been implicated in cued fear, also forms an integral part of the innate fear circuitry.



http://ift.tt/2rWunuY

Fully automated breast boundary and pectoral muscle segmentation in mammograms

Publication date: Available online 9 June 2017
Source:Artificial Intelligence in Medicine
Author(s): Andrik Rampun, Philip J. Morrow, Bryan W. Scotney, John Winder
Breast and pectoral muscle segmentation is an essential pre-processing step for the subsequent processes in computer aided diagnosis (CAD) systems. Estimating the breast and pectoral boundaries is a difficult task especially in mammograms due to artifacts, homogeneity between the pectoral and breast regions, and low contrast along the skin-air boundary. In this paper, a breast boundary and pectoral muscle segmentation method in mammograms is proposed. For breast boundary estimation, we determine the initial breast boundary via thresholding and employ Active Contour Models without edges to search for the actual boundary. A post-processing technique is proposed to correct the overestimated boundary caused by artifacts. The pectoral muscle boundary is estimated using Canny edge detection and a pre-processing technique is proposed to remove noisy edges. Subsequently, we identify five edge features to find the edge that has the highest probability of being the initial pectoral contour and search for the actual boundary via contour growing. The segmentation results for the proposed method are compared with manual segmentations using 322, 208 and 100mammograms from the Mammographic Image Analysis Society (MIAS), INBreast and Breast Cancer Digital Repository (BCDR) databases, respectively. Experimental results show that the breast boundary and pectoral muscle estimation methods achieved dice similarity coefficients of 98.8% and 97.8% (MIAS), 98.9% and 89.6% (INBreast) and 99.2% and 91.9% (BCDR), respectively.



http://ift.tt/2sMLsY6

A hybrid framework for reverse engineering of robust Gene Regulatory Networks

Publication date: Available online 9 June 2017
Source:Artificial Intelligence in Medicine
Author(s): Mina Jafari, Behnam Ghavami, Vahid Sattari
The inference of Gene Regulatory Networks (GRNs) using gene expression data in order to detect the basic cellular processes is a key issue in biological systems. Inferring GRN correctly requires inferring predictor set accurately. In this paper, a fast and accurate predictor set inference framework which linearly combines some inference methods is proposed. The purpose of the combination of various methods is to increase the accuracy of inferred GRN. The proposed framework offers a linear weighted combination of Pearson Correlation Coefficient (PCC) and two different feature selection approaches, namely: Information Gain (IG) and ReliefF. In order to set the appropriate weights, Genetic Algorithm (GA) is used. Similarity measure is considered as fitness function to guide GA. At the end, based on the obtained weights, the best predictor set of GRN using three aforementioned inference methods is selected and the network topology is formed. Due to the huge volume of gene expression data, GRN inference algorithms should infer GRN at a reasonable runtime. Hence, a novel criterion is provided to evaluate GRNs based on runtime and accuracy. The simulation results using biological data indicate that the proposed framework is fast and more reliable compared to other recent methods [1–7].



http://ift.tt/2sds21L

Premature Ventricular Contraction Detection Combining Deep Neural Networks and Rules Inference

Publication date: Available online 9 June 2017
Source:Artificial Intelligence in Medicine
Author(s): Fei-yan Zhou, Lin-peng Jin, Jun Dong
Premature ventricular contraction (PVC), which is a common form of cardiac arrhythmia caused by ectopic heartbeat, can lead to life-threatening cardiac conditions. Computer-aided PVC detection is of considerable importance in medical centers or outpatient ECG rooms. In this paper, we proposed a new approach that combined deep neural networks and rules inference for PVC detection. The detection performance and generalization were studied using publicly available databases: the MIT-BIH arrhythmia database (MIT-BIH-AR) and the Chinese Cardiovascular Disease Database (CCDD). The PVC detection accuracy on the MIT-BIH-AR database was 99.41%, with a sensitivity and specificity of 97.59% and 99.54%, respectively, which were better than the results from other existing methods. To test the generalization capability, the detection performance was also evaluated on the CCDD. The effectiveness of the proposed method was confirmed by the accuracy (98.03%), sensitivity (96.42%) and specificity (98.06%) with the dataset over 140,000 ECG recordings of the CCDD.



http://ift.tt/2sN7RV9

Ameliorative effect of apelin on streptozotocin-induced diabetes and its associated cardiac hypertrophy

Publication date: Available online 9 June 2017
Source:Alexandria Journal of Medicine
Author(s): Islam Ibrahim Hegab
AimApelin, an adipocyte-derived factor, exhibited a number of cardioprotective properties; however, its effect in diabetes which is a major risk factor for cardiovascular disease (CVD) needs to be further studied. So this work was designed to evaluate the effect of apelin on diabetes and its associated cardiac hypertrophy with its possible underlying protective mechanisms.Experimental protocolThirty male adult Wistar rats were categorized into three groups, 10 rats each, normal control group: received standard food and water regime. Diabetic control group: received streptozotocin (STZ) at a dose of (55mg/kg, i.p., once) dissolved in citrate buffer (pH 4.5). Apelin-13 treated diabetic group: STZ diabetic rats received an intra peritoneal injection of apelin-13 at a dose of (100nmol/kg/day), and given daily for 8weeks. at the end of the experiment, oral glucose tolerance test (OGTT) was assayed, then rats were sacrificed and serum glucose, insulin, triglyceride (TG), total cholesterol, high density lipoprotein (HDL) cholesterol, serum lactate dehydrogenase (LDH) and serum creatine kinase – MB (CK-MB) were measured, together with cardiac hypertrophy index (CHI), left ventricular hypertrophy index (LVHI) and left ventricular protein and collagen content levels. Myocardial superoxide dismutase (SOD), catalase, reduced glutathione (GSH) and malondialdehyde (MDA) were determined in the myocardial tissue of experimental rats.ResultsTreatment with apelin-13 improved hyperglycemia and hyperlipidemia, and significantly protected against STZ-induced structural alterations in cardiac tissue, it also produced a significant reduction in MDA while it elevated the level of antioxidant enzymes in hearts of diabetic rats.ConclusionThis study suggested that apelin can ameliorate diabetes and its associated myocardial hypertrophy through mainly its anti diabetic, anti hyperlipidemic and anti oxidative stress properities.



http://ift.tt/2sdvJVa

Sharp foreign body ingestion by a young girl

Publication date: Available online 9 June 2017
Source:Alexandria Journal of Medicine
Author(s): Riyadh Mohamad Hasan
A 16year old patient had ingested two sewing needles about 4.5cm long accidentally that eventually resided in extra intestinal tract position, and being asymptomatic, she ignored the problem for a long period about 2years. She only consulted the hospital after having symptoms. The needles were located by X-ray imaging and retrieved with the aid of C-arm fluoroscope at a laparotomy. Her postoperative period was uneventful.



http://ift.tt/2sMub1d

Central Tibetan Plateau atmospheric trace metals contamination: A 500-year record from the Puruogangri ice core

Publication date: 1 December 2017
Source:Science of The Total Environment, Volumes 601–602
Author(s): Emilie Beaudon, Paolo Gabrielli, M. Roxana Sierra-Hernández, Anna Wegner, Lonnie G. Thompson
A ~500-year section of ice core (1497–1992) from the Puruogangri ice cap has been analyzed at high resolution for 28 trace elements (TEs: Ag, Al, As, Ba, Bi, Cd, Co, Cr, Cs, Cu, Fe, Ga, Li, Mg, Mn, Na, Nb, Ni, Pb, Rb, Sb, Sn, Sr, Ti, Tl, U, V and Zn) to assess different atmospheric contributions to the ice and provide a temporal perspective on the diverse atmospheric influences over the central Tibetan Plateau (TP). At least two volcanic depositions have significantly impacted the central TP over the past 500years, possibly originating from the Billy Mitchell (1580, Papua New Guinea) and the Parker Peak (1641, Philippines) eruptions. A decreasing aeolian dust input to the ice cap allowed the detection of an atmospheric pollution signal. The anthropogenic pollution contribution emerges in the record since the early 1900s (for Sb and Cd) and increases substantially after 1935 (for Ag, Zn, Pb, Cd and Sb). The metallurgy (Zn, Pb and steel smelting) emission products (Cd, Zn, Pb and Ag) from the former Soviet Union and especially from central Asia (e.g., Kyrgyzstan, Kazakhstan) likely enhanced the anthropogenic deposition to the Puruogangri ice cap between 1935 and 1980, suggesting that the westerlies served as a conveyor of atmospheric pollution to central Tibet. The impact of this industrial pollution cumulated with that of the hemispheric coal and gasoline combustion which are respectively traced by Sb and Pb enrichment in the ice. The Chinese steel production accompanying the Great Leap Forward (1958–1961) and the Chinese Cultural Revolution (1966–1976) is proposed as a secondary but proximal source of Pb pollution affecting the ice cap between 1958 and 1976. The most recent decade (1980–1992) of the enrichment time series suggests that Puruogangri ice cap recorded the early Sb, Cd, Zn, Pb and Ag pollution originating from developing countries of South (i.e., India) and East (i.e., China) Asia and transported by the summer monsoonal circulation.

Graphical abstract

http://ift.tt/2rflHxM

Potential impact of the Affordable Care Act's preventive services provision on breast cancer stage: A preliminary assessment

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Abigail Silva, Yamile Molina, Bijou Hunt, Talar Marossian, Nazia Saiyed
IntroductionThe Affordable Care Act's (ACA) preventive services provision (PSP) removes copayments for preventive services such as cancer screening. We examined: 1) whether a shift in breast cancer stage occurred, and 2) the impact of the provision on racial/ethnic disparities in stage.Materials and methodsData from the National Cancer Database were used. The pre- and post-PSP periods were identified as 2007–2009 and 2011–2013, respectively. Proportion differences (PDs) and 95% confidence Intervals (CIs) were calculated.ResultsAll three racial/ethnic groups experienced a statistically significant shift toward Stage I breast cancer. Pre-PSP, the black:white disparity in Stage I cancer was −9.5 (95% CI: −8.9, −10.4) and the Latina:white disparity was −5.2 (95% CI: −4.0, −6.1). Post-PSP, the disparities improved slightly.DiscussionPreliminary data suggest that the ACA's PSP may have a meaningful impact on cancer stage overall and by race/ethnicity. However, more time may be needed to see reductions in disparities.



http://ift.tt/2rLec59

Pollution and regional variations of lung cancer mortality in the United States

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Justin Xavier Moore, Tomi Akinyemiju, Henry E. Wang
IntroductionThe aims of this study were to identify counties in the United States (US) with high rates of lung cancer mortality, and to characterize the associated community-level factors while focusing on particulate-matter pollution.MethodsWe performed a descriptive analysis of lung cancer deaths in the US from 2004 through 2014. We categorized counties as "clustered" or "non-clustered" – based on whether or not they had high lung cancer mortality rates − using novel geospatial autocorrelation methods. We contrasted community characteristics between cluster categories. We performed logistic regression for the association between cluster category and particulate-matter pollution.ResultsAmong 362 counties (11.6%) categorized as clustered, the age-adjusted lung cancer mortality rate was 99.70 deaths per 100,000 persons (95%CI: 99.1–100.3). Compared with non-clustered counties, clustered counties were more likely in the south (72.9% versus 42.1%, P<0.01) and in non-urban communities (73.2% versus 57.4, P<0.01). Clustered counties had greater particulate-matter pollution, lower education and income, higher rates of obesity and physical inactivity, less access to healthcare, and greater unemployment rates (P<0.01). Higher levels of particulate-matter pollution (4th quartile versus 1st quartile) were associated with two-fold greater odds of being a clustered county (adjusted OR: 2.10; 95%CI: 1.23–3.59).ConclusionWe observed a belt of counties with high lung mortality ranging from eastern Oklahoma through central Appalachia; these counties were characterized by higher pollution, a more rural population, lower socioeconomic status and poorer access to healthcare. To mitigate the burden of lung cancer mortality in the US, both urban and rural areas should consider minimizing air pollution.



http://ift.tt/2rfzCUz

Socioeconomic measures influence survival in osteosarcoma: an analysis of the National Cancer Data Base

Publication date: August 2017
Source:Cancer Epidemiology, Volume 49
Author(s): Benjamin J. Miller, Yubo Gao, Kyle R. Duchman
BackgroundWhile previous studies have identified low socioeconomic status as a risk factor for metastatic disease in patients with high-grade osteosarcoma, the influence of socioeconomic status on overall survival remains unclear. The present study aims to investigate the relationship between survival and socioeconomic status in patients with high-grade conventional osteosarcoma.MethodsThe National Cancer Data Base (NCDB) was queried from 1998-2012 to identify all patients <40years of age with a diagnosis of high-grade conventional osteosarcoma. A total of 3,503 patients were identified that met inclusion and exclusion criteria. Univariate relationships were investigated using Kaplan-Meier survival analysis and associated log-rank tests in order to determine patient, socioeconomic, tumor, and treatment variables associated with overall survival. Multivariate analysis was performed to determine independent predictors of survival.ResultsIn order of decreasing magnitude, metastatic disease (Hazard Ratio [HR] 3.28, 95% Confidence Interval [CI] 2.82-3.82), primary site in the pelvis or spine (HR 2.15, 95% CI 1.79-2.59), positive surgical margins (HR 1.82, 95% CI 1.46-2.27), tumor size >8cm (HR 1.47, 95% CI 1.24-1.74), age ≥18 years (HR 1.30, 95% CI 1.14-1.48), lowest quartile of composite socioeconomic status (HR 1.23, 95% CI 1.02-1.51), and Medicaid insurance (HR 1.18, 95% CI 1.02-1.38) were predictors of decreased survival at 5 years.ConclusionTreating providers should be aware that some of their patients may have challenges unrelated to their diagnosis that make timely presentation, adherence to treatment, and continued close surveillance difficult. This investigation suggests that socioeconomic variables influence overall survival for osteosarcoma in the United States, although not as dramatically as established tumor- and treatment-related risk factors.



http://ift.tt/2rKU9DO

Natural radionuclides in plants, soils and sediments affected by U-rich coal mining activities in Brazil

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): Juliana Aparecida Galhardi, Rafael García-Tenorio, Daniel Marcos Bonotto, Inmaculada Díaz Francés, João Gabriel Motta
Mining activities can increase the mobility of metals by accelerating the dissolution and leaching of minerals from the rocks and tailing piles to the environment and, consequently, their availability for plants and subsequent transfer to the food chain. The weathering of minerals and the disposal of coal waste in tailing piles can accelerate the generation of acid mine drainage (AMD), which is responsible for the higher dissolution of metals in mining areas. In this context, the behavior of U, Th and K in soils and sediment, and the transfer factor (TF) of ²³⁸U, ²³⁴U and ²¹⁰Po for soybean, wheat, pine and eucalyptus cultivated around a coal mine in southern Brazil was evaluated. Alpha and gamma spectrometry were used for the measurements of the activity concentration of the radioelements. ²¹⁰Po was the radionuclide that is most accumulated in the plants, especially in the leaves. When comparing the plant species, pine showed the highest TF values for ²³⁴U (0.311 ± 0.420) for leaves, while eucalyptus showed the highest TF for ²³⁸U (0.344 ± 0.414) for leaves. In general, TF were higher for the leaves of soybean and wheat when compared to the grains, and grains of wheat showed higher TF for ²¹⁰Po and ²³⁸U than grains of soybean. Deviations from the natural U isotopic ratio were recorded at all investigated areas, indicating possible industrial and mining sources of U for the vegetables. A safety assessment of transport routes and accumulation of radionuclides in soils with a potential for cultivation is important, mainly in tropical areas contaminated with solid waste and effluents from mines and industry.

Graphical abstract

http://ift.tt/2rbzBFQ

Preoperative pregabalin or gabapentin for postoperative acute and chronic pain among patients undergoing breast cancer surgery: A systematic review and meta-analysis of randomized controlled trials

Breast cancer surgery is associated with acute and chronic pain. We sought to systematically evaluate the effect of gabapentin and pregabalin on post-surgical pain among patients undergoing breast cancer surgery.

http://ift.tt/2t4AexG

“3D Bioprinting for Reconstructive Surgery: Principles, Applications and Challenges”

Despite the increasing laboratory research in the growing field of 3D bioprinting there are few reports of successful translation into surgical practice. This review outlines the principles of 3D bioprinting including software and hardware processes, biocompatible technological platforms and suitable bioinks. The advantages of 3D bioprinting over traditional tissue engineering techniques in assembling cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nano-architecture is discussed, together with an overview of current progress in bioprinting tissue types relevant for plastic and reconstructive surgery.

http://ift.tt/2s6yYwy

“A higher quality of life with cross-face-nerve-grafting as an adjunct to a hypoglossal-facial jump graft in facial palsy treatment.”

Nerve reconstructions are the preferred technique for short standing facial paralysis, most commonly using the contralateral facial nerve or ipsilateral hypoglossal nerve. The hypoglossal nerve gives a strong motor signal. The signal of a cross-face nerve graft is weaker, but spontaneous. Spontaneity in facial expression is believed to be of importance for psychological wellbeing. Therefore combination of the two procedures combines the best of both: a strong motor signal and a spontaneous smile.

http://ift.tt/2s6RLb3

Breast reconstruction by exclusive fat grafting: what about the breast projection?

Autologous fat grafting in exclusive breast reconstruction has been booming in recent years (1,2). This technique has many advantages (autologous reconstruction, reduced scar, absence of muscle sample) as well as a secondary benefit on the improvement of patient silhouette. Its main disadvantage is still the need for performing several successive procedures under general anesthesia, most often to achieve a satisfactory breast volume.

http://ift.tt/2t4HcCO

Body Contouring Procedures in Three or More Anatomical Areas are Associated with Long Term Body Mass Index Decrease in Massive Weight Loss Patients - a retrospective cohort study

– Massive weight loss (MWL) patients who undergo body contouring plastic surgery (BCPS) display superior long-term weight maintenance. The effect of the number of anatomical areas contoured on weight dynamics is undetermined.

http://ift.tt/2s6uiqw

Fishing bacteria with a nanonet

Publication date: Available online 9 June 2017
Source:Materials Today
Author(s): F. De Cesare, E. Di Mattia, A. Macagnano




http://ift.tt/2rKHqBf

Adiponectin: its role in obesity-associated colon and prostate cancers

Publication date: Available online 9 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Santoshi Muppala, Siva KP Konduru, Neha Merchant, Judy Ramsoondar, Carlos Karan Rampersad, Balney Rajitha, Vidya Mukund, Jyothsna Kancherla, Anthea Hammond, Tapan Kumar Barik, Mastan Mannarapu, Afroz Alam, Riyaz Basha, Pallavula Veera Bramhachari, Dheeraj Verma, Pinninti Santosh Sushma, Subasini Pattnaik, Ganji Purnachandra Nagaraju
Adipose tissue synthesizes many proteins and hormones collectively called adipokines, which are linked to a number of diseases, including cancer. Low levels of adiponectin are reported to be a risk factor for obesity-related cancers including colorectal and prostate cancers. Accordingly, obesity/lifestyle-related diseases, including certain cancers, may be treated by developing drugs that act specifically on adiponectin levels in circulation. Adiponectin may also serve as a clinical biomarker in obesity-related diseases. Adiponectin-based therapies are known to inhibit cancer advancement and thus may provide a therapeutic approach to delay cancer progression. Better understanding of the function of adiponectin is of great significance in the fight against cancer. This timely review is concentrated on the role of adiponectin and the impact of obesity on the development of cancers, especially colorectal and prostate cancers.



http://ift.tt/2rb5QVL

BIOMARKERS OF RESPONSE TO PD-1/PD-L1 INHIBITION

Publication date: Available online 6 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Saman Maleki Vareki, Carmen Garrigós, Ignacio Duran
Immunotherapy is a promising treatment strategy for cancer that has recently shown unprecedented survival benefits in selected patients. A number of immunomodulatory agents that target immune system checkpoints such as the cytotoxic T-lymphocyte antigen 4 (CTLA-4), the programmed death-1 (PD-1) or its ligand (PD-L1), have received regulatory approval for the treatment of multiple cancers including malignant melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, and recurrent or metastatic head and neck squamous cell carcinoma. Nevertheless, a substantial proportion of patients treated with checkpoint inhibitors have little or no benefit while these treatments are costly and might have associated toxicities. Hence, the establishment of valid predictors of treatment response has become a priority. This review summarizes the current evidence around biomarkers of response to PD-1/PD-L1 inhibition, considering features related to the tumor and to the host immune system.



http://ift.tt/2rVLInx

Hybrid 18 F–FDG PET/MRI might improve locoregional staging of breast cancer patients prior to neoadjuvant chemotherapy

Abstract

Purpose

Our purpose in this study was to assess the added clinical value of hybrid ¹⁸F–FDG-PET/MRI compared to conventional imaging for locoregional staging in breast cancer patients undergoing neoadjuvant chemotherapy (NAC).

Methods

In this prospective study, primary invasive cT2-4 N0 or cT1-4 N+ breast cancer patients undergoing NAC were included. A PET/MRI breast protocol was performed before treatment. MR images were evaluated by a breast radiologist, blinded for PET images. PET images were evaluated by a nuclear physician. Afterwards, a combined PET/MRI report was written. PET/MRI staging was compared to conventional imaging, i.e., mammography, ultrasound and MRI. The proportion of patients with a modified treatment plan based on PET/MRI findings was analyzed.

Results

A total of 40 patients was included. PET/MRI was of added clinical value in 20.0% (8/40) of patients, changing the treatment plan in 10% and confirming the malignancy of suspicious lesions on MRI in another 10%. In seven (17.5%) patients radiotherapy fields were extended because of additional or affirmative PET/MRI findings being lymph node metastases (n = 5) and sternal bone metastases (n = 2). In one (2.5%) patient radiotherapy fields were reduced because of fewer lymph node metastases on PET/MRI compared to conventional imaging. Interestingly, all treatment changes were based on differences in number of lymph nodes suspicious for metastasis or number of distant metastasis, whereas differences in intramammary tumor extent were not observed.

Conclusion

Prior to NAC, PET/MRI shows promising results for locoregional staging compared to conventional imaging, changing the treatment plan in 10% of patients and potentially replacing PET/CT or tissue sampling in another 10% of patients.

http://ift.tt/2rVBAeJ

Changes in cortical excitability during paired associative stimulation in Parkinson's disease patients and healthy subjects

Publication date: Available online 9 June 2017
Source:Neuroscience Research
Author(s): Aleksandra Kačar, Sladjan D. Milanović, Saša R. Filipović, Miloš R. Ljubisavljević
Paired associative stimulation (PAS) combines repetitive peripheral nerve stimulation with motor cortex (M1) transcranial magnetic stimulation (TMS), to induce plastic-like changes of cortical excitability. While much attention has been dedicated to post-PAS effects little is known about processes during PAS. We compared the time-course of changes in M1 excitability during standard facilitatory PAS intervention among patients with Parkinson's disease (PD), known to have diminished post-PAS response, and healthy subjects. Compared to baseline pre-PAS MEPs, conditioned MEPs during PAS decreased significantly in both groups. The decrease was significantly larger in healthy subjects than in PD patients, regardless whether patients were drug-naïve or not. Although post-PAS excitability increase was also larger in healthy subjects than in PD patients, there was no significant correlation between the two phenomena, i.e. the extent of MEP decrease during PAS and the extent of the post-PAS excitability increase. The results highlight an apparent physiological paradox that repetitive application of an inhibitory stimulation pattern leads to subsequent prolonged facilitation, thus broadening the understanding of the phenomenology of PAS response. Results also suggest that in PD cortical circuits involved in conveying inhibition during PAS, are impaired at the clinical onset of the disease and are not influenced by subsequent PD treatment.



http://ift.tt/2rKeARg

Visual Discrimination and Reversal Learning in Aged Common Marmosets (Callithrix jacchus)

Publication date: Available online 9 June 2017
Source:Neuroscience Research
Author(s): Emily L. Munger, Atsushi Takemoto, Mary Ann Raghanti, Katsuki Nakamura
Common marmosets (Callithrix jacchus) have been suggested as a new model for analysis of age-related changes and neurodegenerative diseases. However, the effects of age on learning and memory processes are not well defined within this species. Therefore, we employed visual discrimination and reversal learning tasks to evaluate learning and memory in four aged common marmosets relative to a younger cohort. We found that aged marmosets commit significantly more errors in initial stages of visual discrimination and more perseverative errors in reversal learning, indicating prefrontal dysfunction. However, they showed comparable performance with younger marmosets in the later stages of both tasks.



http://ift.tt/2reUCuG

Inside front cover

Publication date: 1 September 2017
Source:Talanta, Volume 172





http://ift.tt/2r4crgA

Inside front cover

Publication date: 1 October 2017
Source:Talanta, Volume 173





http://ift.tt/2snaD6t

Editorial Board

Publication date: 1 October 2017
Source:Talanta, Volume 173





http://ift.tt/2r4cr04

Editorial Board

Publication date: 1 September 2017
Source:Talanta, Volume 172





http://ift.tt/2smZH8Q

rTMS with a two-coil array: Safety and efficacy for treatment resistant major depressive disorder

Publication date: Available online 9 June 2017
Source:Brain Stimulation
Author(s): Linda L. Carpenter, Scott T. Aaronson, Gregory N. Clarke, Paul E. Holtzheimer, Clark W. Johnson, William M. McDonald, Elizabeth L. Stannard, M.Brett Schneider
BackgroundTherapeutic repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as a standard of care for individuals with major depressive disorder (MDD) who do not benefit from, or are unable to tolerate, antidepressant pharmacotherapy. Depth of stimulation is limited with currently approved figure-eight coils and larger coils capable of deeper penetration may be associated with loss of stimulation focality and undesired recruitment of motor cortex. A second generation 2-coil array rTMS system was designed to target converging brain pathways for potentially deeper prefrontal cortex stimulation.MethodsA randomized, double-blind, sham-controlled trial examined the safety and efficacy of an investigational 2-coil rTMS device. Antidepressant treatment-resistant or treatment-intolerant MDD patients (n=92) received 20 daily rTMS treatments with coil centers positioned over left dorsolateral prefrontal cortex (dlPFC) and dorsomedial prefrontal cortex (dmPFC). 10 Hz stimulation (maximum summated power for both coils ≤ 120% motor threshold) was delivered. Primary efficacy endpoint was change in HAMD-24 score from baseline to the conclusion of treatments.ResultsData from n=75 (per-protocol sample) showed significantly greater improvement (mean HAMD-24 change) over time for the active (n=38) versus sham (n=37) group after 20 sessions (F = 7.174; p = .008) and also at the one-month follow-up (F = 6.748; p = .010).Response rates were 55.3% (active) versus 32.4% (sham) (p=.063); remission rates were 26.3% versus 18.9% (p>.05). Other secondary outcomes were generally supportive.ConclusionsThe results confirmed safety and acute efficacy of the 2-coil rTMS device. Despite modest sample size, primary outcome was clinically and statistically significant, and the effect size was comparable with those reported for regulatory trials with FDA-cleared devices.



http://ift.tt/2raQala

Neuropsychological and psychiatric outcome of GPi-deep brain stimulation in dystonia

Publication date: Available online 9 June 2017
Source:Brain Stimulation
Author(s): Claudio M. de Gusmao, Lauren E. Pollak, Nutan Sharma
BackgroundPrevious investigators have observed changes in cognitive and psychiatric domains after GPi-DBS for dystonia, such as declines in semantic verbal fluency and set shifting or increased suicidality. Others have reported stability or improvements in select areas, such as graphomotor speed and mood. Interpretation of these findings is limited by inclusion of select patient populations or limited neuropsychological testing.ObjectiveTo describe cognitive and neuropsychiatric outcomes in a cohort of patients with primary and secondary dystonia undergoing Globus Pallidus pars interna deep brain stimulation (GPi-DBS).MethodsPatients with primary and secondary dystonia were evaluated at baseline and post-operatively with a comprehensive battery of neuropsychological tests and mood inventories including anxiety, depression and hopelessness scales. Statistical significance was calculated with one-tailed student t-test, defined as p value < 0.05.ResultsTwelve patients were included in the study. Nine were male (75%) and the mean age at baseline assessment was 42.3 years (range 13 – 68; SD 18.0). The majority had focal or segmental dystonia (8/12, 66%), 4 patients had generalized dystonia. Three patients had monogenic dystonias (DYT 1 and DYT 3), and two patients had acquired (tardive) dystonia. Mean time between surgery and follow-up was 13.1 months (SD 3.1). Subjects demonstrated stable performance on most tests, with statistically significant improvements noted in working memory (letter-number sequencing), executive function (trail-making B), anxiety and depression.ConclusionsIn an etiologically and clinically diverse patient population, administration of comprehensive battery of cognitive tests pre and post-operatively suggests that GPi-DBS is safe from cognitive and psychiatric perspectives.



http://ift.tt/2rVt3Z7

Replicative DNA polymerase defects in human cancers: consequences, mechanisms, and implications for therapy

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Stephanie R. Barbari, Polina V. Shcherbakova
The fidelity of DNA replication relies on three error avoidance mechanisms acting in series: nucleotide selectivity of replicative DNA polymerases, exonucleolytic proofreading, and post-replicative DNA mismatch repair (MMR). MMR defects are well known to be associated with increased cancer incidence. Due to advances in DNA sequencing technologies, the past several years have witnessed a long-predicted discovery of replicative DNA polymerase defects in sporadic and hereditary human cancers. The polymerase mutations preferentially affect conserved amino acid residues in the exonuclease domain and occur in tumors with an extremely high mutation load. Thus, a concept has formed that defective proofreading of replication errors triggers the development of these tumors. Recent studies of the most common DNA polymerase variants, however, suggested that their pathogenicity may be determined by functional alterations other than loss of proofreading. In this review, we summarize our current understanding of the consequences of DNA polymerase mutations in cancers and the mechanisms of their mutator effects. We also discuss likely explanations for a high recurrence of some but not other polymerase variants and new ideas for therapeutic interventions emerging from the mechanistic studies.



http://ift.tt/2rJOQo4

Mechanistic Insights into Transcription Coupled DNA Repair

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Bibhusita Pani, Evgeny Nudler
Transcription-coupled DNA repair (TCR) acts on lesions in the transcribed strand of active genes. Helix distorting adducts and other forms of DNA damage often interfere with the progression of the transcription apparatus. Prolonged stalling of RNA polymerase can promote genome instability and also induce cell cycle arrest and apoptosis. These generally unfavorable events are counteracted by RNA polymerase-mediated recruitment of specific proteins to the sites of DNA damage to perform TCR and eventually restore transcription. In this perspective we discuss the decision-making process to employ TCR and we elucidate the intricate biochemical pathways leading to TCR in E. coli and human cells.



http://ift.tt/2reNf6x

Role of recombination and replication fork restart in repeat instability

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Erica J. Polleys, Nealia C.M. House, Catherine H. Freudenreich
Eukaryotic genomes contain many repetitive DNA sequences that exhibit size instability. Some repeat elements have the added complication of being able to form secondary structures, such as hairpin loops, slipped DNA, triplex DNA or G-quadruplexes. Especially when repeat sequences are long, these DNA structures can form a significant impediment to DNA replication and repair, leading to DNA nicks, gaps, and breaks. In turn, repair or replication fork restart attempts within the repeat DNA can lead to addition or removal of repeat elements, which can sometimes lead to disease. One important DNA repair mechanism to maintain genomic integrity is recombination. Though early studies dismissed recombination as a mechanism driving repeat expansion and instability, recent results indicate that mitotic recombination is a key pathway operating within repetitive DNA. The action is two-fold: first, it is an important mechanism to repair nicks, gaps, breaks, or stalled forks to prevent chromosome fragility and protect cell health; second, recombination can cause repeat expansions or contractions, which can be deleterious. In this review, we summarize recent developments that illuminate the role of recombination in maintaining genome stability at DNA repeats.



http://ift.tt/2rKeObd

Structural and Functional Relationships of FAN1

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Hyeonseok Jin, Yunje Cho
FANCD2/FANCI-associated nuclease (FAN1) is a 5′ flap structure-specific endonuclease and 5′ to 3′ exonuclease. This nuclease can resolve interstrand cross-links (ICLs) independently of the Fanconi anemia (FA) pathway and controls the progression of stalled replication forks in an FA-dependent manner, thereby maintaining chromosomal stability. Several FAN1 mutations are observed in various cancers and degenerative diseases. Recently, several crystal structures of the FAN1-DNA complexes have been reported, and to date, these represent the only structures for a DNA bound ICL-repair nuclease. Puzzlingly, human FAN1 forms two different quaternary structures with different DNA binding modes, and based on these structures, two ICL-repair mechanisms have been proposed. In one mechanism, monomeric FAN1 recognizes the 5′ flap terminal phosphate via a basic pocket and successively cleaves at every third nucleotide of the DNA substrates. In the other mechanism, dimeric FAN1 scans, latches, and unwinds the postnick duplex of the substrate DNA to direct the scissile phosphodiester group to the active site. In this review, we discuss the structures, function, and proposed mechanisms of FAN1 nuclease, and provide the insights into its role in ICL repair and in processing of stalled replication forks.



http://ift.tt/2rJQXrX

DNA requirements for interaction of the C-terminal region of Ku80 with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs)

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Sarvan Kumar Radhakrishnan, Susan P. Lees-Miller
Non-homologous end joining (NHEJ) is the major pathway for the repair of ionizing radiation induced DNA double strand breaks (DSBs) in human cells. Critical to NHEJ is the DNA-dependent interaction of the Ku70/80 heterodimer with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the DNA-PK holoenzyme. However, precisely how Ku recruits DNA-PKcs to DSBs ends to enhance its kinase activity has remained enigmatic, with contradictory findings reported in the literature. Here we address the role of the Ku80 C-terminal region (CTR) in the DNA-dependent interaction of Ku70/80 with DNA-PKcs using purified components and defined DNA structures. Our results show that the Ku80 CTR is required for interaction with DNA-PKcs on short segments of blunt ended 25bp dsDNA or 25bp dsDNA with a 15-base poly dA single stranded (ss) DNA extension, but this requirement is less stringent on longer dsDNA molecules (35bp blunt ended dsDNA) or 25bp duplex DNA with either a 15-base poly dT or poly dC ssDNA extension. Our work clarifies the role of the Ku80 CTR and dsDNA ends on the interaction of DNA-PKcs with Ku and provides key information to guide assembly and biology of NHEJ complexes.



http://ift.tt/2reu6S8

BERing the burden of damage: Pathway crosstalk and posttranslational modification of base excision repair proteins regulate DNA damage management

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Kristin Limpose, Anita H. Corbett, Paul W. Doetsch
DNA base damage and non-coding apurinic/apyrimidinic (AP) sites are ubiquitous types of damage that must be efficiently repaired to prevent mutations. These damages can occur in both the nuclear and mitochondrial genomes. Base excision repair (BER) is the frontline pathway for identifying and excising damaged DNA bases in both of these cellular compartments. Recent advances demonstrate that BER does not operate as an isolated pathway but rather dynamically interacts with components of other DNA repair pathways to modulate and coordinate BER functions. We define the coordination and interaction between DNA repair pathways as pathway crosstalk. Numerous BER proteins are modified and regulated by post-translational modifications (PTMs), and PTMs could influence pathway crosstalk. Here, we present recent advances on BER/DNA repair pathway crosstalk describing specific examples and also highlight regulation of BER components through PTMs. We have organized and reported functional interactions and documented PTMs for BER proteins into a consolidated summary table. We further propose the concept of DNA repair hubs that coordinate DNA repair pathway crosstalk to identify central protein targets that could play a role in designing future drug targets.



http://ift.tt/2rJRNFk

CtIP/Ctp1/Sae2, Molecular Form Fit For Function

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Sara N. Andres, R. Scott Williams
Vertebrate CtIP, and its fission yeast (Ctp1), budding yeast (Sae2) and plant (Com1) orthologs have emerged as key regulatory molecules in cellular responses to DNA double strand breaks (DSBs). By modulating the nucleolytic 5′-3′ resection activity of the Mre11/Rad50/Nbs1 (MRN) DSB repair processing and signaling complex, CtIP/Ctp1/Sae2/Com1 is integral to the channeling of DNA double strand breaks through DSB repair by homologous recombination (HR). Nearly two decades since its discovery, emerging new data are defining the molecular underpinnings for CtIP DSB repair regulatory activities. CtIP homologs are largely intrinsically unstructured proteins comprised of expanded regions of low complexity sequence, rather than defined folded domains typical of DNA damage metabolizing enzymes and nucleases. A compact structurally conserved N-terminus forms a functionally critical tetrameric helical dimer of dimers (THDD) region that bridges CtIP oligomers, and is flexibly appended to a conserved C-terminal Sae2-homology DNA binding and DSB repair pathway choice regulatory hub which influences nucleolytic activities of the MRN core nuclease complex. The emerging evidence from structural, biophysical, and biological studies converges on CtIP having functional roles in DSB repair that include: 1) dynamic DNA strand coordination through direct DNA binding and DNA bridging activities, 2) MRN nuclease complex cofactor functions that direct MRN endonucleolytic cleavage of protein-blocked DSB ends and 3) acting as a protein binding hub targeted by the cell cycle regulatory apparatus, which influences CtIP expression and activity via layers of post-translational modifications, protein-protein interactions and DNA binding.



http://ift.tt/2rf2GLS

8-Oxo-7,8-dihydroguanine, friend and foe: Epigenetic-like regulator versus initiator of mutagenesis

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Aaron M. Fleming, Cynthia J. Burrows
A high flux of reactive oxygen species during oxidative stress results in oxidative modification of cellular components including DNA. Oxidative DNA "damage" to the heterocyclic bases is considered deleterious because polymerases may incorrectly read the modifications causing mutations. A prominent member in this class is the oxidized guanine base 8-oxo-7,8-dihydroguanine (OG) that is moderately mutagenic effecting G→T transversion mutations. Recent reports have identified that formation of OG in G-rich regulatory elements in the promoters of the VEGF, TNFα, and SIRT1 genes can increase transcription via activation of the base excision repair (BER) pathway. Work in our laboratory with the G-rich sequence in the promoter of VEGF concluded that BER drives a shift in structure to a G-quadruplex conformation leading to gene activation in mammalian cells. More specifically, removal of OG from the duplex context by 8-oxoguanine glycosylase 1 (OGG1) produces an abasic site (AP) that destabilizes the duplex, shifting the equilibrium toward the G-quadruplex fold because of preferential extrusion of the AP into a loop. The AP is bound but inefficiently cleaved by apurinic/apyrimidinic endoDNase I (APE1) that likely allows recruitment of activating transcription factors for gene induction. The ability of OG to induce transcription ascribes a regulatory or epigenetic-like role for this oxidatively modified base. We compare OG to the 5-methylcytosine (5mC) epigenetic pathway including its oxidized derivatives, some of which poise genes for transcription while also being substrates for BER. The mutagenic potential of OG to induce only ∼one-third the number of mutations (G→T) compared to deamination of 5mC producing C→T mutations is described. These comparisons blur the line between friendly epigenetic base modifications and those that are foes, i.e. DNA "damage," causing genetic mutations.



http://ift.tt/2rJROcm

Unveiling the non-repair face of the base excision repair pathway in RNA processing: A missing link between DNA repair and gene expression?

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Giulia Antoniali, Matilde Clarissa Malfatti, Gianluca Tell
The Base Excision Repair (BER) pathway, initially studied as a mere DNA repair pathway, has been later found to be implicated in the expression of cancer related genes in human. For several years, this intricate involvement in apparently different processes represented a mystery, which we now are starting to unveil.The BER handles simple alkylation and oxidative lesions arising from both endogenous and exogenous sources, including cancer therapy agents. Surprisingly, BER pathway involvement in transcriptional regulation, immunoglobulin variability and switch recombination, RNA metabolism and nucleolar function is astonishingly consolidating. An emerging evidence in tumor biology is that RNA processing pathways participate in DNA Damage Response (DDR) and that defects in these regulatory connections are associated with genomic instability of cancers. In fact, many BER proteins are associated with those involved in RNA metabolism, ncRNA processing and transcriptional regulation, including within the nucleolus, proving a substantial role of the interactome network in determining their non-canonical functions in tumor cells. Maybe these new insights of BER enzymes, along with their emerging function in RNA-decay, may explain BER essential role in tumor development and chemoresistance and may explain the long-time mystery. Here, we would like to summarize different roles of BER pathway in human cells. First, we will give a short description of the classical BER pathway, which has been covered in detail in recent reviews. We will then outline potential new roles of BER in gene expression and RNA metabolism. Although recent works have provided tremendous amount of data in this field, there are still lot of open questions.



http://ift.tt/2reNbUl

Dormant origins as a built-in safeguard in eukaryotic DNA replication against genome instability and disease development

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Naoko Shima, Kayla D. Pederson
DNA replication is a prerequisite for cell proliferation, yet it can be increasingly challenging for a eukaryotic cell to faithfully duplicate its genome as its size and complexity expands. Dormant origins now emerge as a key component for cells to successfully accomplish such a demanding but essential task. In this perspective, we will first provide an overview the fundamental processes eukaryotic cells have developed to regulate origin licensing and firing. With a special focus on mammalian systems, we will then highlight the role of dormant origins in preventing replication-associated genome instability and their functional interplay with proteins involved in the DNA damage repair response for tumor suppression. Lastly, deficiencies in the origin licensing machinery will be discussed in relation to its influence on stem cell maintenance and human diseases.



http://ift.tt/2rK1Pq9

DNA Repair and Systemic Lupus Erythematosus

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Rithy Meas, Matthew J. Burak, Joann B. Sweasy
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with no known cure that affects at least five million people worldwide. Monozygotic twin concordance and familial aggregation studies strongly suggest that lupus results from genetic predisposition along with environmental exposures including UV light. The majority of the common risk alleles associated with genetic predisposition to SLE map to genes associated with the immune system. However, evidence is emerging that implicates a role for aberrant DNA repair in the development of lupus. Here we summarize our current knowledge of the potential association of lupus with mutations in DNA repair genes. We also discuss how defective or aberrant DNA repair could lead to the development of lupus.



http://ift.tt/2reAQ2l

Poetry in motion: Increased chromosomal mobility after DNA damage

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Michael J. Smith, Rodney Rothstein
Double-strand breaks (DSBs) are among the most lethal DNA lesions, and a variety of pathways have evolved to manage their repair in a timely fashion. One such pathway is homologous recombination (HR), in which information from an undamaged donor site is used as a template for repair. Although many of the biochemical steps of HR are known, the physical movements of chromosomes that must underlie the pairing of homologous sequence during mitotic DSB repair have remained mysterious. Recently, several groups have begun to use a variety of genetic and cell biological tools to study this important question. These studies reveal that both damaged and undamaged loci increase the volume of the nuclear space that they explore after the formation of DSBs. This DSB-induced increase in chromosomal mobility is regulated by many of the same factors that are important during HR, such as ATR-dependent checkpoint activation and the recombinase Rad51, suggesting that this phenomenon may facilitate the search for homology. In this perspective, we review current research into the mobility of chromosomal loci during HR, as well as possible underlying mechanisms, and discuss the critical questions that remain to be answered. Although we focus primarily on recent studies in the budding yeast, Saccharomyces cerevisiae, examples of experiments performed in higher eukaryotes are also included, which reveal that increased mobility of damaged loci is a process conserved throughout evolution.



http://ift.tt/2rJOJsE

Histone ubiquitination in the DNA damage response

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Michael Uckelmann, Titia K. Sixma
DNA double strand breaks need to be repaired in an organized fashion to preserve genomic integrity. In the organization of faithful repair, histone ubiquitination plays a crucial role. Recent findings suggest an integrated model for DNA repair regulation through site-specific histone ubiquitination and crosstalk to other posttranslational modifications. Here we discuss how site-specific histone ubiquitination is achieved on a molecular level and how different multi-protein complexes work together to integrate different histone ubiquitination states. We propose a model where site-specific H2A ubiquitination organizes the spatio-temporal recruitment of DNA repair factors which will ultimately contribute to DNA repair pathway choice between homologous recombination and non-homologous end joining.



http://ift.tt/2relvPk

The Top1 paradox: friend and foe of the eukaryotic genome

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Nayun Kim, Sue Jinks-Robertson
Topoisomerases manage the torsional stress associated with the separation of DNA strands during transcription and DNA replication. Eukaryotic Topoisomerase I (Top1) is a Type IB enzyme that nicks and rejoins only one strand of duplex DNA, and it is especially important during transcription. By resolving transcription-associated torsional stress, Top1 reduces the accumulation of genome-destabilizing R-loops and non-B DNA structures. The DNA nicking activity of Top1, however, can also initiate genome instability in the form of illegitimate recombination, homologous recombination and mutagenesis. In this review, we focus on the diverse, and often opposing, roles of Top1 in regulating eukaryotic genome stability.



http://ift.tt/2rJX2ot

Close encounters: moving along bumps, breaks, and bubbles on expanded trinucleotide tracts

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Aris Polyzos, Cynthia McMurray
Expansion of simple triplet repeats (TNR) underlies more than 30 severe degenerative diseases. There is a good understanding of the major pathways generating an expansion, and the associated polymerases that operate during gap filling synthesis at these "difficult to copy" sequences. However, the mechanism by which a TNR is repaired depends on the type of lesion, the structural features imposed by the lesion, the assembled replication/repair complex, and the polymerase that encounters it. The relationships among these parameters are exceptionally complex and how they direct pathway choice is poorly understood. In this review, we consider the properties of polymerases, and how encounters with GC-rich or abnormal structures might influence polymerase choice and the success of replication and repair. Insights over the last three years have highlighted new mechanisms that provide interesting choices to consider in protecting genome stability.



http://ift.tt/2reARmV

Evolutionary Dynamics and Significance of Multiple Subclonal Mutations in Cancer

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Robert A. Beckman, Lawrence A. Loeb
For the last 40 years the authors have collaborated on trying to understand the complexities of human cancer by formulating testable mathematical models that are based on mutation accumulation in human malignancies. We summarize the concepts encompassed by multiple mutations in human cancers in the context of source, accumulation during carcinogenesis and tumor progression, and therapeutic consequences. We conclude that the efficacious treatment of human cancer by targeted therapy will involve individualized, uniquely directed specific agents singly and in simultaneous combinations, and take into account the importance of targeting resistant subclonal mutations, particularly those subclones with alterations in DNA repair genes, DNA polymerase, and other genes required to maintain genetic stability.



http://ift.tt/2rJVpXY

Taming Tricky DSBs: ATM on duty

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Thomas Clouaire, Aline Marnef, Gaëlle Legube
Ataxia Telangiectasia Mutated (ATM) has been known for decades as the main kinase mediating the DNA Double-Strand Break Response (DDR). Extensive studies have revealed its dual role in locally promoting detection and repair of DSBs as well as in activating global DNA damage checkpoints. However, recent studies pinpoint additional unanticipated functions for ATM in modifying both the local chromatin landscape and the global chromosome organization, more particularly at persistent breaks. Given the emergence of a novel and unexpected class of DSBs prevalently arising in transcriptionally active genes and intrinsically difficult to repair, a specific role of ATM at refractory DSBs could be an important and so far overlooked feature of Ataxia Telangiectasia (A-T) a severe disorder associated with ATM mutations.



http://ift.tt/2reo7fS

Genome Instabilities Arising from Ribonucleotides in DNA

Publication date: Available online 9 June 2017
Source:DNA Repair
Author(s): Hannah L. Klein
Genomic DNA is transiently contaminated with ribonucleotide residues during the process of DNA replication through misincorporation by the replicative DNA polymerases α, δ and ε, and by the normal replication process on the lagging strand, which uses RNA primers. These ribonucleotides are efficiently removed during replication by RNase H enzymes and the lagging strand synthesis machinery. However, when ribonucleotides remain in DNA they can distort the DNA helix, affect machineries for DNA replication, transcription and repair, and can stimulate genomic instabilities which are manifest as increased mutation, recombination and chromosome alterations. The genomic instabilities associated with embedded ribonucleotides are considered here, along with a discussion of the origin of the lesions that stimulate particular classes of instabilities.



http://ift.tt/2rJKfT8

Value of diagnostic imaging for the symptomatic male breast: Can we avoid unnecessary biopsies?

Publication date: Available online 9 June 2017
Source:Clinical Imaging
Author(s): Eric T. Foo, Amie Y. Lee, Kimberly M. Ray, Genevieve A. Woodard, Rita I. Freimanis, Bonnie N. Joe
PurposeTo review the use of diagnostic breast imaging and outcomes for symptomatic male patients.MethodsWe retrospectively evaluated 122 males who underwent diagnostic imaging for breast symptoms at our academic center.ResultsThe majority (94%) of cases had negative or benign imaging, with gynecomastia being the most common diagnosis (78%). There were two malignancies, both of which had positive imaging. Fifteen patients underwent percutaneous biopsy, and over half (53%) were palpation-guided biopsies initiated by the referring clinician despite negative imaging. Diagnostic imaging demonstrated 100% sensitivity and 96% specificity for identifying cancer.ConclusionsMalignancy is rarely a cause of male breast symptoms. Diagnostic breast imaging is useful to establish benignity and avert unnecessary biopsies.



http://ift.tt/2relbQx

VEGF protein expression is associated with a poor prognosis in cutaneous extranodal NK/T-cell lymphoma patients

Abstract

Vascular endothelial growth factor (VEGF) can stimulate angiogenesis and lymphangiogenesis, which are crucial processes in the growth and metastasis of tumour cells.^1,2 The immunohistochemical status of VEGF protein expression in tumour tissue of extranodal NK/T-cell lymphoma (ENKTL) has not yet been evaluated. Herein, we investigated VEGF protein expression, as well as its prognostic value in cutaneous ENKTL patients.

This article is protected by copyright. All rights reserved.

http://ift.tt/2rJPIcw

Coexistence of EphB1 and EphrinB2 in Port Wine Stain Endothelial Progenitor Cells Contributes to Clinicopathological Vasculature Dilatation

Abstract

Port wine stain (PWS) is a vascular malformation characterized by a progressive dilatation of post-capillary venules, but the molecular pathogenesis remains obscure. We hypothesized that PWS endothelial cells (ECs) present a unique molecular phenotype that lead to pathoanatomic PWS vasculatures. We herein show multiple clinicopathologic features of PWS blood vessels during the development and progression of the disease. 1) There were no normal arterioles and venules phenotypically and morphologically observed in PWS skin; both arterioles and venules showed differentiation impairments, resulting in a reduction of arteriole-like vasculatures and defects in capillary loop formation in PWS lesions. 2) PWS ECs showed stemness properties with expression of endothelial progenitor cell markers CD133 and CD166. They also expressed dual venous/arterial identities, EphB1 and ephrinB2. 3) Co-expression of EphB1 and ephrinB2 in normal human dermal microvascular ECs led to formation of PWS-like vasculatures in vitro, e.g. larger diameter and thick-wall capillaries. We concluded that PWS ECs are differentiation-impaired late stage endothelial progenitor cells with a specific phenotype of CD133⁺/CD166⁺/ EphB1⁺/ephrinB2⁺ which form immature venule-like pathoanatomic vasculatures. The disruption of normal EC-EC interactions by co-existence of EphB1 and ephrinB2 contributes to progressive dilatation of PWS vasculatures.

This article is protected by copyright. All rights reserved.

http://ift.tt/2reoMxT

Dr. Isabelle Rapin

Publication date: Available online 9 June 2017
Source:Brain and Development





http://ift.tt/2re7ukI

The social organization of Homo ergaster: Inferences from anti-predator responses in extant primates

Publication date: August 2017
Source:Journal of Human Evolution, Volume 109
Author(s): Erik P. Willems, Carel P. van Schaik
Patterns of primate socioecology have been used to suggest that the first truly savanna-dwelling hominin, Homo ergaster, lived in sizeable groups. Here, we revisit these estimates and infer additional features of the social organization of these early hominins based on anti-predator responses observed across the primate taxon. We first show that the effect of habitat on primate group size, composition, and sexual dimorphism is negligible after controlling for substrate use and phylogeny: terrestrial species live in larger groups with more and bigger males than arboreal taxa. We next hypothesize that groups can only survive in open habitats if males are able to engage in joint counter-attacks against the large carnivorans typical of such environments. To test this, we analyze reports on primate counter-attacks against known predators and find these are indeed disproportionately frequent in terrestrial taxa living in open habitats, sometimes even involving the use of tentative weapons. If we subsequently only examine the taxa that are particularly adept at this (chimpanzees and baboons), we find an effect of habitat type on group size: groups on the savanna are larger than those in the forest. We thus infer that H. ergaster lived in very large groups with many males that jointly defended the group against carnivorans, and argue that these counter-attacks will readily have turned into confrontational scavenging and cooperative hunting, allowing Homo to move into the niche of social carnivore. These two features (life in very large multi-male groups and a switch to persistent carnivory) shaped the evolution of our lineage to such an extent that the social organization of H. ergaster may already have contained many key elements characterizing modern day foragers: male bonding, incipient male–female friendships with food sharing, a tendency toward endogamy, and the presence of large communities that eventually turned into the ethno-linguistic units we can still recognize today.



http://ift.tt/2sL7gU8

Comment on “Ecological niche of Neanderthals from Spy Cave revealed by nitrogen isotopes of individual amino acids in collagen” [J. Hum. Evol. 93 (2016) 82–90]

Publication date: Available online 8 June 2017
Source:Journal of Human Evolution
Author(s): Tamsin C. O'Connell, Matthew J. Collins




http://ift.tt/2sbzsCk

Data on Leptospira interrogans sv Pomona infection in Meat Workers in New Zealand

Publication date: Available online 8 June 2017
Source:Data in Brief
Author(s): M. Pittavino, A. Dreyfus, C. Heuer, J. Benschop, P. Wilson, J. Collins-Emerson, P.R. Torgerson, R. Furrer
The data presented in this article are related to the research article entitled"Comparison between Generalized Linear Modelling and Additive Bayesian Network; Identification of Factors associated with the Incidence of Antibodies against Leptospira interrogans sv Pomona in Meat Workers in New Zealand" (Pittavino et al., 2017) [5].A prospective cohort study was conducted in four sheep slaughtering abattoirs in New Zealand (NZ) [1]. Sera were collected twice a year from 384 meat workers and tested by Microscopic Agglutination for Leptospira interrogans sv Pomona (Pomona) infection, one of the most common Leptospira serovars in humans in NZ. This article provides an extended analysis of the data, illustrating the different steps of a multivariable (i.e. generalized linear model) and especially a multivariate tool based on additive Bayesian networks (ABN) modelling.



http://ift.tt/2rJjtKj

Computed Tomography Detected Paleopathologies in Ancient Egypt

Publication date: Available online 8 June 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Lara Cramer, Anke Brix, Ekatrina Matin, Frank Rühli, Kais Hussein
Computed tomography (CT)-based analyses of mummies have been performed since the 1970s but, until now, no systematic summary of PubMed® published data has been performed.The aim was to perform a systematic review of previously published cases and summarize artificial changes and detectable paleopathologies.Data collection from publications on CT analyses of mummies from ancient Egypt until the Greco-Roman time period (up to 700 AD) from the PubMed® data base (1973–2013) and descriptive data analysis.Forty-seven publications on CT-based analyses have been identified, which reported on 189 mummies.Commonly reported artificial changes were destruction of the nasal bone and left-sided lateral abdominal incision for removal of inner organs.Dental and jaw pathologies (n=42), chronic degenerative changes of skeletal bones (n=39) and arteriosclerosis (n=36) were reported in a subfraction of cases while traumatic fractures (n=16) and other diseases were less often identified.The cause of death was rarely detectable by CT, but a cut through the throat, arrow heads and bone fracture could be verified by CT.Standards in documentation and CT devices changed during the last 40 years and insufficient documentation limits the interpretation of findings. In ancient Egyptian mummies most organs have been removed during the mummification process while teeth and jaws are often preserved. Dental pathologies were frequent in ancient Egypt and can indicate personal circumstances and diet. The cause of death is rarely verifiable, but CT scan could be the clue. Although well known in Egyptian mummies, artificial changes may lead to misinterpretation of CT findings.



http://ift.tt/2s4Hlsv

Fungal aerocontamination exposure risk for patients in 3 successive locations of a pediatric hematology unit department: Influence of air equipment and building structure on air quality

Publication date: Available online 8 June 2017
Source:American Journal of Infection Control
Author(s): Anne-Pauline Bellanger, Gabriel Reboux, Florent Demonmerot, Houssein Gbaguidi-Haore, Laurence Millon
BackgroundInvasive fungal infections (IFIs) play an important role in the mortality of immunocompromised patients. The pediatric hematology department (PHD) at Besançon University Hospital has relocated 3 times: (1) from a building without an air filtration system (B1), (2) to a renovated building with low air pressure (B2), and (3) to a new building with high air pressure and high-efficiency particulate air filters (B3). This study aimed to investigate how these relocations influenced the fungal exposure risk for the PHD's patients.MethodsAir samples were taken monthly in patient rooms and weekly in corridors. The detection of opportunistic fungi species was used to assess IFI risk. Data were analyzed using univariate and multivariate random-effects negative binomial regression.ResultsA total of 1,074 samples from 29 rooms over a 10-year period showed that renovation of an old building with a basic ventilation system did not lead to a significant improvement of air quality (P = .004, multivariate analysis). Among factors linked to higher risk of patient rooms mold contamination was fungal contamination of the corridors (P < .001).ConclusionsThis study demonstrates that corridors can be used as reliable sentinel to prevent fungal contamination in patient rooms. Only relocation in building B3, equipped with laminar air flow, achieved adequate air quality.



http://ift.tt/2sbFqDr

Impact of an electronic sepsis initiative on antibiotic use and health care facility–onset Clostridium difficile infection rates

Publication date: Available online 8 June 2017
Source:American Journal of Infection Control
Author(s): Robert Hiensch, Jashvant Poeran, Patricia Saunders-Hao, Victoria Adams, Charles A. Powell, Allison Glasser, Madhu Mazumdar, Gopi Patel
BackgroundAlthough integrated, electronic sepsis screening and treatment protocols are thought to improve patient outcomes, less is known about their unintended consequences. We aimed to determine if the introduction of a sepsis initiative coincided with increases in broad-spectrum antibiotic use and health care facility–onset (HCFO) Clostridium difficile infection (CDI) rates.MethodsWe used interrupted time series data from a large, tertiary, urban academic medical center including all adult inpatients on 4 medicine wards (June 2011-July 2014). The main exposure was implementation of the sepsis screening program; the main outcomes were the use of broad-spectrum antibiotics (including 3 that were part of an order set designed for the sepsis initiative) and HCFO CDI rates. Segmented regression analyses compared outcomes in 3 time segments: before (11 months), during (14 months), and after (12 months) implementation of a sepsis initiative.ResultsAntibiotic use and HFCO CDI rates increased during the period of implementation and the period after implementation compared with baseline; these increases were highest in the period after implementation (level change, 50.4 days of therapy per 1,000 patient days for overall antibiotic use and 10.8 HCFO CDIs per 10,000 patient days; P < .05). Remarkably, the main drivers of overall antibiotic use were not those included in the sepsis order set.ConclusionsThe implementation of an electronic sepsis screening and treatment protocol coincided with increased broad-spectrum antibiotic use and HCFO CDIs. Because these protocols are increasingly used, further study of their unintended consequences is warranted.



http://ift.tt/2sLdfZ6

Alcohol fixation of bacteria to surgical instruments increases cleaning difficulty and may contribute to sterilization inefficacy

Publication date: Available online 8 June 2017
Source:American Journal of Infection Control
Author(s): Dayane de Melo Costa, Lillian Kelly de Oliveira Lopes, Honghua Hu, Anaclara Ferreira Veiga Tipple, Karen Vickery
BackgroundAlcohol is frequently inappropriately used on surgical instruments to reduce bacterial contamination, but fixes protein to stainless steel. Here we compare the effect of air drying, prolonged soaking in water, and alcohol treatment on cleaning difficulty of contaminated forceps.MethodsHaltsted-mosquito forceps were contaminated with only Staphylococcus aureus. Instruments were air-dried for 10 (control), 75, or 240 minutes, soaked in water, or air dried then treated with ethanol or isopropanol for 10 seconds. All instruments were prewashed for 15 minutes. Forceps contaminated with blood and S aureus or Pseudomonas aeruginosa were dried and then sprayed or wiped with ethanol, and prewashed. Bacterial viability and soiling were determined by standard plate culture and crystal violet staining, respectively.ResultsSoaking or spraying instruments with alcohol significantly reduced viable bacterial numbers, but significantly increased soil attached to forceps, as did air drying. Wiping instruments with alcohol had little effect on bacterial viability, but increased cleaning difficulty. Soaking in water for 75 or 240 minutes increased cleaning difficulty perhaps due to bacterial attachment to forceps.ConclusionsTreating contaminated instruments with alcohol, allowing them to dry, or allowing them to soak in water for prolonged periods increases cleaning difficulty and should be discouraged.



http://ift.tt/2sbJfID

Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development

Publication date: Available online 8 June 2017
Source:Developmental Cell
Author(s): Benjamin P. Weaver, Yi M. Weaver, Shohei Mitani, Min Han
Recent findings suggest that components of the classical cell death machinery also have important non-cell-death (non-apoptotic) functions in flies, nematodes, and mammals. However, the mechanisms for non-canonical caspase substrate recognition and proteolysis, and the direct roles for caspases in gene expression regulation, remain largely unclear. Here we report that CED-3 caspase and the Arg/N-end rule pathway cooperate to inactivate the LIN-28 pluripotency factor in seam cells, a stem-like cell type in Caenorhabditis elegans, thereby ensuring proper temporal cell fate patterning. Importantly, the caspase and the E3 ligase execute this function in a non-additive manner. We show that CED-3 caspase and the E3 ubiquitin ligase UBR-1 form a complex that couples their in vivo activities, allowing for recognition and rapid degradation of LIN-28 and thus facilitating a switch in developmental programs. The interdependence of these proteolytic activities provides a paradigm for non-apoptotic caspase-mediated protein inactivation.

Graphical abstract

Teaser

The C. elegans caspase CED-3 cleaves the LIN-28 protein to limit its activity during seam cell patterning. Weaver et al. show that this non-apoptotic function of CED-3 occurs in collaboration with a ligase of the Arg/N-end rule pathway, and both proteins are required for efficient recognition and degradation of LIN-28.


http://ift.tt/2r3ogne

Efficacy of Bacillus amyloliquefaciens as biocontrol agent to fight fungal diseases of maize under tropical climates: from lab to field assays in south Kivu

Abstract

In the province of South Kivu (Democratic Republic of Congo), warm and humid climatic conditions favor the development and spreading of phytopathogens. The resulting diseases cause important losses in production both in crop and after harvest. In this study, we wanted to evaluate the potential of Bacillus amyloliquefaciens as biocontrol agent to fight some newly isolated endemic fungal pathogens infesting maize. The strain S499 has been selected based on its high in vitro antagonistic activity correlating with a huge potential to secrete fungitoxic lipopeptides upon feeding on maize root exudates. Biocontrol activity of S499 was further tested on infected plantlets in growth chamber and on plants grown under field conditions over an entire cropping period. We observed a strong protective effect of this strain evaluated at two different locations with specific agro-ecological conditions. Interestingly, disease protection was associated with higher yields and our data strongly suggest that, in addition to directly inhibit pathogens, the strain may also act as biofertilizer through the solubilization of phosphorus and/or by producing plant growth hormones in the rhizosphere. This work supports the hope of exploiting such technologically advantageous bacilli for the sake of sustainable local production of this important crop in central Africa.

http://ift.tt/2t2SCqy

Increased FDG uptake on late-treatment PET in non-tumour-affected oesophagus is prognostic for pathological complete response and disease recurrence in patients undergoing neoadjuvant radiochemotherapy

Abstract

Purpose

Early side effects including oesophagitis are potential prognostic factors in patients undergoing radiochemotherapy (RCT) for locally advanced oesophageal cancer (LAEC). We assessed the prognostic value of ¹⁸F-fluorodeoxyglucose (FDG) uptake within irradiated non-tumour-affected oesophagus (NTO) during restaging positron emission tomography (PET) as a surrogate for inflammation/oesophagitis.

Methods

This retrospective evaluation included 64 patients with LAEC who had completed neoadjuvant RCT and had successful oncological resection. All patients underwent FDG PET/CT before and after RCT. In the restaging PET scan maximum and mean standardized uptake values (SUV_max, SUV_mean) were determined in the tumour and NTO. Univariate Cox regression with respect to overall survival, local control, distant metastases and treatment failure was performed. Independence of clinically relevant parameters was tested in a multivariate Cox regression analysis.

Results

Increased FDG uptake, measured in terms of SUV_mean in NTO during restaging was significantly associated with complete pathological remission (p = 0.002) and did not show a high correlation with FDG response of the tumour (rho < 0.3). In the univariate analysis, increased SUV_max and SUV_mean in NTO was associated with improved overall survival (p = 0.011, p = 0.004), better local control (p = 0.051, p = 0.044), a lower rate of treatment failure (p < 0.001 for both) and development of distant metastases (p = 0.012, p = 0.001). In the multivariate analysis, SUV_max and SUV_mean in NTO remained a significant prognostic factor for treatment failure (p < 0.001, p = 0.004) and distant metastases (p = 0.040, p = 0.011).

Conclusions

FDG uptake in irradiated normal tissues measured on restaging PET has significant prognostic value in patients undergoing neoadjuvant RCT for LAEC. This effect may potentially be of use in treatment personalization.

http://ift.tt/2t2Karc

Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia

Publication date: Available online 8 June 2017
Source:Journal of Genetics and Genomics
Author(s): Jinsong Tang, Yu Fan, Hong Li, Qun Xiang, Deng-Feng Zhang, Zongchang Li, Ying He, Yanhui Liao, Ya Wang, Fan He, Fengyu Zhang, Yin Yao Shugart, Chunyu Liu, Yanqing Tang, Raymond C.K. Chan, Chuan-Yue Wang, Yong-Gang Yao, Xiaogang Chen
Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive. We implemented whole-genome sequencing (WGS) analysis of 8 families with monozygotic (MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations (DNMs) or inherited variants with susceptibility to schizophrenia. Eight nonsynonymous DNMs (including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes (p.V24689I mutation in TTN, p.S2506T mutation in GCN1L1, IVS3+1G>T in DOCK1) or have a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function (LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations (CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.



http://ift.tt/2rJ8kZW

Dual-Energy Computed Tomography Angiography of the Head and Neck and Related Applications

Publication date: Available online 8 June 2017
Source:Neuroimaging Clinics of North America
Author(s): Shahmir Kamalian, Michael H. Lev, Stuart R. Pomerantz

Teaser

Dual-energy computed tomography (DECT) has become an increasingly widespread and useful component of the neuroimaging armamentarium, offering automated bone removal, metallic artifact reduction, and improved characterization of iodinated contrast enhancement. The application of these techniques to CT neuroangiography enables a number of benefits including more efficient 3D post-processing, contrast dose reduction opportunities, successful differentiation of hemorrhage from contrast staining following thromboembolic recanalization therapy, improved detection of active contrast extravasation in the setting of intracranial hemorrhage, and more precise characterization of atheromatous steno-occlusive disease.


http://ift.tt/2rdEMAg